Using Augmented Mean Arterial Pressure to Identify High Mortality Risk Patients With Moderate Aortic Stenosis.
Mayo Clinic proceedings
OBJECTIVE:To study the usefulness of a novel echocardiographic marker, augmented mean arterial pressure (AugMAP = [(mean aortic valve gradient + systolic blood pressure) + (2 × diastolic blood pressure)] / 3), in identifying high-risk patients with moderate aortic stenosis (AS). PATIENTS AND METHODS:Adults with moderate AS (aortic valve area, 1.0-1.5 cm) at Mayo Clinic sites from January 1, 2010, through December 31, 2020, were identified. Baseline demographic, echocardiographic, and all-cause mortality data were retrieved. Patients were grouped into higher and lower AugMAP groups using a cutoff value of 80 mm Hg for analysis. Kaplan-Meier and Cox regression models were used to assess the performance of AugMAP. RESULTS:A total of 4563 patients with moderate AS were included (mean ± SD age, 73.7±12.5 years; 60.5% men). Median follow-up was 2.5 years; 36.0% of patients died. The mean ± SD left ventricular ejection fraction (LVEF) was 60.1%±11.4%, and the mean ± SD AugMAP was 99.1±13.1 mm Hg. Patients in the lower AugMAP group, with either preserved or reduced LVEF, had significantly worse survival performance (all P<.001). Multivariate Cox regression showed that AugMAP (hazard ratio, 0.962; 95% CI, 0.942 to 0.981 per 5-mm Hg increase; P<.001) and AugMAP less than 80 mm Hg (hazard ratio, 1.477; 95% CI, 1.241 to 1.756; P<.001) were independently associated with all-cause mortality. CONCLUSION:AugMAP is a simple and effective echocardiographic marker to identify high-risk patients with moderate AS independent of LVEF. It can potentially be used in the candidate selection process if moderate AS becomes indicated for aortic valve intervention in the future.
10.1016/j.mayocp.2023.02.028
The influence of mean arterial pressure on the efficacy and safety of dual antiplatelet therapy in minor stroke or transient ischemic attack patients.
Ma Yan,Liu Ying,Xu Jie,Wang Yilong,Du Fenghe,Wang Yongjun
Journal of clinical hypertension (Greenwich, Conn.)
Mean arterial pressure (MAP) is the strongest predictor of stroke. The combination of clopidogrel and aspirin within 24 hours after onset has been suggested by the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) study to be superior to aspirin alone. However, it is not clear whether poststroke blood pressure has an influence on the efficacy and safety of dual antiplatelet treatment. We have performed a post hoc analysis from the CHANCE trial. Patients were stratified into three groups based on MAP levels. Among patients with MAP <102 mm Hg, there was no significant difference in stroke recurrence between the clopidogrel-aspirin group and the aspirin group (7.7% vs 7.5%; hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.73-1.45). However, compared to aspirin treatment, the clopidogrel-aspirin dual treatment was more effective at reducing the risk of stroke in patients with MAP ≥113 mm Hg (6.9% vs 12.3%, HR, 0.55; 95% CI, 0.39-0.78) or 102-113 mm Hg (9.5% vs 14.9%, HR, 0.62; 95% CI, 0.48-0.81). There was a significant interaction between MAP and antiplatelet therapy as it relates to stroke recurrence (P for interaction = 0.037), and a similar result was found for combined vascular events (P for interaction = 0.027). In conclusion, dual antiplatelet therapy may be more effective at reducing combined vascular events in patients with higher MAP after minor stroke or transient ischemic attack.
10.1111/jch.13527
The dynamics of blood pressure of different age patients groups with hypertension and diabetes type ii after correction of carotid stenosis.
Kobza Igor I,Didenko Oksana Z,Yavorskyi Ostap G,Kobza Тaras I
Wiadomosci lekarskie (Warsaw, Poland : 1960)
OBJECTIVE:Introduction: hypertension and diabetes remain the main risk factors for stroke, which leads to premature disability and mortality. The aim: To study the dynamics of blood pressure (BP) in patients of different age groups with hypertension and diabetes type II before and after carotid endarterectomy. PATIENTS AND METHODS:Materials and methods: 90 patients with hypertension and diabetes type II were selected for CE. Patients are divided into two age groups: up to 65 years (group 1) and after 65 years (group 2). We assessed the dynamics of ambulatory blood pressure monitoring (ABPM). The examination was carried out 2 days before and 6 months after surgery. CE was conducted under local anaesthesia. RESULTS:Results: Before operation in patients in group 2, there was a significantly higher level of average systolic BP per 24 hours (p <0.02), per day (p <0.01), per night (p <0.01) and diastolic BP per night (p <0,01). At the preoperative stage, there was a significant increase in the parameters of the variability of BP, but the increase in the variability of BP with age was not fixed. After surgery, patients with Group 1 observed a more significant positive dynamics of ABPM indices than patients in Group 2. In two age groups, the percentage of patients with an insufficient reduction of BP at night was prevalent. CONCLUSION:Conclusions: Surgical treatment of carotid stenosis is associated with a steady decrease in BP in the distant period after CE. Significant regression of BP is characteristic for patients of the younger age group.
A 10% blood pressure drop from baseline during mechanical thrombectomy for stroke is strongly associated with worse neurological outcomes.
Valent Arnaud,Sajadhoussen Amard,Maier Benjamin,Lapergue Bertrand,Labeyrie Marc-Antoine,Reiner Peggy,Consoli Arturo,Fischler Marc,Gayat Etienne,Leguen Morgan
Journal of neurointerventional surgery
BACKGROUND:Mechanical thrombectomy (MT) for acute ischemic stroke can be performed under local anesthesia, with or without conscious sedation (CS), or under general anesthesia (GA). The hemodynamic consequence of anesthetic drugs may explain why GA may be associated with worse outcomes. We evaluated the association between hypotension duration during MT and the 90 day functional outcome under both anesthetic regimens. METHODS:Patients were included in this retrospective study if they had an ischemic stroke treated by MT under GA or CS. The main exposure variable was the time below 90% of the reference value of arterial pressure measured before MT. The primary outcome was poor functional outcome defined as a 90 day modified Rankin Score ≥3. RESULTS:371 patients were included in the study. GA was performed in 42%. A linear association between the duration of arterial hypotension and outcome was observed. The odds ratio for poor functional outcome of 10 min under 90% of the baseline mean arterial pressure was 1.13 (95% CI 1.06 to 1.21) without adjustment and 1.11 (95% CI 1.02 to 1.21) after adjustment for confounding factors. The functional outcome was poorer for patients treated under GA compared with CS, but the association with the depth of hypotension remained similar under both conditions. CONCLUSION:In this study, we observed a linear association between the duration of hypotension during MT and the functional outcome at 90 days. An aggressive and personalized strategy for the treatment of hypotension should be considered. Further trials should be conducted to address this question.
10.1136/neurintsurg-2019-015247
Increased blood pressure variability during the subacute phase in patients with ischemic stroke presenting with a low ankle-brachial index.
Naito Hiroyuki,Hosomi Naohisa,Kuzume Daisuke,Nezu Tomohisa,Aoki Shiro,Morimoto Yuko,Kinboshi Masato,Yoshida Takeshi,Shiga Yuji,Kinoshita Naoto,Ueno Hiroki,Noma Kensuke,Maruyama Hirofumi
Geriatrics & gerontology international
AIM:This study aimed to evaluate the associations of blood pressure (BP) variability in patients with ischemic stroke during the subacute phase using ambulatory blood pressure monitoring and the ankle-brachial index (ABI). METHODS:We retrospectively examined 831 consecutive patients (women 44.8%, mean age 76 ± 12 years) with acute ischemic stroke who underwent 24-h ambulatory blood pressure monitoring during the subacute phase of stroke (median 9 days from onset) and an ABI examination. BP variability was evaluated by assessing the standard deviation and coefficient of variation of systolic BP and diastolic BP. A low ABI was defined as an ABI <0.9. RESULTS:Of the 831 patients, 201 (24.2%) had a low ABI. Older age, lower body mass index, diabetes mellitus, chronic kidney disease, atrial fibrillation and a higher National Institutes of Health Stroke Scale score at admission were independently associated with a low ABI. The patients with a low ABI had a higher mean 24-h diastolic BP, higher standard deviation of both BP measurements (systolic BP and diastolic BP) and a higher coefficient of variation in both BP measurements than those with a higher ABI. According to the multivariable linear regression analysis, a low ABI was independently associated with increased BP variability (a high standard deviation or coefficient of variation of both BP measurements) after adjusting for baseline confounders. CONCLUSIONS:A low ABI was associated with increased BP variability during the subacute ischemic phase. Geriatr Gerontol Int 2020; 20: 448-454.
10.1111/ggi.13897
Increased blood pressure variability during the subacute phase of ischemic stroke is associated with poor functional outcomes at 3 months.
Naito Hiroyuki,Hosomi Naohisa,Kuzume Daisuke,Nezu Tomohisa,Aoki Shiro,Morimoto Yuko,Kinboshi Masato,Yoshida Takeshi,Shiga Yuji,Kinoshita Naoto,Ueno Hiroki,Noma Kensuke,Yamasaki Masahiro,Maruyama Hirofumi
Scientific reports
Thus far, it is well known that increased blood pressure variability may exacerbate stroke outcomes. Blood pressure in the acute phase would be influenced by both reactive hypertension to stroke and intrinsic blood pressure reactivity. Thus, we aimed to evaluate the association between blood pressure variability and outcomes at 3 months using ambulatory blood pressure monitoring in ischemic stroke patients in the subacute phase after reactive hypertension subsided. We retrospectively examined 626 consecutive patients with acute ischemic stroke who underwent 24-hour ambulatory blood pressure monitoring during the subacute phase of stroke (median, 9 days from onset). The variability in blood pressure was evaluated by assessing the standard deviation and coefficient of variation of systolic and diastolic blood pressure. The primary outcome was functional status at 3 months. A poor outcome was defined as a modified Rankin scale score of 3 or more and a good outcome as 2 or less. We assessed the functional outcome at 3 months in 497 patients (79.4%). The mean systolic and diastolic blood pressure levels were not associated with functional outcome. The multivariable analysis revealed that increases in the standard deviations of systolic and diastolic blood pressure, coefficient of variation of diastolic blood pressure, and morning blood pressure surge were associated with poor outcome. Blood pressure variability during the subacute phase of ischemic stroke can be a useful prognostic indicator of poor functional outcome at 3 months in patients with acute ischemic stroke.
10.1038/s41598-020-57661-z
Determinants of the high admission blood pressure in mild-to-moderate acute intracerebral hemorrhage.
Wang Xia,Sandset Else C,Moullaali Tom J,Chen Guojuan,Song Lily,Carcel Cheryl,Delcourt Candice,Woodward Mark,Robinson Thompson,Chalmers John,Arima Hisatomi,Anderson Craig S,
Journal of hypertension
BACKGROUND AND PURPOSE:An early elevation in blood pressure (BP) is common after spontaneous intracerebral hemorrhage (ICH), has various potential causes, and is predictive of poor outcome. We aimed to determine the predictors of this phenomenon, in pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials [INTERACT1 (n = 404) and INTERACT2 (n = 2829)]. METHODS:INTERACT trials were international, open, blinded endpoint, randomized controlled trials of patients with spontaneous ICH (<6 h) and elevated SBP (150-220 mmHg) assigned to intensive (target SBP < 140 mmHg) or guideline-recommended (SBP < 180 mmHg) treatment. Multivariable linear and logistic regression models were used to determine associations between baseline variables and the high admission BP, with continuous and binary SBP measures, respectively. RESULTS:Among 3233 patients (mean age 63 years; 37% female; baseline mean SBP 179 mmHg), both analytic approaches showed significant positive associations of high admission BP with history of hypertension, admission hyperglycemia at least 6.5 mmol/l, elevated heart rate, and greater neurological severity (National Institutes of Health Stroke Scale scores); and significant negative associations with prior use of antithrombotic agents and longer time from onset to randomization. CONCLUSION:The high admission BP of mild-to-moderate acute ICH is related to autonomic nervous system activated 'stress' rather than hematoma location and mass effect. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.
10.1097/HJH.0000000000002056
Blood Pressure measurements are site dependent in a cohort of patients with neurological illness.
Siaron Kathrina B,Cortes Michaela X,Stutzman Sonja E,Venkatachalam Aardhra,Ahmed Khalid Mohamed,Olson DaiWai M
Scientific reports
Blood pressure (BP) management is a crucial part of critical care that directly affects morbidity and mortality. While BP has become a mainstay in patient care, the accuracy and precision of BP measures across commonly used sites (left upper arm, right upper arm, etc.) and methods have not been established. This study begins to fill this gap in literature by testing the null hypothesis that BP measurement does not vary according to site. This is a prospective, non-randomized, cross-sectional study of 80 neurocritical care unit patients. Near simultaneous non-invasive blood pressure (NIBP) readings from 4 different locations (bilateral upper arm, bilateral wrist) and, when available, intra-arterial blood pressure readings (IABP) were included. Pearson correlation coefficients and one-way repeated measures ANOVA were used to observe the systolic, diastolic, and mean arterial pressure (MAP) correlations. The BP measured at the four most common sites (left upper arm, left wrist, right upper arm, right wrist) had adequate correlation coefficients but were statistically significantly different and highly unpredictable. The median inter-site systolic variability was 10 mmHg (IQR 2 to 10 mmHg). The median inter-site MAP variability was 6mmHg with an interquartile range (IQR) of 3 to 9 mmHg. As expected, the values correlated to show that patients with high BP in one site tended to have high BP in another site. However, the unpredictable inter-site variability is concerning within the clinical setting where oftentimes BP measurement site is not standardized but resulting values are nevertheless used for treatment. There is prominent inter-site variability of BP measured across the 4 most common measurement sites. The variability persists across non-invasive (NIBP) and invasive (IABP) methods of assessment.
10.1038/s41598-020-60414-7
Long-term systolic blood pressure variability independent of mean blood pressure is associated with mortality and cardiovascular events: A systematic review and meta-analysis.
Current problems in cardiology
The association between long-term systolic blood pressure variability (SBPV) and cardiovascular (CV) outcomes after being adjusted with mean blood pressure (BP) is questionable. This systematic review aims to evaluate the associations between mean BP adjusted long-term SBPV and CV outcomes. A systematic search was conducted on PubMed, Scopus, and Science Direct on January 4, 2023. A total of 9,944,254 subjects from 43 studies were included in this meta-analysis. Long-term SBPV increased the risk of all-cause mortality (HR 1.21 [95%CI 1.16-1.25], I=100%), CV mortality (HR 1.10 [95%CI 1.07-11.4], I2 = 90%), MACE (HR 1.10 [1.07-1.13], I = 91%), cerebrovascular stroke (HR 1.22 [1.16-1.29], I=100%), and myocardial infarction (HR 1.13 [95%CI (1.07-1.19)], I=91%). European populations generally had higher risk compared to other continents. In conclusion, long-term SBPV is associated with all-cause mortality, CV mortality, MACE, MI, and stroke. Poor outcomes related to long-term SBPV seem more dominated by cerebrovascular than coronary events.
10.1016/j.cpcardiol.2023.102343
Aerobic exercise interventions reduce blood pressure in patients after stroke or transient ischaemic attack: a systematic review and meta-analysis.
British journal of sports medicine
OBJECTIVE:Secondary vascular risk reduction is critical to preventing recurrent stroke. We aimed to evaluate the effect of exercise interventions on vascular risk factors and recurrent ischaemic events after stroke or transient ischaemic attack (TIA). DESIGN:Intervention systematic review and meta-analysis. DATA SOURCES:OVID MEDLINE, PubMed, The Cochrane Library, Web of Science, The National Institute for Health and Care Excellence, TRIP Database, CINAHL, PsycINFO, SCOPUS, UK Clinical Trials Gateway and the China National Knowledge Infrastructure were searched from 1966 to October 2017. ELIGIBILITY CRITERIA:Randomised controlled trials evaluating aerobic or resistance exercise interventions on vascular risk factors and recurrent ischaemic events among patients with stroke or TIA, compared with control. RESULTS:Twenty studies (n=1031) were included. Exercise interventions resulted in significant reductions in systolic blood pressure (SBP) -4.30 mm Hg (95% CI -6.77 to -1.83) and diastolic blood pressure -2.58 mm Hg (95% CI -4.7 to -0.46) compared with control. Reduction in SBP was most pronounced among studies initiating exercise within 6 months of stroke or TIA (-8.46 mm Hg, 95% CI -12.18 to -4.75 vs -2.33 mm Hg, 95% CI -3.94 to -0.72), and in those incorporating an educational component (-7.81 mm Hg, 95% CI -14.34 to -1.28 vs -2.78 mm Hg, 95% CI -4.33 to -1.23). Exercise was also associated with reductions in total cholesterol (-0.27 mmol/L, 95% CI -0.54 to 0.00), but not fasting glucose or body mass index. One trial reported reductions in secondary vascular events with exercise, but was insufficiently powered. SUMMARY:Exercise interventions can result in clinically meaningful blood pressure reductions, particularly if initiated early and alongside education.
10.1136/bjsports-2017-098903
Effect of Intensive Blood Pressure Control on Incident Stroke Risk in Patients With Mild Cognitive Impairment.
Stroke
BACKGROUND:Patients with mild cognitive impairment may be at higher risk of incident stroke, but the effect of intensive blood pressure (BP) control on that risk has not been explored. METHODS:We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) and included patients with a baseline Montreal Cognitive Assessment score of 19 to 25 and without a prior history of stroke. The primary outcome was incident stroke (ischemic and hemorrhagic) during follow-up. We report the unadjusted cumulative risk of our primary outcome by SPRINT randomization arm (intensive versus standard BP control) and also fit Cox models to the primary outcome and adjusted for patient age at randomization, race/ethnicity, sex, baseline BP, atrial fibrillation, diabetes, and smoking. RESULTS:We included 5091 patients (mean age 68.2, 44% female, 56.7% non-Hispanic White, and 50.2% randomized to intensive BP control), of which 95/5091 (1.9%) had an incident stroke during a mean of 3.8±0.9 years of follow-up. The risk of incident stroke in patients randomized to standard BP control was 57/2536 (2.3%) and to intensive BP control was 38/2555 (1.5%; =0.045). In the adjusted Cox model, the hazard ratio for incident stroke events with intensive BP control was 0.65 (95% CI, 0.43-0.98; =0.040). CONCLUSIONS:Although the SPRINT trial failed to show a reduction in stroke with intensive BP control for all subjects, those with a Montreal Cognitive Assessment score consistent with mild cognitive impairment at baseline had an association between intensive BP control and lower risk of incident stroke. Future trials of primary prevention of stroke may benefit from enrichment using baseline vascular biomarkers of elevated risk, such as mild cognitive impairment.
10.1161/STROKEAHA.122.038818
The impact of age and 24-h blood pressure on arterial health in acute ischemic stroke patients: The Norwegian stroke in the young study.
Journal of clinical hypertension (Greenwich, Conn.)
The impact of age and 24-h ambulatory blood pressure (ABPM) on arterial stiffness and carotid intima-media thickness (cIMT) in ischemic stroke patients younger than 60 years of age is poorly explored. A total of 385 acute ischemic stroke patients (aged 49.6±9.7 years, 68% men) were prospectively included and grouped in younger (15-44 years, n = 93) and middle-aged (45-60 years, n = 292). Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV), and cIMT by carotid ultrasound. 24-h ABPM was recorded. The middle-aged stroke patients had higher prevalence of smoking, hypertension, diabetes mellitus, metabolic syndrome and hypercholesterolemia, and had higher PWV and cIMT (all p < .05). In multivariable linear regression analyses adjusted for sex, BMI, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, triglycerides, eGFR, systolic BP and concomitant antihypertensive treatment, 1SD (4.4 years) higher age was associated with higher PWV (β = 0.44,R = 0.46, p < .001) in the younger group, and with higher mean cIMT (β = 0.16, R = 0.21, p = .01) in the middle-aged group. In the middle-aged group, 24-h pulse pressure had a significant association with PWV (β = 0.18, R = 0.19, p = .009), while the association with cIMT was attenuated (β = 0.13, R = 0.16, p = .065). 24-h diastolic BP was associated with higher cIMT in the middle-aged group (β = 0.24, p < .001, R = 0.23), but not with PWV in either age groups. Among ischemic stroke patients < 60 years, higher age was associated with increased arterial stiffness for patients up to age 44 years, and with cIMT in middle-aged patients. 24-h pulse pressure was associated with arterial stiffness, and 24-h diastolic BP was associated with cIMT only in middle-aged patients.
10.1111/jch.14361
FEATURES OF CEREBRAL HEMODYNAMICS IN PATIENTS AFTER STROKE DEPENDING ON THE VARIABILITY OF BLOOD PRESSURE AND THEIR QUALITY OF LIFE.
Wiadomosci lekarskie (Warsaw, Poland : 1960)
OBJECTIVE:The aim: To study cerebral hemodynamics in patients after ischemic stroke (IS) depending on the variability of blood pressure (BP) and to assess the quality of life (QOL). PATIENTS AND METHODS:Materials and methods: The study included 90 patients of SIS «RSCPC» SAD aged 33 to 72 years: The 1st (main) group consisted of 30 patients with ischemic stroke (IS) on the background of hypertension (HTN) with mild neurological deficits; 2nd - 30 patients who have been suffering from HTN for more than 10 years and have manifestations of dyscirculatory encephalopathy of I-II stage.; 3rd group - 30 patients who did not suffer from HTN. RESULTS:Results: Variability of blood pressure in patients with ischemic stroke with mild neurological deficits on the background of hypertension (hypertension) did not differ significantly from that in patients with hypertension with more than 10 years of experience, but their cerebral blood flow rate was significantly lower. Neurological functions, cognitive and psycho-emotional statuses and, as a consequence, quality of life were also significantly worse in patients after stroke. CONCLUSION:Conclusions: cerebral disorders and quality of life in patients after stroke are associated with decreased cerebral blood flow, regardless of the variability of blood pressure.
10.36740/WLek202205106
Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke: multicentre, open label, randomised, controlled trial.
BMJ (Clinical research ed.)
OBJECTIVES:To compared the effect of early antihypertensive treatment started within 24-48 h of stroke onset versus delaying treatment until day eight on reducing dependency or death. DESIGN:Multicentre, randomised, open label trial. SETTING:106 hospitals in China between 13 June 2018 and 10 July 2022. PARTICIPANTS:4810 patients (≥40 years) were enrolled with acute ischaemic stroke within 24-48 h of symptom onset and elevated systolic blood pressure between 140 mm Hg and <220 mm Hg. INTERVENTIONS:Patients were randomly assigned to receive antihypertensive treatment immediately after randomisation (aimed at reducing systolic blood pressure by 10%-20% within the first 24 h and a mean blood pressure <140/90 mm Hg within seven days) or to discontinue antihypertensive medications for seven days if they were taking them, and then receive treatment on day 8 (aimed at achieving mean blood pressure <140/90 mm Hg). MAIN OUTCOME MEASURES:The primary outcome was the combination of functional dependency or death (modified Rankin scale score ≥3) at 90 days. Intention to treat analyses were conducted. RESULTS:2413 patients were assigned to the early treatment group and 2397 were assigned to the delayed treatment group. Mean systolic blood pressure was reduced by 9.7% (from 162.9 mm Hg to 146.4 mm Hg) in the early treatment group and by 4.9% (from 162.8 mm Hg to 154.3 mm Hg) in the delayed treatment group within 24 h after randomisation (P for group difference <0.001). Mean systolic blood pressure was 139.1 mm Hg in the early treatment group and 150.9 mm Hg in the delayed treatment group on day seven (P for group difference <0.001). Additionally, 54.6% of patients in the early treatment group and 22.4% in the delayed treatment group had blood pressure of less than 140/90 mm Hg (P<0.001 for group difference) on day seven. At day 90, 289 trial participants (12.0%) in the early treatment group, compared with 250 (10.5%) in the delayed treatment group, had died or experienced a dependency (odds ratio 1.18 (95% confidence interval 0.98 to 1.41), P=0.08). No significant differences in recurrent stroke or adverse events were reported between the two groups. CONCLUSIONS:Among patients with mild-to-moderate acute ischaemic stroke and systolic blood pressure between 140 mm Hg and <220 mm Hg who did not receive intravenous thrombolytic treatment, early antihypertensive treatment did not reduce the odds of dependency or death at 90 days. TRIAL REGISTRATION:ClinicalTrials.gov Identifier NCT03479554.
10.1136/bmj-2023-076448
Twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke.
Heart (British Cardiac Society)
OBJECTIVE:The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes. METHODS:A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190-170 mm Hg), trajectory category 4 (180-140 mm Hg), trajectory category 3 (170-160 mm Hg), trajectory category 2 (155-145 mm Hg) and trajectory category 1 (150-130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke. RESULTS:Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events. CONCLUSION:Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.
10.1136/heartjnl-2023-323821
Pre-Stroke Antihypertensive Therapy Affects Stroke Severity and 3-Month Outcome of Ischemic MCA-Territory Stroke.
Diseases (Basel, Switzerland)
OBJECTIVES:Whether different antihypertensive drug classes in high blood pressure (HBP) pre-stroke treatment affect dynamic cerebral autoregulation (dCA), stroke severity, and outcome. METHODS:Among 337 consecutive ischemic stroke patients (female 102; median age 71 years [interquartile range, [IQR 60; 78]; NIHSS median 3 [IQR 1; 6]) with assessment of dCA, 183 exhibited the diagnosis of HBP. dCA parameters' gain and phase were determined by transfer function analysis of spontaneous oscillations of blood pressure and cerebral blood flow velocity. RESULTS:Patients used beta-blockers ( = 76), calcium channel blockers (60), diuretics (77), angiotensin-converting enzyme inhibitors (59), or angiotensin-1 receptor blockers (79), mostly in various combinations of two or three drug classes. dCA parameters did not differ between the non-HBP and the different HBP medication groups. Multinomial ordinal logistic regression models revealed that the use of diuretics decreased the likelihood of a less severe stroke (odds ratio 0.691, 95% CI 0.493; 0.972; = 0.01) and that beta-blockers decreased the likelihood of a better modified Rankin score at 3 months (odds ratio 0.981, 95% CI 0.970; 0.992; = 0.009). Other independent factors associated with stroke outcome were penumbra and infarct volume, treatment with mechanical thrombectomy, and the initial National Institute of Health Stroke Scale score. INTERPRETATION:In this cohort of ischemic minor to moderate stroke patients, pre-stroke antihypertensive treatment with diuretics was associated with a more severe neurological deficit on admission and pre-stroke treatment with beta-blockers with a poorer 3-month outcome. The antihypertensive drug class used pre-stroke did not impact dCA.
10.3390/diseases12030053
Relationship between mean blood pressure during hospitalization and clinical outcome after acute ischemic stroke.
BMC neurology
OBJECTIVE:The optimal blood pressure (BP) targets for acute ischemic stroke are unclear. We aimed to assess the relationship between Mean BP and clinical outcomes during hospitalization. MATERIALS AND METHODS:We included 649 patients with Acute ischemic stroke (AIS) from December 2020 to July 2021. BP was measured daily, and mean blood pressure was calculated. Clinical events recorded within 90 days of randomization were: recurrent ischemic stroke, symptomatic intracranial hemorrhage, and death. The modified Rankin Scale (mRS) was used to measure primary outcomes 3 months after AIS. Logistic multiple regression analysis was performed by statistical software R. RESULT:There is a nonlinear U-shaped relationship between SBP and poor outcomes. This means higher SBP and lower SBP will increase the incidence of poor outcomes. The optimal mean SBP during hospitalization was 135-150 mmHg, and patients with SBP < 135mmhg OR 2.4 [95% Cl, (1.16 ~ 4.97)], P = 0.018; and > 150mmhg OR 2.04 [95% Cl, 1.02 ~ 4.08], p = 0.045 had a higher probability of poor outcomes. CONCLUSION:Our study shows that the optimal SBP of patients with AIS during hospitalization was 135-150 mmHg. The findings suggest that the relationship between mean SBP and 3-month functional outcome after AIS was U-shaped. Both higher SBP and lower SBP lead to poor prognosis in AIS patients.
10.1186/s12883-023-03209-3
Association between antihypertensive treatment, blood pressure variability, and stroke severity and outcomes in acute ischemic stroke.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
OBJECTIVES:The management of blood pressure (BP) and the role of antihypertensive medications (AHT) in acute ischemic stroke (AIS) remain uncertain. This study aimed to investigate the impact of pre- and intra-stroke AHT use on systolic (SBP), diastolic (DBP), and blood pressure variability (BPV). MATERIALS AND METHODS:A post-hoc analysis was conducted on 228 AIS patients from the PREVISE study. All patients underwent 24-hour ambulatory blood pressure monitoring within 48 h of symptom onset. Clinical and laboratory data, as well as AHT details, were recorded. Mean BP parameters and BPV for SBP and DBP were computed. The study endpoint was 3-month mortality. RESULTS:The majority of stroke patients (84.2%) were already taking AHTs. Beta blockers and ACE inhibitors use before and after stroke were linked to higher DBP variability. Prior angiotensin receptor blockers (ARBs) and vasodilators use correlated with increased SBP variability and lower daytime SBP/DBP levels, respectively. The continuation, discontinuation, or change of AHTs after stroke onset did not significantly affect outcomes. Patients under AHTs during AIS exhibited reduced mortality, with those previously using calcium channel blockers experiencing less severe strokes, and those previously using ARBs showing better outcomes at three months. CONCLUSIONS:These findings advocate for personalized BP management in AIS, based on a patient's antihypertensive history. These insights could enhance treatment efficacy, guide research, and improve care for acute ischemic stroke patients.
10.1016/j.jocn.2024.05.014
Blood Pressure Fluctuation During Hospitalization and Clinical Outcomes Within 3 Months After Ischemic Stroke.
Hypertension (Dallas, Tex. : 1979)
BACKGROUND:Increased blood pressure (BP) variability is positively associated with the risks of cerebral small-vessel disease, cardiovascular events and death. However, no large clinical trials have been published to demonstrate the effect of BP fluctuations during hospitalization on clinical outcomes after ischemic stroke. METHODS:A total of 3972 patients with acute ischemic stroke from 26 participating hospitals were included in this study, and BP fluctuations were calculated using BP data collected during the hospitalization. The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months and secondary outcomes included death, vascular events, and composite outcomes (death or vascular events). RESULTS:Compared with the lowest quartile of systolic BP fluctuations, the adjusted odds ratio associated with the highest quartile was 1.33 ([95% CI, 1.05-1.68]; =0.011) for primary outcome; the adjusted hazard ratios were 2.89 ([95% CI, 1.58-5.32]; <0.001) for death, 1.48 ([95% CI, 0.83-2.65]; =0.071) for vascular events, and 2.06 ([95% CI, 1.32-3.23]; <0.001) for composite outcome. Similar results were found for diastolic BP. Multivariable adjusted restricted cubic spline analysis showed a linear relationship between systolic BP fluctuations and the primary outcome ( for linearity=0.0009). CONCLUSIONS:Larger BP fluctuations during hospitalization were associated with an increased risk of adverse outcomes at 3 months after ischemic stroke onset, independent of mean BP. These findings suggested that BP fluctuation should be a risk factor of adverse outcomes after ischemic stroke, which provided a new insight for BP management strategy.
10.1161/HYPERTENSIONAHA.122.19629
Focus on blood pressure levels and variability in the early phase of acute ischemic stroke with hypertension and carotid stenosis.
He Mingli,Cui Bing,Wang Jin'e,Xiao Xiao,Wu Taotao,Wang Mingyu,Yang Ru,Zhang Bo,Xu Bingchao,He Xiaobing,Zhang Guanghui,Niu Xiaoqin,Li Zaipo,Wang Bei,Xu Bei,Hui Rutai,Wang Yibo
Journal of clinical hypertension (Greenwich, Conn.)
To investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single-center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP < 140 mm Hg and DBP < 90 mm Hg), Group 2: (SBP: 140-159 mm Hg and or DBP: 90-99 mm Hg), and Group 3: (SBP ≥160 mm Hg and/or DBP ≥100 mm Hg) according to the guidelines. The associations of mean BP levels and variability with outcomes (recurrent stroke, all-cause death and the composite cardiovascular events) at 6 months were analyzed by Cox proportional hazard models. The associations of BP variability with BP levels and cerebral blood flow (CBF) were analyzed by linear regression and generalized additive models. Both for primary and secondary outcome, more events occurred in Group 1 compared with Group 2, while no significant difference was found in Group 3 with higher BP levels. Lower systolic BP variability showed better prognosis and higher CBF. The associations were more significant in patients with CAS ≥50%. BP variability exhibited a linear negative relationship with BP levels. In the early phase of AIS with hypertension and CAS, maintaining low blood pressure variability may be important to improve outcomes while low BP levels (SBP/DBP < 140/90 mm Hg) were harmful, especially in those patients with CAS ≥ 50%.
10.1111/jch.14385
Cerebral hemodynamic effects of early blood pressure lowering after TIA and stroke in patients with carotid stenosis.
International journal of stroke : official journal of the International Stroke Society
BACKGROUND:Effects of early blood pressure (BP) lowering on cerebral perfusion in patients with moderate/severe occlusive carotid disease after transient ischemic attack (TIA) and non-disabling stroke are uncertain. AIMS:We aimed to evaluate the changes in transcranial Doppler (TCD) indices in patients undergoing blood pressure lowering soon after TIA/non-disabling stroke. METHODS:Consecutive eligible patients (1 November 2011 to 30 October 2018) attending a rapid-access clinic with TIA/non-disabling stroke underwent telemetric home blood pressure monitoring (HBPM) for 1 month and middle cerebral artery velocities measurements ipsilateral to carotid stenosis on TCD ultrasound in the acute setting and at 1 month. Hypertensive patients (HBPM ⩾ 135/85) underwent intensive BP-lowering guided by HBPM unless they had bilateral severe occlusive disease (⩾ 70%). Changes in BP and TCD parameters were compared in patients with extracranial moderate/severe carotid stenosis (between 50% and occlusion) versus those with no or mild (< 50%) stenosis. RESULTS:Of 764 patients with repeated TCD measures, 42 had moderate/severe extracranial carotid stenosis without bilateral severe occlusive disease. HBPM was reduced from baseline to 1 month in hypertensive patients both with versus without moderate/severe carotid stenosis (-12.44/15.99 vs -13.2/12.2 mmHg, respectively, p-difference = 0.82), and changes in TCD velocities (4.69/14.94 vs 2.69/13.86 cm/s, respectively, p-difference = 0.52 for peak systolic velocity and 0.33/7.06 vs 1.75/6.84 cm/s, p-difference = 0.34 for end-diastolic velocity) were also similar, with no evidence of greater hemodynamic compromise in patients with stenosis/occlusion. CONCLUSION:There was no evidence of worsening of TCD hemodynamic indices in patients with moderate/severe occlusive carotid disease treated with BP-lowering soon after TIA/non-disabling stroke, suggesting that antihypertensive treatment in this group of patients is safe in the acute setting of TIA clinics.
10.1177/17474930211068655
Association between blood pressure and different antihypertensive drugs with outcome after ischemic stroke: A Mendelian randomization study.
International journal of stroke : official journal of the International Stroke Society
BACKGROUND:Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke. METHODS:We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month dependence or death defined as a modified Rankin Scale (mRS) of 3-6. The secondary outcome was disability or death after 90 days defined as mRS 2-6. Cochran's Q statistic in the inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-single-nucleotide polymorphism (SNP)-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses. RESULTS:Genetic predisposition to higher systolic and diastolic BP was associated with disability or death after ischemic stroke in univariable IVW MR analysis (odds ratio (OR) 1.29, 95% confidence interval (CI): 1.05-1.59, = 0.014; OR 1.27, 95% CI: 1.07-1.51, = 0.006, respectively). Pulse pressure was associated with both dependence or death and disability or death after ischemic stroke (OR = 1.05, 95% CI: 1.02-1.08, = 0.002; OR = 1.04, 95% CI = 1.01-1.07, = 0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) were significantly associated with improved functional outcomes (dependence or death, OR 0.76, 95% CI: 0.62-0.94, = 0.009; OR 0.89, 95% CI: 0.83-0.97, = 0.005). Proxies for β-blockers, angiotensin receptor blockers (ARB), and thiazides failed to show associations with functional outcomes ( > 0.05). CONCLUSION:We provide evidence for an association of genetic predisposition to higher BP with a higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcomes in ischemic stroke.
10.1177/17474930231185695
Neurological hypertensive emergencies: Correlation of blood pressure values with in-hospital outcomes in ischemic stroke.
European journal of internal medicine
BACKGROUND:Few certainties exist regarding optimal management of Blood Pressure (BP) in the very first hours after an ischemic stroke and many questions remain still unanswered. Our work aimed to evaluate the role of BP and its trend as possible determinants of in-hospital mortality (primary outcome), discharge disabilities and hospitalization length (secondary outcomes) in ischemic stroke patients presented with Hypertensive Emergencies (HE). METHODS:We retrospectively evaluated patients presented to Niguarda Hospital, Emergency Department (ED), from 2015 to 2017 with a neurological ischemic HE. BP at ED presentation (T0), its management in ED (T1) and its values at the stroke unit admission (T2) were evaluated. RESULTS:267 patients were included (0.13 % of all ED accesses and 17.9 % of all ischemic strokes). In the whole population, BP values were not associated with in-hospital mortality while T0 and T2 SBP result were associated to discharge disability and hospitalization length. In pre-specified subgroup analysis these associations were confirmed only in untreated subjects (not anti-hypertensive nor thrombolysis). In fact, no significant relationship can be found between BP values and any secondary outcome in thrombolysis and anti-hypertensive treated patients. CONCLUSIONS:BP values and its management can not be related to in-hospital mortality in stroke patients, presented with HE, while they are associated to discharge disability and hospitalization length. In subgroup analysis, results were confirmed only in untreated (not anti-hypertensive therapies nor thrombolytic).
10.1016/j.ejim.2024.01.029
Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial.
Stroke
BACKGROUND:Acute ischemic stroke (AIS) patients with a history of hypertension experience worse outcomes, which may be explained by a deleterious impact of the renin-angiotensin system (RAS) overactivation. We sought to investigate whether prestroke antihypertensive treatments (AHT) influenced baseline stroke severity and neurological outcomes, in patients with AIS successfully treated by endovascular therapy. METHODS:We performed a post hoc analysis of the BP TARGET trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) and included hypertensive patients with available data regarding AHT at admission, categorized as RAS inhibitors (ACE [angiotensin-converting enzyme] inhibitors, ARBs [angiotensin 2 receptor blockers], and β-blockers) and non-RAS inhibitors (calcium channel blockers and diuretics). Associations of each AHT with National Institutes of Health Stroke Scale (NIHSS) score at baseline were investigated in linear mixed model adjusted for the number of treatments and center. Associations of each AHT with 24-hour NIHSS change, intracranial hemorrhage were performed using linear mixed model adjusted for baseline NIHSS, the number of treatments, center, age, and sex and adjusted for age, sex, diabetes, and current smoking for favorable outcome. All analyses were performed on cases-available data regarding the low number of missing data. RESULTS:Overall, 203 patients with at least one AHT were included. Patients under non-RAS inhibitor treatments had a higher NIHSS score at baseline (adjusted mean difference=3.28 [95% CI, 1.33-5.22]; =0.001). Conversely, patients under RAS inhibitor treatments had a lower baseline NIHSS score (adjusted mean difference=-2.81 [95% CI, -5.37 to -0.25]; =0.031). Intracranial hemorrhage occurrence was significantly more frequent in patients under non-RAS inhibitor treatments (adjusted odds ratio of 2.48 [95% CI, 1.12-5.47]; =0.025). Conversely, the use of RAS inhibitor treatments before AIS was not associated with higher odds of radiographic intracranial hemorrhage. Patients with non-RAS inhibitor treatments had less improvement of NIHSS at 24 hours compared with patients without (adjusted mean difference, 2.83 [95% CI, -0.16 to 5.81]; =0.063). Baseline RAS inhibitor or noninhibitor treatments were not associated with favorable outcome. CONCLUSIONS:We showed an opposite effect of baseline AHT, based on their effect on the RAS. Patients treated with RAS inhibitor agents before AIS exhibited less severe AIS compared with patients under non-RAS inhibitor treatments, developed less intracranial hemorrhage at 24 hours and had a trend toward better NIHSS score at 24 hours. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT03160677.
10.1161/STROKEAHA.121.037548
Clinic and ambulatory blood pressures, blood pressure phenotypes and mortality in patients with a previous stroke.
Hypertension research : official journal of the Japanese Society of Hypertension
There is scarce evidence of the role of clinic and ambulatory BP indices, as well as blood pressure phenotypes in the prognosis of stroke survivors. We aimed to evaluate the association between ambulatory BP indices and mortality in patients with a previous stroke. Our study was an observational cohort study from individuals included in the Spanish Ambulatory Blood Pressure Registry from March 2004 to December 2014. The Cox model was used to estimate associations between usual clinic and ambulatory BP and mortality, adjusted for confounders and additionally for alternative measures of BP. Two thousand one hundred and eighty-three patients with a previous stroke were included. During a median of 9.2 years, 632 (28.9%) patients died: 236 (10.8%) from cardiovascular causes. In the confounder-adjusted model, clinic systolic BP was not associated with the risk of all-cause or cardiovascular mortality. In contrast, systolic BP indices obtained through ABPM (24 h, day and night) were all associated with all-cause and cardiovascular death. In the simultaneous adjustment of daytime and night-time systolic BP, only night-time systolic BP remained significantly associated with all-cause and cardiovascular death: HR 1.35 (95% CI 01.21-1.51) and 1.44 (1.20-1.72), respectively. For diastolic BP, only night-time BP was associated with all-cause and cardiovascular mortality: HR 1.32 (1.18-1.48) and 1.57 (1.31-1.88), respectively. According to the circadian pattern, a riser pattern was associated with all-cause and cardiovascular mortality: HR 1.49 (1.18-1.87) and 1.70 (1.14-2.52), respectively. In conclusion, in patients who have suffered a stroke, night-time BP is the BP estimate most closely associated with all-cause and cardiovascular mortality.
10.1038/s41440-024-01760-1
Blood pressure management for secondary stroke prevention.
Hypertension research : official journal of the Japanese Society of Hypertension
Hypertension is the most important vascular risk factor for stroke; therefore, optimal blood pressure (BP) management is essential for the prevention of recurrent stroke; lowering BP was shown to reduce the risk of recurrent stroke by 25-30%. A recent meta-analysis showed that intensive BP lowering to levels <130/80 mmHg significantly reduced the risk of recurrent stroke compared to standard management with BP levels <140/90 mmHg. The benefit of intensive BP management is evident with regard to a reduced risk of intracranial hemorrhage. Therefore, clinical practice guidelines have established a target BP of <130/80 mmHg. However, the target BP needs to be individualized. A stepped-care approach for cautious BP lowering (usually to levels <140/90 mmHg) is preferred for patients with severe diseases of the major cerebral vessels, who have a high risk of recurrent ischemic stroke. In contrast, more aggressive BP lowering (to levels <120/80 mmHg) tends to benefit patients at high risk of intracranial hemorrhage. The selection of BP management strategies should be guided by the risk of recurrent ischemic and hemorrhagic strokes.
10.1038/s41440-022-00908-1
Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.
The Lancet. Neurology
BACKGROUND:Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS:We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS:Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION:In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING:British Heart Foundation and UK Stroke Association.
10.1016/S1474-4422(19)30197-8
Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.
Lancet (London, England)
BACKGROUND:The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. METHODS:We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. FINDINGS:Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. INTERPRETATION:Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. FUNDING:The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.
10.1016/S0140-6736(22)01882-7
Towards a new classification of atrial fibrillation detected after a stroke or a transient ischaemic attack.
The Lancet. Neurology
Globally, up to 1·5 million individuals with ischaemic stroke or transient ischaemic attack can be newly diagnosed with atrial fibrillation per year. In the past decade, evidence has accumulated supporting the notion that atrial fibrillation first detected after a stroke or transient ischaemic attack differs from atrial fibrillation known before the occurrence of as stroke. Atrial fibrillation detected after stroke is associated with a lower prevalence of risk factors, cardiovascular comorbidities, and atrial cardiomyopathy than atrial fibrillation known before stroke occurrence. These differences might explain why it is associated with a lower risk of recurrence of ischaemic stroke than known atrial fibrillation. Patients with ischaemic stroke or transient ischaemic attack can be classified in three categories: no atrial fibrillation, known atrial fibrillation before stroke occurrence, and atrial fibrillation detected after stroke. This classification could harmonise future research in the field and help to understand the role of prolonged cardiac monitoring for secondary stroke prevention with application of a personalised risk-based approach to the selection of patients for anticoagulation.
10.1016/S1474-4422(23)00326-5
Blood Pressure Management After Endovascular Therapy for Acute Ischemic Stroke: The BEST-II Randomized Clinical Trial.
JAMA
Importance:The effects of moderate systolic blood pressure (SBP) lowering after successful recanalization with endovascular therapy for acute ischemic stroke are uncertain. Objective:To determine the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg). Design, Setting, and Participants:Randomized, open-label, blinded end point, phase 2, futility clinical trial that enrolled 120 patients with acute ischemic stroke who had undergone successful endovascular therapy at 3 US comprehensive stroke centers from January 2020 to March 2022 (final follow-up, June 2022). Intervention:After undergoing endovascular therapy, participants were randomized to 1 of 3 SBP targets: 40 to less than 140 mm Hg, 40 to less than 160 mm Hg, and 40 to 180 mm Hg or less (guideline recommended) group, initiated within 60 minutes of recanalization and maintained for 24 hours. Main Outcomes and Measures:Prespecified multiple primary outcomes for the primary futility analysis were follow-up infarct volume measured at 36 (±12) hours and utility-weighted modified Rankin Scale (mRS) score (range, 0 [worst] to 1 [best]) at 90 (±14) days. Linear regression models were used to test the harm-futility boundaries of a 10-mL increase (slope of 0.5) in the follow-up infarct volume or a 0.10 decrease (slope of -0.005) in the utility-weighted mRS score with each 20-mm Hg SBP target reduction after endovascular therapy (1-sided α = .05). Additional prespecified futility criterion was a less than 25% predicted probability of success for a future 2-group, superiority trial comparing SBP targets of the low- and mid-thresholds with the high-threshold (maximum sample size, 1500 with respect to the utility-weighted mRS score outcome). Results:Among 120 patients randomized (mean [SD] age, 69.6 [14.5] years; 69 females [58%]), 113 (94.2%) completed the trial. The mean follow-up infarct volume was 32.4 mL (95% CI, 18.0 to 46.7 mL) for the less than 140-mm Hg group, 50.7 mL (95% CI, 33.7 to 67.7 mL), for the less than 160-mm Hg group, and 46.4 mL (95% CI, 24.5 to 68.2 mL) for the 180-mm Hg or less group. The mean utility-weighted mRS score was 0.51 (95% CI, 0.38 to 0.63) for the less than 140-mm Hg group, 0.47 (95% CI, 0.35 to 0.60) for the less than 160-mm Hg group, and 0.58 (95% CI, 0.46 to 0.71) for the high-target group. The slope of the follow-up infarct volume for each mm Hg decrease in the SBP target, adjusted for the baseline Alberta Stroke Program Early CT score, was -0.29 (95% CI, -0.81 to ∞; futility P = .99). The slope of the utility-weighted mRS score for each mm Hg decrease in the SBP target after endovascular therapy, adjusted for baseline utility-weighted mRS score, was -0.0019 (95% CI, -∞ to 0.0017; futility P = .93). Comparing the high-target SBP group with the lower-target groups, the predicted probability of success for a future trial was 25% for the less than 140-mm Hg group and 14% for the 160-mm Hg group. Conclusions and Relevance:Among patients with acute ischemic stroke, lower SBP targets less than either 140 mm Hg or 160 mm Hg after successful endovascular therapy did not meet prespecified criteria for futility compared with an SBP target of 180 mm Hg or less. However, the findings suggested a low probability of benefit from lower SBP targets after endovascular therapy if tested in a future larger trial. Trial Registration:ClinicalTrials.gov Identifier: NCT04116112.
10.1001/jama.2023.14330
Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke.
The New England journal of medicine
BACKGROUND:Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied. METHODS:In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days. RESULTS:A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03). CONCLUSIONS:Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).
10.1056/NEJMoa2309137
Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials.
Lancet (London, England)
BACKGROUND:Inflammation and hyperlipidaemia jointly contribute to atherothrombotic disease. However, when people are treated with intensive statin therapy, the relative contributions of inflammation and hyperlipidaemia to the risk of future cardiovascular events might change, which has implications for the choice of adjunctive cardiovascular therapeutics. We aimed to evaluate the relative importance of high-sensitivity C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDLC) as determinants of risk for major adverse cardiovascular events, cardiovascular death, and all-cause-death among patients receiving statins. METHODS:We did a collaborative analysis of patients with-or at high risk of-atherosclerotic disease, who were receiving contemporary statins and were participants in the multinational PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials. Quartiles of increasing baseline high-sensitivity CRP (a biomarker of residual inflammatory risk) and of increasing baseline LDLC (a biomarker of residual cholesterol risk) were assessed as predictors of future major adverse cardiovascular events, cardiovascular death, and all-cause death. Hazard ratios (HRs) for cardiovascular events and deaths were calculated across quartiles of high-sensitivity CRP and LDLC in analyses adjusted for age, gender, BMI, smoking status, blood pressure, previous history of cardiovascular disease, and randomised treatment group assignment. FINDINGS:31 245 patients were included in the analysis from the PROMINENT (n=9988), REDUCE-IT (n=8179), and STRENGTH (n=13 078) trials. The observed ranges for baseline high-sensitivity CRP and LDLC, and the relationships of each biomarker to subsequent cardiovascular event rates, were almost identical in the three trials. Residual inflammatory risk was significantly associated with incident major adverse cardiovascular events (highest high-sensitivity CRP quartile vs lowest high-sensitivity CRP quartile, adjusted HR 1·31, 95% CI 1·20-1·43; p<0·0001), cardiovascular mortality (2·68, 2·22-3·23; p<0·0001), and all-cause mortality (2·42, 2·12-2·77; p<0·0001). By contrast, the relationship of residual cholesterol risk was neutral for major adverse cardiovascular events (highest LDLC quartile vs lowest LDLC quartile, adjusted HR 1·07, 95% CI 0·98-1·17; p=0·11), and of low magnitude for cardiovascular death (1·27, 1·07-1·50; p=0·0086) and all-cause death (1·16, 1·03-1·32; p=0·025). INTERPRETATION:Among patients receiving contemporary statins, inflammation assessed by high-sensitivity CRP was a stronger predictor for risk of future cardiovascular events and death than cholesterol assessed by LDLC. These data have implications for the selection of adjunctive treatments beyond statin therapy and suggest that combined use of aggressive lipid-lowering and inflammation-inhibiting therapies might be needed to further reduce atherosclerotic risk. FUNDING:Kowa Research Institute, Amarin, AstraZeneca.
10.1016/S0140-6736(23)00215-5
Triglycerides and Residual Atherosclerotic Risk.
Raposeiras-Roubin Sergio,Rosselló Xavier,Oliva Belén,Fernández-Friera Leticia,Mendiguren José M,Andrés Vicente,Bueno Héctor,Sanz Javier,Martínez de Vega Vicente,Abu-Assi Emad,Iñiguez Andrés,Fernández-Ortiz Antonio,Ibáñez Borja,Fuster Valentin
Journal of the American College of Cardiology
BACKGROUND:Even when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C. OBJECTIVES:This study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals. METHODS:An observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography. RESULTS:Atherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003). CONCLUSIONS:In individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).
10.1016/j.jacc.2021.04.059
Atherosclerotic plaque characteristics in extracranial carotid artery may indicate closer association with white matter hyperintensities than intracranial arteries: A CARE-II study.
European journal of radiology
PURPOSE:This study aimed to investigate the associations of atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries with severity of white matter hyperintensities (WMHs) in symptomatic patients using magnetic resonance (MR) imaging. METHOD:Patients with cerebrovascular symptoms and carotid plaque were recruited from the cross-sectional, multicenter study of CARE-II. Luminal stenosis of intracranial and extracranial carotid arteries, carotid plaque compositional features, and WMHs were evaluated by brain structural and vascular MR imaging. The atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries were compared between patients with and without moderate-to-severe WMHs (Fazekas score > 2), and their associations with severity of WMHs were analyzed using logistic regression. RESULTS:Of the recruited 622 patients (mean age, 58.7 ± 10.9 years; 422 males), 221 (35.5 %) had moderate-to-severe WMHs with higher prevalence of moderate-to-severe luminal stenosis (17.0 % vs. 10.4 %), intraplaque hemorrhage (15.7 % vs. 9.0 %), thin/ruptured fibrous cap (30.2 % vs. 20.4 %), calcification (44.4 % vs. 22.2 %) and lipid-rich necrotic core (63.8 % vs. 51.1 %) in carotid artery compared to those without (all P < 0.05). Multivariate logistic regression showed that carotid calcification (OR, 1.854; 95 % CI, 1.187-2.898; P = 0.007) was independently associated with moderate-to-severe WMHs after adjusting for confounding factors. No significant association was found between intracranial atherosclerotic stenosis and moderate-to-severe WMHs (P > 0.05). CONCLUSION:Carotid atherosclerotic plaque features, particularly presence of calcification, were independently associated with severity of WMHs, but such association was not found in intracranial atherosclerotic stenosis, suggesting that carotid atherosclerotic plaque characteristics may have closer association with severity of WMHs compared to intracranial atherosclerosis.
10.1016/j.ejrad.2023.111208
Relations of lipid parameters, other variables with carotid intima-media thickness and plaque in the general Chinese adults: an observational study.
Hou Qingtao,Li Sheyu,Gao Yun,Tian Haoming
Lipids in health and disease
BACKGROUND:It has been reported that non-high-density lipoprotein cholesterol (non-HDL-C) and lipid ratios, including total cholesterol (TC) / high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) / HDL-C, are better predictors for atherosclerosis than conventional lipid profiles. However, there have been few studies comparing the predictive values of different lipid parameters for early atherosclerosis. The aim of this study was to determine the relevant factors of carotid intima-media thickness (IMT) and plaque in the general Chinese adults and analyze the predictive values of different lipid parameters for carotid IMT and plaque. METHODS:We collected the demographics, anthropometrics, and laboratory data of 311 Chinese adults without the diagnoses of acute myocardial infarction, stroke, heart failure, peripheral arterial disease, end-stage renal disease or malignant tumor. The carotid IMT and the presence of carotid plaque were evaluated by high-resolution color Doppler ultrasonography. RESULTS:Based on the cutoff level of 0.9 mm, the percentage of people with a thickened IMT was 8.4%. And the percentage of people with carotid plaque was 15.8%. Among the lipid parameters, the levels of TC, non-HDL-C and LDL-C were more closely related to carotid IMT and plaque compared with other lipid parameters in the univariate analyses. In multivariate analyses, age, gender and systolic blood pressure (SBP) remained significantly with carotid IMT, whereas age, gender, diastolic blood pressure (DBP) and the TC level remained significantly with carotid plaque. Non-HDL-C level remained significantly with carotid plaque after adjusting for age, gender, waist-hip ratio (WHR), smoking, drinking, SBP and fasting plasma glucose (FPG). CONCLUSIONS:Age, gender, SBP are important predictors for carotid IMT. Age, gender, DBP and TC are important predictors for carotid plaque. TC, LDL-C and non-HDL-C have greater predictive values for IMT and the presence of carotid plaque compared with other lipid parameters, among which TC has the greatest predictive value for the presence of carotid plaque. The predictive value of non-HDL-C for carotid IMT and plaque is not inferior to that of LDL-C.
10.1186/s12944-018-0758-9
Association of brachial-ankle pulse wave velocity and carotid plaque in Chinese hypertensive adults: effect modification by age.
Liu Zhihao,Yang Ying,Zhang Yan,Xie Liling,Li Qinqin,Song Yun,Liu Lishun,Liu Chengzhang,Xu Benjamin,Wang Binyan,Yi Tieci,Fan Fangfang,Ma Wei,Weng Haoyu,Zhang Nan,Xu Xiping,Wang Xiaobin,Qin Xianhui,Huo Yong,Li Jianping
Hypertension research : official journal of the Japanese Society of Hypertension
We aimed to investigate the association of brachial-ankle pulse wave velocity (baPWV) with carotid plaque presence and carotid plaque number in a Chinese hypertensive population. A total of 13,554 hypertensive subjects from the China Stroke Primary Prevention Trial (CSPPT) were recruited. Arterial stiffness and carotid plaque were evaluated by baPWV and B-mode ultrasonography, respectively. Multivariate logistic regression analysis was used to determine the correlation of baPWV and carotid plaque presence. Multinomial logistic regression analysis was used to determine the correlation of baPWV and carotid plaque number. Further interactions between baPWV and carotid plaque presence were examined using subgroup analysis. Continuous baPWV was positively correlated with carotid plaque presence (OR = 1.05, 95% CI: 1.04-1.07) and carotid plaque number (one- to two-plaque group: OR = 1.04, 95% CI: 1.02-1.06; three-or-more-plaque group: OR = 1.09, 95% CI: 1.07-1.12). When baPWV was classified into quartiles, with the lowest quartile as reference, the ORs for having one, two, or three or more plaques increased in parallel with the quartiles of baPWV, indicating a dose-dependent effect. In a subgroup analysis, the association of baPWV and carotid plaque presence was more pronounced among younger participants (OR: 1.14 vs. 1.06 and 1.03 for the age groups <60 years, 60 ≤ 70 years, and ≥70 years, respectively, P for interaction <0.001). In a Chinese hypertensive population, baPWV was positively associated with carotid plaque presence and carotid plaque number. A more pronounced positive association between baPWV and carotid plaque presence was observed in younger participants.
10.1038/s41440-020-0432-2
Differential associations of systolic and diastolic time rate of blood pressure variation with carotid atherosclerosis and plaque echogenicity.
Kolyviras Athanasios,Manios Efstathios,Georgiopoulos Georgios,Michas Fotios,Gustavsson Thomas,Papadopoulou Efthimia,Ageliki Laina,Kanakakis John,Papamichael Christos,Stergiou Georgios,Zakopoulos Nikolaos,Stamatelopoulos Kimon
Journal of clinical hypertension (Greenwich, Conn.)
In the current study, the authors sought to assess whether the time rate of systolic and diastolic blood pressure variation is associated with advanced subclinical stages of carotid atherosclerosis and plaque echogenicity assessed by gray scale median. The authors recruited 237 consecutive patients with normotension and hypertension who underwent 24-hour ambulatory blood pressure monitoring and carotid artery ultrasonography. There was an independent association between low 24-hour systolic time rate and increased echogenicity of carotid plaques (adjusted odds ratio for highest vs lower tertiles of gray scale median, 0.470; 95% confidence interval, 0.245-0.902 [P = .023]). Moreover, increased nighttime diastolic time rate independently correlated with the presence (adjusted odds ratio, 1.328; P = .015) and number of carotid plaques (adjusted odds ratio, 1.410; P = .003). These results indicate differential associations of the systolic and diastolic components of time rate of blood pressure variation with the presence, extent, and composition of carotid plaques and suggest that when blood pressure variation is assessed, both components should be considered.
10.1111/jch.13070
Combined effects of carotid plaques and hypertension on the risk of cardiovascular disease and all-cause mortality.
Li Wen,Zhao Jianqiu,Song Lu,Chen Shuohua,Liu Xuemei,Wu Shouling
Clinical cardiology
BACKGROUND:Both hypertension and atherosclerotic plaques are risk factors for cardiovascular disease (CVD). HYPOTHESIS:This study aimed to investigate whether the combined effects of carotid plaques and hypertension increase the risks of CVD and all-cause mortality. METHODS:Patients from the stroke and elderly cohorts of the Kailuan study in China who completed a carotid sonography examination were included in the study. Participants in both cohorts underwent physical examinations between 2010 and 2011 and were divided into four groups: no carotid plaques with normal blood pressure (n = 2227), hypertension only (n = 1290), carotid plaques only (n = 1128), and hypertension with carotid plaques (n = 1862). The outcomes included the first occurrence of CVD and all-cause mortality. RESULTS:Among the 6507 participants (mean age, 58.1 ± 11.8 years, 61% males), 157 cardiovascular events, and 210 deaths occurred after average follow-ups of 4.5 and 4.9 years, respectively. After adjusting for covariates, carotid plaques only and hypertension with carotid plaques were associated with excess risk (hazard ratio [HR]; confidence interval [CI]) for the first occurrence of CVD (HR = 1.85; 95% CI, 1.01-3.44; and HR = 2.97; 95% CI, 1.66-5.29, respectively), cerebral infarction (HR = 2.66; 95% CI, 1.16-6.15; and HR = 4.15; 95% CI, 1.87-9.19, respectively), and all-cause mortality (HR = 1.96; 95% CI, 1.16-3.31; and HR = 1.85; 95% CI, 1.09-3.13, respectively). CONCLUSIONS:The combination of hypertension and atherosclerotic plaques may increase the risk of CVD events and all-cause mortality, especially cerebral infarction, compared with participants without those factors.
10.1002/clc.23372
Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression.
Ganji Morsaleh,Nardi Valentina,Prasad Megha,Jordan Kyra L,Bois Melanie C,Franchi Federico,Zhu Xiang Y,Tang Hui,Young Melissa D,Lerman Lilach O,Lerman Amir
Stroke
Background and Purpose:XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors. Methods:Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured. Results:Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median [interquartile range]: 1.24 [2.09] versus 0.16 [0.34]; P<0.001) and with significantly higher circulating uric acid levels (mean±SD: 7.36±2.10 versus 5.37±1.79 mg/dL; P<0.001, respectively). In addition, XO expression in atherosclerotic carotid plaque was inversely associated with serum high-density lipoproteins cholesterol levels (P=0.010, r=−0.30) and directly with circulating uric acid levels (P<0.001, r=0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median [interquartile range]: 93.37% [25] versus 46.15% [21], respectively; P<0.001). Conclusions:XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.
10.1161/STROKEAHA.120.032964
Comparison of carotid atherosclerotic plaque characteristics between symptomatic patients with transient ischemic attack and stroke using high-resolution magnetic resonance imaging.
BMC cardiovascular disorders
BACKGROUND:This study aimed to compare the characteristics of carotid plaques between patients with transient ischemic attack (TIA) and ischemic stroke using magnetic resonance (MR) imaging. METHODS:Patients with a recent ischemic stroke or TIA who exhibited atherosclerotic plaques of carotid arteries in the symptomatic sides determined by MR vessel wall imaging were recruited. The plaque morphology and compositions including intraplaque hemorrhage (IPH), lipid-rich necrotic-core (LRNC) and calcification were compared between TIA and stroke patients. Logistic regression was performed to relate the plaque characteristics to the types of ischemic events. RESULTS:A total of 270 patients with TIA or ischemic stroke were recruited. Stroke patients had a significantly higher prevalence of diabetes (42.2% vs. 28.2%, p = 0.021), greater mean wall area (35.1 ± 10.1 mm vs. 32.0 ± 7.7 mm, p = 0.004), mean wall thickness (1.3 ± 0.2 mm vs. 1.2 ± 0.2 mm, p = 0.001), maximum normalized wall index (NWI)(63.9% ± 6.0% vs. 62.2% ± 5.9%, p = 0.023) and %volume of LRNC (9.7% ± 8.2% vs. 7.4% ± 7.9%, p = 0.025) in the carotid arteries compared to those with TIA. After adjustment for clinical factors, above characteristics of carotid arteries were significantly associated with the type of ischemic events. After further adjustment for maximum NWI, this association remained statistically significant (OR, 1.41; CI, 1.01-1.96; p = 0.041). CONCLUSIONS:Ischemic stroke patients had larger plaque burden and greater proportion of LRNC in carotid plaques compared to those with TIA. This study suggests that ischemic stroke patients had more vulnerable plaques compared to those with TIA.
10.1186/s12872-022-02624-7
Association between Metabolic Syndrome and Carotid Atherosclerosis: A Cross-sectional Study in Northern China.
Zhou Ping An,Zhang Chen Huan,Chen Yan Ru,Li Dong,Song Dai Yu,Liu Hua Min,Zhou Ming Yue,Song Guo Shun,Chen Sheng Yun
Biomedical and environmental sciences : BES
OBJECTIVE:Increased carotid artery intima-media thickness (CIMT) and carotid plaque as manifestations of carotid atherosclerosis have been used as markers of cardiovascular disease (CVD). The components of metabolic syndrome (MetS) are linked to CVD, but the association between MetS and CVD is controversial. METHODS:A total of 8,933 Chinese adults aged 40 years or older from 2010 to 2014 were selected from the Jidong and Kailuan communities. MetS was defined by the International Diabetes Federation criteria. CIMT and carotid plaque were measured using color Doppler ultrasound. Logistic regression models were used to assess the association of MetS with carotid plaque and CIMT. RESULTS:MetS was found among 3,461 (3,461/8,933) participants. The odds ratio and 95% confidence internal (CI) for carotid plaques in participants with MetS was 1.16 (1.03-1.30). The risk of carotid plaques increased with the number of MetS components. The average CIMT was higher in participants with MetS (β = 0.020, 95% CI, 0.014-0.027) and in participants with more MetS components. CONCLUSION:Individuals with MetS are at an increased risk for carotid atherosclerosis compared to those without MetS.
10.3967/bes2019.114
Circulatory markers of immunity and carotid atherosclerotic plaque.
Fani Lana,van Dam-Nolen Dianne H K,Vernooij Meike,Kavousi Maryam,van der Lugt Aad,Bos Daniel
Atherosclerosis
BACKGROUND AND AIMS:We aimed to determine the association of circulatory markers of innate and adaptive immunity with carotid atherosclerotic plaque characteristics. METHODS:In 1602 participants from the population-based Rotterdam Study with subclinicalcarotid atherosclerosis, blood sampling was performed to determine granulocyte, platelet, monocyte (innate immunity) and lymphocyte (adaptive immunity) counts, from which the granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], monocyte-to-lymphocyte ratio [MLR] and systemic immune-inflammation index [SII] were calculated. All participants underwent carotid MRI for evaluation of plaque characteristics. Plaque size (stenosis >30%, maximum plaque thickness) and plaque composition (presence of intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], and calcification) were assessed. Using linear and logistic regression models, the association of innate and adaptive immunity markers with plaque size and plaque components, adjusting for relevant confounders, was assessed. RESULTS:Higher levels of granulocytes were significantly associated with larger plaque thickness (mean difference [Ln (mm)] per Ln increase granulocyte count [95% CI]: 0.06 [0.02; 0.10]). Conversely, more lymphocytes related with smaller maximum plaque thickness (mean difference [Ln (mm)] per Ln increase lymphocyte count: 0.09 [-0.14;-0.04]) and a lower prevalence of IPH (odds ratio per Ln increase lymphocyte count: 0.60 [0.37; 0.97]). Moreover, all ratio measures were associated with larger plaque thickness, of which the MLR also associated with more frequent LRNC (odds ratio per Ln increase MLR: 1.26 [1.02; 1.56]). CONCLUSIONS:The innate immunity links to larger plaques, whilst the adaptive immunity seems to relate to smaller plaques and a lower frequency of IPH. These results suggest that an imbalance in innate and adaptive immunity may play a role in the vulnerability of carotid atherosclerotic plaques.
10.1016/j.atherosclerosis.2021.03.040
Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis.
van Dam-Nolen Dianne H K,van Egmond Nina C M,Dilba Kristine,Nies Kelly,van der Kolk Anja G,Liem Madieke I,Kooi M Eline,Hendrikse Jeroen,Nederkoorn Paul J,Koudstaal Peter J,van der Lugt Aad,Bos Daniel
Stroke
BACKGROUND AND PURPOSE:Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes. METHODS:We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and <70% ipsilateral carotid stenosis. Plaque characteristics (intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], calcifications, thin-or-ruptured fibrous cap, ulcerations, total plaque volume) were assessed with magnetic resonance imaging and multidetector-row computed tomography angiography. We used multivariable logistic and linear regression analyses to assess sex differences in plaque characteristics. RESULTS:We found significant difference in total plaque volume between men and women (β=22.9 mm [95% CI, 15.4-30.5]; mean volume in men 1399±425 mm, in women 1011±242 mm). Additionally, men were more likely to have IPH (odds ratio [OR]=2.8 [95% CI, 1.3-6.3]; IPH proportion in men 49%, in women 16%) and LRNC (OR=2.4 [95% CI, 1.2-4.7]; LRNC proportion in men 73%, in women 41%) even after adjustment for total plaque volume. We found no sex-specific differences in plaque volume-corrected volumes of IPH, LRNC, and calcifications. In terms of coexistence of plaque characteristics, we found that men had more often a plaque with coexistence of calcifications, LRNC, and IPH (OR=2.7 [95% CI, 1.2-7.0]), with coexistence of thin-or-ruptured fibrous cap/ulcerations, LRNC, and IPH (OR=2.4 [95% CI, 1.1-5.9]), and with coexistence of all plaque characteristics (OR=3.0 [95% CI, 1.2-8.6]). CONCLUSIONS:In symptomatic patients with mild-to-moderate carotid stenosis, men are more likely to have a high-risk carotid plaque with IPH and LRNC than women, regardless of total plaque burden. Men also have more often a plaque with multiple vulnerable plaque components, which could comprise an even higher stroke risk. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01208025.
10.1161/STROKEAHA.121.036564
Carotid vulnerable plaque coexisting with cerebral small vessel disease and acute ischemic stroke: a Chinese Atherosclerosis Risk Evaluation study.
European radiology
OBJECTIVES:We aimed to investigate the associations between carotid vulnerable plaque features coexisting with cerebral small vessel diseases (CSVDs) and acute ischemic stroke (AIS) and, furthermore, to determine whether coexisting diseases had a stronger association with AIS than a single disease. METHODS:Patients with cerebrovascular symptoms and carotid plaque were recruited from the cross-sectional, multicenter CARE-II study. The population was divided into two groups (AIS and transient ischemic stroke (TIA)). MRI features of carotid plaques (including luminal stenosis and plaque vulnerabilities) and CSVDs (such as white matter hyperintensities (WMHs) and lacunes) were evaluated. Coexisting diseases were defined as the presence of at least one carotid plaque features and one or more CSVDs feature. Multivariate logistic regression was performed to examine the associations between coexisting diseases and AIS. RESULTS:Of the recruited 634 patients (mean age: 59.1 ± 11.3 years; 429 males), 312 (49.2%) patients had AIS. These subjects had a higher prevalence of carotid vulnerable plaques, lacunes, and moderate-to-severe WMHs (a total Fazekas score of 3-6) than those with TIA (42.6% vs. 29.5%, 59.6% vs. 26.4%, 69.9% vs. 60.6%, respectively, all p < 0.05). Multivariate analysis revealed that carotid plaque features coexisting with lacunes or moderate-to-severe WMHs had a stronger association with AIS compared to carotid lesions alone (all p < 0.05) (i.e., vulnerable plaque coexisting with lacunes vs. vulnerable plaque alone, adjusted odds ratio: 3.67 vs. 1.62). CONCLUSIONS:Carotid vulnerable plaque features coexisting with CSVDs, particularly lacunes, had a stronger association with AIS compared to carotid lesions alone in a large, symptomatic, cohort. TRIAL REGISTRATION:Clinical trial registration URL: http://www. CLINICALTRIALS:gov , unique identifier: NCT02017756 KEY POINTS: • Carotid vulnerable plaque features coexisting with cerebral small vessel diseases, such as lacunes, had a stronger association with acute ischemic stroke compared to single diseases in symptomatic patients. • A comprehensive assessment of coexisting cerebrovascular diseases may help stratify the risk of acute ischemic stroke.
10.1007/s00330-022-08757-9
Carotid Plaque Characteristics Predict Recurrent Ischemic Stroke and TIA: The PARISK (Plaque At RISK) Study.
JACC. Cardiovascular imaging
BACKGROUND:Patients with symptomatic carotid stenosis are at high risk for recurrent stroke. The decision for carotid endarterectomy currently mainly relies on degree of stenosis (cutoff value >50% or 70%). Nevertheless, also, patients with mild-to-moderate stenosis still have a considerable recurrent stroke risk. Increasing evidence suggests that carotid plaque composition rather than degree of stenosis determines plaque vulnerability; however, it remains unclear whether this also provides additional information to improve clinical decision making. OBJECTIVES:The PARISK (Plaque At RISK) study aimed to improve the identification of patients at increased risk of recurrent ischemic stroke using multimodality carotid imaging. METHODS:The authors included 244 patients (71% men; mean age, 68 years) with a recent symptomatic mild-to-moderate carotid stenosis in a prospective multicenter cohort study. Magnetic resonance imaging (carotid and brain) and computed tomography angiography (carotid) were performed at baseline and after 2 years. The clinical endpoint was a recurrent ipsilateral ischemic stroke or transient ischemic attack (TIA). Cox proportional hazards models were used to assess whether intraplaque hemorrhage (IPH), ulceration, proportion of calcifications, and total plaque volume in ipsilateral carotid plaques were associated with the endpoint. Next, the authors investigated the predictive performance of these imaging biomarkers by adding these markers (separately and simultaneously) to the ECST (European Carotid Surgery Trial) risk score. RESULTS:During 5.1 years follow-up, 37 patients reached the clinical endpoint. IPH presence and total plaque volume were associated with recurrent ipsilateral ischemic stroke or TIA (HR: 2.12 [95% CI: 1.02-4.44] for IPH; HR: 1.07 [95% CI: 1.00-1.15] for total plaque volume per 100 µL increase). Ulcerations and proportion of calcifications were not statistically significant determinants. Addition of IPH and total plaque volume to the ECST risk score improved the model performance (C-statistics increased from 0.67 to 0.75-0.78). CONCLUSIONS:IPH and total plaque volume are independent risk factors for recurrent ipsilateral ischemic stroke or TIA in patients with mild-to-moderate carotid stenosis. These plaque characteristics improve current decision making. Validation studies to implement plaque characteristics in clinical scoring tools are needed. (PARISK: Validation of Imaging Techniques [PARISK]; NCT01208025).
10.1016/j.jcmg.2022.04.003
Carotid Plaque Vulnerability Assessed by Contrast-Enhanced Ultrasound and Clinical Risk Factors.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
AIM:To evaluate the vulnerability of carotid plaque by contrast-enhanced ultrasound, to study the clinical risk factors of the plaque, and to analyze the relationship between plaque vulnerability and clinical indicators. MATERIALS AND METHODS:244 patients with carotid plaque were selected for contrast-enhanced ultrasound examination, biochemical and other indicators were detected, and the stability of plaque was evaluated by semi-quantitative visual grading of intraplaque neovascularization (IPN), and correlation between plaque and each indicator was analyzed. RESULTS:Different grades of neovascularization in plaque had statistical differences with BMI, arm circumference, WHR, WBC, CRP, tHcy, TBIL, DBIL, SUA, LP (a) and DD (P<0.05). Correlation analysis showed that TBIL, DBIL were negatively correlated with the grading, while others were positively correlated. CONCLUSION:The expression levels of SUA, tHcy, TC, TG, LDL-C, LP (a), DD, WBC and CRP are closely related to contrast-enhanced ultrasound grading, which further indicated the vulnerability of plaque and provides theoretical basis for clinical treatment.
10.1016/j.jstrokecerebrovasdis.2022.106598
Non-traditional lipid parameters as potential predictors of carotid plaque vulnerability and stenosis in patients with acute ischemic stroke.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
OBJECTIVE:Lipid abnormalities are important risk factors in patients with large atherosclerotic strokes. Recent studies have shown that non-traditional lipid parameters are crucial to the development of atherosclerosis and are closely related to the clinical outcome of acute ischemic stroke (AIS). Therefore, we aimed to investigate the relationship between non-traditional lipid parameters and carotid plaque stability and stenosis degree in patients with large atherosclerotic stroke. METHODS:We retrospectively analyzed 336 patients with AIS. All patients were divided into the non-plaque group, stable plaque group, and vulnerable plaque group according to ultrasound examination. At the same time, the patients were divided into non-stenosis, mild stenosis, moderate stenosis, and severe stenosis groups according to the degree of stenosis. Non-traditional lipid parameters, including residual lipoprotein cholesterol (RLP-C), non-high-density lipoprotein cholesterol (non-HDL-C), non-HDL-C to high-density lipoprotein cholesterol ratio (non-HDL-C/HDL-C), triglyceride to HDL-C ratio (TG/HDL-C), Castelli's risk index (CRI), and the atherogenic index of plasma (AIP). Receiver operating characteristic (ROC) curves and multivariate logistic regression analyses were used to investigate the associations between the non-traditional lipid parameters and carotid plaque vulnerability. Spearman linear correlation analysis was used to test the correlation between variables and the degree of carotid plaque stenosis. RESULTS:This study population included 336 patients with AIS, of whom 294 had a carotid plaque. Multivariate logistic regression model showed that RLP-C (OR, 3.361; 95%CI, 1.311-8.617), non-HDL-C/HDL-C (OR, 1.699; 95%CI, 1.279-2.258), non-HDL-C (OR, 1.704; 95%CI, 1.143-2.540), CRI-I (OR, 1.573; 95%CI, 1.196-2.068), and CRI-II (OR, 2.022; 95%CI, 1.369-2.985) were independent risk factors for carotid plaque vulnerability. In addition, Spearman correlation analysis showed that the values of RLP-C, non-HDL-C/HDL-C, non-HDL-C, TG/HDL-C, CRI-I, CRI-II, and AIP on admission were positively correlated with the degree of carotid plaque stenosis (all P < 0.001). CONCLUSION:This study provides evidence that non-traditional lipid parameters (LP-C, non-HDL-C/HDL-C, non-HDL-C, CRI-I, and CRI-II) were potential predictors of carotid plaque vulnerability in patients with AIS. However, no significant correlation was observed between TG/HDL-C and AIP. RLP-C, non-HDL-C/HDL-C, non-HDL-C, TG/HDL-C, CRI-I, CRI-II, and AIP were closely related to the degree of carotid plaque stenosis. Non-traditional lipid parameters can be used as novel biomarkers of carotid plaque vulnerability and stenosis.
10.1007/s10072-022-06472-3
The human carotid atherosclerotic plaque: an observational review of histological scoring systems.
European review for medical and pharmacological sciences
OBJECTIVE:The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed. SUBJECTS AND METHODS:Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques. RESULTS:A thin fibrous cap (<65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture. CONCLUSIONS:Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events.
10.26355/eurrev_202304_32179
Physiological Bases for the Superiority of Apolipoprotein B Over Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol as a Marker of Cardiovascular Risk.
Journal of the American Heart Association
In 2019, the European Society of Cardiology/European Atherosclerosis Society stated that apolipoprotein B (apoB) was a more accurate marker of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol. Since then, the evidence has continued to mount in favor of apoB. This review explicates the physiological mechanisms responsible for the superiority of apoB as a marker of the cardiovascular risk attributable to the atherogenic apoB lipoprotein particles chylomicron remnants, very low-density lipoprotein, and low-density lipoprotein particles. First, the nature and relative numbers of these different apoB particles will be outlined. This will make clear why low-density lipoprotein particles are almost always the major determinants of cardiovascular risk and why the concentrations of triglycerides and LDL-C may obscure this relation. Next, the mechanisms that govern the number of very low-density lipoprotein and low-density lipoprotein particles will be outlined because, except for dysbetalipoproteinemia, the total number of apoB particles determines cardiovascular risk, Then, the mechanisms that govern the cholesterol mass within very low-density lipoprotein and low-density lipoprotein particles will be reviewed because these are responsible for the discordance between the mass of cholesterol within apoB particles, measured either as LDL-C or non-high-density lipoprotein cholesterol, and the number of apoB particles measured as apoB, which creates the superior predictive power of apoB over LDL-C and non-high-density lipoprotein cholesterol. Finally, the major apoB dyslipoproteinemias will be briefly outlined. Our objective is to provide a physiological framework for health care givers to understand why apoB is a more accurate marker of cardiovascular risk than LDL-C or non-high-density lipoprotein cholesterol.
10.1161/JAHA.122.025858
Serum C-reactive protein to albumin ratio as a reliable marker of diabetic neuropathy in type 2 diabetes mellitus.
Biomolecules & biomedicine
In various diseases characterized by inflammation, the C-reactive protein to albumin ratio (CAR) serves as a marker of inflammation. Type 2 diabetes mellitus (T2DM) is frequently complicated by diabetic neuropathy (DN) and timely diagnosis is crucial for treatment and potential reversal of this complication. Since both DN and T2DM are associated with chronic, low-grade inflammation, our study aimed to evaluate CAR levels in type 2 diabetic subjects with DN and compare them to those in subjects without DN. Patients presenting to our institutional outpatient clinics were divided into two groups based on the presence of DN. Data on characteristics and laboratory measures, including CAR,were compared between the DN and non-DN groups. The median CAR in the DN and non-DN groups was 2.19% (range 0.2%-49%) and 0.56% (range 0.02%-5.8%), respectively (P < 0.001). CAR showed significant positive correlations with weight (r = 0.19, P = 0.01), body mass index (BMI) (r = 0.11, P = 0.03), waist circumference (r = 0.10, P = 0.046), fasting glucose (r = 0.14, P = 0.004), serum creatinine (r = 0.25, P < 0.001), triglyceride (r = 0.17, P < 0.001), and LDL-cholesterol (r = 0.13, P = 0.001) levels, and an inverse correlation with estimated glomerular filtration rate (eGFR) (r = -0.16, P < 0.001). Additionally, CAR demonstrated a sensitivity of 78% and specificity of 73% for predicting DN at a threshold of 1.02% (area under curve [AUC] 0.84, 95% confidence interval [CI] 0.82-0.87, P < 0.001). High CAR levels were independently associated with an increased risk of DN (odds ratio [OR] 1.34, 95% CI 1.08-1.62, P < 0.001). Elevated CAR levels may thus be considered a potential marker for DN in T2DM patients.
10.17305/bb.2024.10426
Arterial stiffness and carotid intima-media thickness in diabetic peripheral neuropathy.
Avci Ahmet,Demir Kenan,Kaya Zeynettin,Marakoglu Kamile,Ceylan Esra,Ekmekci Ahmet Hakan,Yilmaz Ahmet,Demir Aysegul,Altunkeser Bulent Behlul
Medical science monitor : international medical journal of experimental and clinical research
BACKGROUND:We investigated the relationship between peripheral neuropathy and parameters of arterial stiffness and carotid intima media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS:The study included 161 patients (80 females and 81 males), 69 of whom had peripheral neuropathy. All patients underwent 24-h blood pressure monitoring, and arterial stiffness parameters were measured. The CIMT was measured using B-mode ultrasonography and patients also underwent transthoracic echocardiographic examination. RESULTS:Patients with peripheral neuropathy, compared with those without it, were older (54.68±8.35 years vs. 51.04±7.89 years; p=0.005) and had T2DM for longer periods (60 vs. 36 months; p=0.004). Glycated hemoglobin (HbA1c) values (8.55±1.85 mg/dL vs. 7.30±1.51 mg/dL; p<0.001), pulse wave velocity (PWV) (7.74±1.14 m/s vs. 7.15±1.10 m/s; p=0.001), CIMT (anterior 0.74±0.15 mm vs. 0.67±0.13 mm; p=0.01), and left ventricular mass (LVM) index (98.68±26.28 g/m2 vs. 89.71±19.70 g/m2; p=0.02) were all significantly increased in the group with peripheral neuropathy compared to the group without peripheral neuropathy. We determined that duration of diabetes, HbA1c, and LVM index were predictors of peripheral neuropathy. CONCLUSIONS:A significant relationship was found between diabetic neuropathy and increased PWV, a parameter of arterial stiffness, as well as CIMT, a marker of systemic atherosclerosis. Diabetic peripheral neuropathy may be a determinant of subclinical atherosclerosis in T2DM.
10.12659/MSM.892648
The Association between the Severity of Distal Sensorimotor Polyneuropathy and Increased Carotid Atherosclerosis in Individuals with Type 2 Diabetes.
Diagnostics (Basel, Switzerland)
BACKGROUND:Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM) Method: Participants underwent comprehensive assessments including nerve conduction studies (NCS), Toronto Clinical Neuropathy Score (TCNS) evaluations, assessment of cardiometabolic risk factors, and carotid sonography studies covering dynamic and morphological parameters. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) in both the common carotid artery (CCA) and internal carotid artery (ICA), carotid intima-media thickness (IMT), and carotid plaque score (CPS) were also measured. Peripheral nerve function severity was assessed using composite amplitude scores (CAS) derived from NCS. RESULTS:Individuals with DSPN exhibited lower EDV in the CCA and ICA ( < 0.0001 and = 0.002), higher PI and RI in both CCA and ICA (all < 0.0001), and higher CPS ( = 0.002). They also demonstrated a higher prevalence of retinopathy as an underlying condition, higher index HbA1c, and reduced estimated glomerular filtration rate (eGFR) (all < 0.0001). Multiple linear regression analysis revealed significant associations where eGFR, ICA-PI, index HbA1c, waist circumference, and age were correlated with CAS. Meanwhile, diabetes duration, waist circumference, age, and index HbA1c showed significant associations with TCNS. CONCLUSIONS:Our study suggests that individuals with T2DM who exhibit more severe carotid atherosclerosis may not only be at increased risk of developing DSPN but also may experience greater severity of DSPN. PI in both the CCA and ICA, along with the CPS, serve as surrogate biomarkers for DSPN severity.
10.3390/diagnostics14171922
Lipoprotein-associated phospholipase A2 adds to risk prediction of incident coronary events by C-reactive protein in apparently healthy middle-aged men from the general population: results from the 14-year follow-up of a large cohort from southern Germany.
Koenig Wolfgang,Khuseyinova Natalie,Löwel Hannelore,Trischler Gerlinde,Meisinger Christa
Circulation
BACKGROUND:Chronic inflammation represents an essential feature of the atherosclerotic process. Lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme mainly produced by monocytes/macrophages, generates potent proinflammatory products. METHODS AND RESULTS:Plasma concentrations of Lp-PLA2 were determined by ELISA in 934 apparently healthy men aged 45 to 64 years sampled from the general population in 1984 and followed up until 1998. During this period, 97 men experienced a coronary event diagnosed according to the MONICA (MONItoring of trends and determinants in CArdiovascular disease) protocol. Baseline levels of Lp-PLA2 were higher in subjects who experienced an event than in event-free subjects (295+/-113 versus 263+/-79 ng/mL, P<0.01). Lp-PLA2 was positively correlated with total cholesterol (R=0.30, P<0.0001) and age (R=0.12, P=0.001), was only slightly correlated with HDL cholesterol (R=0.09, P=0.005) and C-reactive protein R=0.06, P=0.06), but was not correlated with body mass index or blood pressure. In a Cox model, a 1-SD increase in Lp-PLA2 was associated with risk of future coronary events (hazard ratio [HR] 1.37, 95% CI 1.16 to 1.62). After controlling for potential confounders, the HR was attenuated but remained statistically significant (HR 1.23, 95% CI 1.02 to 1.47). Further inclusion of C-reactive protein in the model did not appreciably affect its predictive ability (HR 1.21, 95% CI 1.01 to 1.45). CONCLUSIONS:Elevated levels of Lp-PLA2 appeared to be predictive of future coronary events in apparently healthy middle-aged men with moderately elevated total cholesterol, independent of CRP. This suggests that Lp-PLA2 and CRP may be additive in their ability to predict risk of coronary heart disease.
10.1161/01.CIR.0000143377.53389.C8
Monocyte to HDL ratio: a novel marker of resistant hypertension in CKD patients.
Gembillo Guido,Siligato Rossella,Cernaro Valeria,Satta Ersilia,Conti Giovanni,Salvo Antonino,Romeo Adolfo,Calabrese Vincenzo,Sposito Giovanna,Ferlazzo Guido,Santoro Domenico
International urology and nephrology
BACKGROUND:Inflammation, oxidative stress (OS), atherosclerosis and resistant hypertension (RH) are common features of chronic kidney disease (CKD) leading to a higher risk of death from cardiovascular disease. These effects seem to be modulated by impaired anti-oxidant, anti-inflammatory and reverse cholesterol transport actions of high-density lipoprotein cholesterol (HDL). HDL prevents and reverses monocyte recruitment and activation into the arterial wall and impairs endothelial adhesion molecule expression. Recently, monocyte count to HDL-cholesterol ratio (MHR) has emerged as a potential marker of inflammation and OS, demonstrating to be relevant in CKD. Our research was aimed to assess, for the first time, its reliability in RH. METHODS:We performed a retrospective study on 214 patients with CKD and arterial hypertension who were admitted between January and June 2019 to our Department, 72 of whom were diagnosed with RH. RESULTS:MHR appeared inversely related to eGFR (ρ = - 0.163; P = 0.0172). MHR was significantly higher among RH patients compared to non-RH ones (12.39 [IQR 10.67-16.05] versus 7.30 [5.49-9.06]; P < 0.0001). Moreover, MHR was significantly different according to the number of anti-hypertensive drugs per patient in the whole study cohort (F = 46.723; P < 0.001) as well as in the non-RH group (F = 14.191; P < 0.001). Moreover, MHR positively correlates with diabetes mellitus (ρ = 0.253; P = 0.0002), white blood cells (ρ = 0.664; P < 0.0001) and C-reactive protein (ρ = 0.563; P < 0.0001). CONCLUSIONS:MHR may be a reliable biomarker due to the connection between HDL and monocytes. Our study suggests that MHR is linked with the use of multiple anti-hypertensive therapy and resistant hypertension in CKD patients, and can be a useful ratio to implement appropriate treatment strategies.
10.1007/s11255-021-02904-9
The predictive value of the hs-CRP/HDL-C ratio, an inflammation-lipid composite marker, for cardiovascular disease in middle-aged and elderly people: evidence from a large national cohort study.
Lipids in health and disease
BACKGROUND AND AIMS:Cardiovascular disease (CVD) is associated with inflammation and abnormal lipid metabolism. However, a single inflammatory index or a single lipid index cannot accurately predict the prognosis of CVD independently because it is prone to be affected by various confounding factors. METHODS:This population-based cohort study included 6,554 participants from the China Health and Retirement Longitudinal Study (CHARLS) to investigate correlations. In the present study, the occurrence of CVD events such as stroke and heart disease was evaluated by considering self-reported diagnoses at the beginning of the study and during wave 4, and a restricted cubic spline model was used to investigate potential nonlinear relationships in addition to multivariate logistic regression models. Stratified analyses were performed to examine how sociodemographic characteristics may influence the results. RESULTS:Seven years of follow-up (2011-2018) revealed that 786 people (11.99%) developed CVD. According to the adjusted model, the high-sensitivity C-reactive protein (hs-CRP)-to-high-density lipoprotein cholesterol (HDL-C) ratio is a contributing factor to CVD risk (OR 1.31, 95% CI 1.05-1.64). In addition, a nonlinear relationship was observed between the hs-CRP/HDL-C ratio and the occurrence of new CVD, stroke, or cardiac issues (P <0.05, <0.05). Moreover, noteworthy associations between the hs-CRP/HDL-C ratio and age were detected in the stratified analysis (P = 0.048), indicating that younger participants had more negative effects of a high hs-CRP/HDL-C ratio. CONCLUSIONS:According to the present cohort study, a high hs-CRP/HDL-C ratio is a significant risk factor for CVD, new stroke, and heart problems. Early intervention in patients with increased hs-CRP/HDL-C ratios may further reduce the incidence of CVD, in addition to focusing on independent lipid markers or independent inflammatory markers.
10.1186/s12944-024-02055-7
Association of Monocyte-to-HDL Cholesterol Ratio with Slow Coronary Flow is Linked to Systemic Inflammation.
Canpolat Ugur,Çetin Elif Hande,Cetin Serkan,Aydin Selahattin,Akboga Mehmet Kadri,Yayla Cagri,Turak Osman,Aras Dursun,Aydogdu Sinan
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
BACKGROUND:Previous studies proposed that both inflammation, oxidative stress, and impaired endothelial dysfunction have a significant role in occurrence of slow coronary flow (SCF). monocyte-to-high density lipoprotein cholesterol ratio (MHR) is a recently emerged indicator of inflammation and oxidative stress, which have been studied only in patients with chronic kidney disease. HYPOTHESIS:We aimed to assess the relationship between MHR and SCF. METHODS:Patients who had angiographically normal coronary arteries were enrolled in this retrospective study (n = 253 as SCF group and n = 176 as control group). Patients who had corrected thrombolysis in myocardial infarction frame counts (cTFCs) above the normal cutoffs were defined as with SCF. RESULTS:The MHR and high-sensitivity C-reactive protein (hsCRP) were significantly higher in the SCF group. In correlation analysis, MHR has a significantly positive correlation with cTFC and serum hsCRP levels (P < .001). In multivariate logistic regression analysis, MHR was found as independently associated with the presence of SCF (odds ratio: 1.24, P < .001). CONCLUSION:Higher MHR which indicates an enhanced inflammation and oxidative stress was significantly and independently associated with the presence of SCF. Besides, MHR was positively correlated with serum hsCRP level as a conventional marker for systemic inflammation.
10.1177/1076029615594002
New atherogenic index for the prediction of carotid atherosclerosis based on the non-ultrasensitive c-reactive protein/HDL ratio.
Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis
INTRODUCTION:Current guidelines recommend cardiovascular risk assessment as a preventive measure for cardiovascular diseases, whose fundamental etiology is arteriosclerosis. One of the tools used to estimate risk in clinical practice are atherogenic indices (AI), ratios between lipid fractions with well-established reference ranges. Despite its widespread use, there is still limited information on its clinical utility. In recent years, some research has reinforced the role of inflammation in the etiology and chronicity of the atherosclerotic process. The inclusion of inflammatory parameters in the AI calculation could improve its diagnostic performance in the detection of arteriosclerosis. We sought to evaluate a new AI as a ratio between C-reactive protein (CRP) values and high-density lipoprotein cholesterol (HDL) values. METHODS:A total of 282 asymptomatic patients with no history of cardiovascular disease were included in the study. Laboratory tests with lipid profile and CRP, and carotid ultrasound to assess the presence of atheromatosis were performed in all of them. The new AI is established as the ratio between non-ultrasensitive CRP value in mg/dL (multiplied by 100) and HDL value in mg/dL. It was compared with the Castelli I and II indices, and the plasma atherogenic index. The optimal cut-off point of the new AI was value=1 as determined by ROC curve, with an area under the curve of 0.678 (95% CI 0.60-0.75; p<0.001). RESULTS:Mean age of patients was 60.4±14.5 years. A total of 118 patients (41.8% of total) had carotid arteriosclerosis. When evaluating the diagnostic performance of different AIs, we found that CRP·100/HDL ratio showed the highest values of sensitivity and positive predictive value (0.73 and 0.68, respectively) compared to the Castelli I and II indices, and the plasma atherogenic index. It was also the only predictor of carotid atheromatosis both when considering its values quantitatively (with OR 1.4 [95% CI 1.1-1.7]; p=0.005), and qualitatively (with OR 2.9 [95% CI 1.5-5.5]; p<0.001) in patients with a CRP·100/HDL ratio>1. CONCLUSIONS:The new PCR·100/HDL index showed the best diagnostic performance in the detection of carotid atheromatosis compared to other classic AIs in this Spanish population of asymptomatic patients.
10.1016/j.arteri.2023.07.002
Evaluation of monocyte to HDL cholesterol ratio and other inflammatory markers in patients with psoriasis.
Sirin Mumtaz Cem,Korkmaz Selma,Erturan Ijlal,Filiz Basak,Aridogan Buket Cicioglu,Cetin Emel Sesli,Yildirim Mehmet
Anais brasileiros de dermatologia
BACKGROUND:Psoriasis is a chronic systemic inflammatory disease frequently associated with serious comorbidities. OBJECTIVES:To investigate the systemic inflammatory burden in psoriasis and to assess the correlation between traditional and novel inflammatory markers and the severity of the disease. METHODS:This cross-sectional study was conducted on 60 patients with psoriasis vulgaris and 50 healthy volunteers. Data including demographics, Psoriasis Area and Severity Index scores, and laboratory results were analyzed and compared. RESULTS:Compared with the control group, the psoriatic patients had significantly higher high sensitive C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, leukocyte, neutrophil, neutrophil-to-lymphocyte ratio, monocyte to high density lipoprotein (HDL) cholesterol ratio, and aspartate aminotransferase levels, and significantly lower HDL cholesterol levels (p < 0.05). No significant difference was found in procalcitonin, lymphocyte, monocyte, hemoglobin, red blood cell distribution width, platelet, mean platelet volume, platelet distribution width, lymphocyte-to-monocyte ratio, anti-cyclic citrullinated peptide, glucose, alanine aminotransaminase, blood urea nitrogen, creatinine, triglyceride, total cholesterol, and LDL cholesterol levels between the two groups (p > 0.05). The Psoriasis Area and Severity Index score was positively correlated with high-sensitivity C-reactive protein, serum amyloid A, and monocyte to HDL cholesterol ratio, and negatively correlated with lymphocyte-to-monocyte ratio (p < 0.05). STUDY LIMITATIONS:This was a single-center study with relatively limited numbers of patients and controls. CONCLUSIONS:The data show that high sensitivity C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and monocyte to HDL cholesterol ratio can be used as markers of systemic inflammation in patients with psoriasis. Moreover, high sensitivity C-reactive protein, serum amyloid A, monocyte to HDL cholesterol ratio and lymphocyte-to-monocyte ratio are closely related to the Psoriasis Area and Severity Index score, and they may be regarded as objective indicators in determining the disease severity.
10.1016/j.abd.2020.02.008
C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction.
Ridker P M,Glynn R J,Hennekens C H
Circulation
BACKGROUND:C-reactive protein (CRP) is a sensitive marker of inflammation, and elevated levels have been associated with future risk of myocardial infarction (MI). However, whether measurement of CRP adds to the predictive value of total cholesterol (TC) and HDL cholesterol (HDL-C) in determining risk is uncertain. METHODS AND RESULTS:Among 14916 apparently healthy men participating in the Physicians' Health Study, baseline levels of CRP, TC, and HDL-C were measured among 245 study subjects who subsequently developed a first MI (cases) and among 372 subjects who remained free of cardiovascular disease during an average follow-up period of 9 years (controls). In univariate analyses, high baseline levels of CRP, TC, and TC:HDL-C ratio were each associated with significantly increased risks of future MI (all P values <0.001). In multivariate analyses, models incorporating CRP and lipid parameters provided a significantly better method to predict risk than did models using lipids alone (all likelihood ratio test P values <0.003). For example, relative risks of future MI among those with high levels of both CRP and TC (RR=5.0, P=0.0001) were greater than the product of the individual risks associated with isolated elevations of either CRP (RR=1.5) or TC (RR=2.3). In stratified analyses, baseline CRP level was predictive of risk for those with low as well as high levels of TC and the TC:HDL-C ratio. These findings were virtually identical in analyses limited to nonsmokers and after control for other cardiovascular risk factors. CONCLUSIONS:In prospective data from a large cohort of apparently healthy men, baseline CRP level added to the predictive value of lipid parameters in determining risk of first MI.
10.1161/01.cir.97.20.2007
Association of Three Novel Inflammatory Markers: Lymphocyte to HDL-C Ratio, High-Sensitivity C-Reactive Protein to HDL-C Ratio and High-Sensitivity C-Reactive Protein to Lymphocyte Ratio With Metabolic Syndrome.
Endocrinology, diabetes & metabolism
OBJECTIVE:We aimed to compare the association of three novel inflammatory indicators with metabolic syndrome (MetS) among Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort participants. METHODS:According to the International Diabetes Federation (IDF) criteria, the cohort participants were divided into the MetS(+) and MetS(-) groups. The lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR), high-sensitivity C-reactive protein (hs-CRP) to HDL-C ratio (HCHR) and hs-CRP to lymphocyte ratio (HCLR) were calculated and were compared between the groups. Binary logistic regression (LR) analysis was performed to find the association of the indices with the presence of MetS among men and women. Receiver-operating characteristic (ROC) curve analysis was used to establish cut-off values in predicting MetS for men and women. p-Values <0.05 were considered as statistically significant. RESULTS:Among a total of 8890 participants (5500 MetS(-) and 3390 MetS(+)), LHR, HCHR and HCLR were significantly higher in the MetS(+) group than in MetS(-) group (p < 0.001). In LR analysis, after adjusting for multiple cofounders, LHR remained an independent factor for the presence of MetS among men (OR: 1.254; 95% CI: 1.202-1.308; p < 0.001) and women (OR: 1.393; 95% CI: 1.340-1.448; p < 0.001). HCHR also remained an independent factor for the presence of MetS only in women (OR: 1.058; 95% CI: 1.043-1.073; p < 0.001). ROC curve analysis showed that LHR had the higher AUC for predicting MetS in both men (AUC: 0.627; 95% CI: 0.611-0.643; p < 0.001) and women (AUC: 0.683; 95% CI: 0.670, 0.696; p < 0.001). CONCLUSION:This suggests that among both genders, the LHR as an inexpensive and easy-to-access marker has a better diagnostic performance and could be a promising alternative to the traditional expensive inflammatory markers such as hs-CRP for the evaluation of inflammation in patients with MetS.
10.1002/edm2.479
Relation Between Monocyte to High-Density Lipoprotein Cholesterol Ratio With Presence and Severity of Isolated Coronary Artery Ectasia.
Kundi Harun,Gok Murat,Kiziltunc Emrullah,Cetin Mustafa,Cicekcioglu Hulya,Cetin Zehra Guven,Karayigit Orhan,Ornek Ender
The American journal of cardiology
The aim of this study was to investigate an easily available inflammatory and oxidative stress marker and monocyte to high-density lipoprotein cholesterol ratio (MHR) in patients with coronary artery ectasia (CAE). The study population included 405 patients of which 135 patients had isolated CAE, 135 patients had obstructive coronary artery disease (CAD), and 135 patients had normal coronary angiograms (NCAs). The severity of isolated CAE was determined according to the Markis classification. The MHR was significantly greater in patients with isolated CAE than those with obstructive CAD and NCAs: 14.8 (11.6 to 19.8), 11.4 (9.6 to 13.5), 9.8 (7.5 to 11.9), respectively. Linear regression analyses showed that MHR and C-reactive protein were significantly related with the severity of isolated CAE. In conclusion, the MHR is significantly greater in patients with CAE compared to controls with obstructive CAD and NCAs, and MHR is associated with the severity of CAE.
10.1016/j.amjcard.2015.08.036
Serum cystatin C levels are associated with triglycerides/high-density lipoprotein cholesterol ratio in adolescent girls ages between 16-19 years old.
Klisic A,Kavaric N,Ninic A
European review for medical and pharmacological sciences
OBJECTIVE:The pathophysiological role of cystatin C in cardiometabolic disorders is not completely explored in young population. On the other hand, together with the increase in obesity, dyslipidemia and insulin resistance (IR) are often observed even in youngsters. The aim of the study was to investigate the relationship between cystatin C and triglycerides-to-high-density lipoprotein cholesterol ratio (TG/HDL-c), as an indicator of dyslipidemia and a surrogate marker of IR in the cohort of adolescent girls ages between 16-19 years. PATIENTS AND METHODS:A total of 99 girls were included in the study. Anthropometric and biochemical parameters were provided. Associations of biochemical markers with TG/HDL-c ratio were tested using univariable and multivariable ordinal regression analysis for TG/HDL-c ratio tertiles as dependent variable. RESULTS:In univariate analysis, cystatin C levels were significantly associated with TG/HDL-c ratio (OR=1.813; 95% CI: 1.190-2.757, p=0.005). Furthermore, multivariate analysis revealed that cystatin C was an independent predictor of TG/HDL-c ratio when body mass index and high sensitivity C-reactive protein (i.e., markers that were significantly correlated with TG/HDL-c ratio in Spearman's correlation analysis) were included in the Model. Adjusted odds for cystatin C (OR=1.621; 95% CI: 1.028-2.552, p=0.037) demonstrated that rise in cystatin C by 0.1 mg/L increased the probability for higher TG/HDL-c tertile group by 1.621 times. CONCLUSIONS:Serum cystatin C levels are associated with TG/HDL-c ratio in adolescent girls. Longitudinal studies are needed to confirm the causal relationship between cystatin C and TG/HDL-c ratio and to further explore its diagnostic and therapeutic potential in dyslipidemia and insulin resistance in young population.
10.26355/eurrev_202010_23426
Is elevated high-density lipoprotein cholesterol always good for coronary heart disease?
Sun Yuhua,Yang Yuejin,Pei Weidong,Wu Yongjian,Zhao Jinglin
Clinical cardiology
BACKGROUND:High-density lipoprotein (HDL) could enhance inflammation in atherogenesis when inflammatory response is present, and the activity of paraoxonase and antioxidant in HDL in the elderly is significantly decreased. There might be a different role for high-density lipoprotein cholesterol (HDL-C) between different age groups in patients with coronary heart disease (CHD). METHODS:For this study, 225 inpatients with CHD (coronary atherosclerosis stenosis >/= 50% on >/= 1 major coronary arteries by coronary angiography), and 80 without CHD; 120 resting unstable angina patients, and 68 with stable angina were consecutively recruited. Risk factors were analyzed for CHD and resting unstable angina. RESULTS:High-density lipoprotein cholesterol in resting unstable angina was higher than that in stable angina (1.24 +/- 1.05 versus 1.05 +/- 0.29 mmol/L, p = 0.032). After adjustment for age, sex, physical inactivity, hypertension, diabetes, C-reactive protein, triglycerides, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) the adjusted odds ratio (OR) (95% CI) of resting unstable angina was 10.19 (2.18-47.6, p = 0.003) for HDL-C. Risk factors were further investigated in different age groups. Adjusted OR of CHD associated with HDL-C in < 55-year-old group was 0.09 (0.01-0.66, p = 0.018), in >/= 55-year-old group it was 0.55 (0.08-3.82, p > 0.05). Adjusted OR of resting unstable angina associated with high HDL-C was 19.24 (2.86-129.4, p = 0.002) in patients aged >/= 55 years. CONCLUSIONS:Elevated HDL-C might be an independent risk factor for resting unstable angina, even though HDL-C could play a much more important role in protection against coronary stenosis in younger or middle-aged persons.
10.1002/clc.20137
Inflammation and atherosclerosis: the value of the high-sensitivity C-reactive protein assay as a risk marker.
Jialal I,Devaraj S
American journal of clinical pathology
C-reactive protein (CRP) is a prototypic marker of inflammation. Numerous prospective studies in healthy volunteers have confirmed that high-sensitivity CRP (hsCRP) predicts cardiovascular events (CVEs), and hsCRP seems additive to an elevated total cholesterol level and a total/high-density lipoprotein cholesterol ratio in men and women in predicting risk. In smokers and people with metabolic syndrome, hsCRP levels are elevated; in elderly people, there seems to be a relationship between hsCRP and CVEs and mortality. Several properties of CRP make it proatherogenic; however; pending further studies, it should be considered as a risk marker. In people with acute coronary syndromes, hsCRP measurement may be valuable. Elevated levels in the highest quantile seem to predict greater mortality and poorer prognosis in patients with unstable angina and myocardial infarction (MI). While hsCRP is a strong independent predictor of risk of future MI, stroke, peripheral arterial disease, and vascular death, the validity of hsCRP as a risk marker needs to be assessed in all populations. Weight loss, statin drugs, aspirin, and high-dose alpha tocopherol therapy could affect hsCRP. It has its greatest validity as an adjunctive measure in the primary prevention of cardiovascular disease.
10.1309/J63V-5LTH-WYFC-VDR5
Association of monocyte-to-high density lipoprotein-cholesterol ratio with peripheral neuropathy in patients with Type II diabetes mellitus.
Gökçay Canpolat Asena,Emral Rıfat,Keskin Çağlar,Canlar Şule,Şahin Mustafa,Çorapçioğlu Demet
Biomarkers in medicine
We assessed the association of monocyte count to high-density lipoprotein cholesterol ratio (MHR) with diabetic peripheral neuropathy (DPN) and its role as a marker for identification of high-risk patients for DPN. A total of 180 patients with Type II diabetes mellitus (T2DM) were enrolled in the study. MHR, erythrocyte sedimentation rate and serum CRP along with other tests for T2DM and DPN were measured. Duration of T2DM (p = 0.013), insulin use (p = 0.006) and serum CRP levels (p = 0.008) were significantly higher in patients with DPN. MHR was similar between groups (p = 0.447). Duration of diabetes (OR: 1.048; p = 0.038) and the serum CRP levels (OR: 1.073; p = 0.026) were found as independent predictors for the presence of DPN, however, MHR was not. Higher MHR indicates an enhanced inflammation and oxidative stress which was not found to be associated with the presence of DPN.
10.2217/bmm-2018-0451
The blood monocyte to high density lipoprotein cholesterol ratio (MHR) is a possible marker of carotid artery plaque.
Lipids in health and disease
BACKGROUND:MHR is the ratio of monocyte to high-density lipoprotein cholesterol (HDL-C). It has been reported that MHR changes are associated with cardiovascular and cerebrovascular disease. Carotid plaque is a common vascular lesion of the carotid artery and is a manifestation of atherogenesis. This study investigated the relationships between the MHR and the incidence of carotid plaques. METHODS:The data of 3848 physical examiners were analyzed for retrospective analysis, which included 1428 patients with noncarotid plaque, 1133 patients with single carotid plaque, and 1287 patients with bilateral or multiple carotid plaques. Statistical analysis was performed on SPSS 22.0 0 software and statistical software R and its GAM package. RESULTS:The difference was statistically significant in the levels of MHR, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), blood lipids (HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (Tg)), blood glucose (Glu), hemoglobin A1c (HbA1c), renal function (urea, creatinine (Crea)), estimated glomerular filtration rate (eGFR), and uric acid (Ua) in the carotid plaque groups (P < 0.001, respectively). There was no significant difference between the sex (P = 0.635) and age (P = 0.063) in the different groups. MHR levels were positively correlated with BMI (r = 0.364, P < 0.001), hs-CRP (r = 0.320, P < 0.001), Tg (r = 0.417, P < 0.001), Crea (r = 0.323, P < 0.001), eGFR (r = - 0.248, P < 0.001), Ua (r = 0.383, P < 0.001) and HbA1c (r = 0.197, P < 0.001). Levels of TC, Glu, and urea were slightly correlated with the MHR level (r = - 0.150, P < 0.001; r = 0.187, P < 0.001; r = 0.137, P < 0.001, respectively). The MHR level increased with elevated severity of carotid plaque in subjects without hypertension or diabetes (P < 0.001). In adjusted models, with the rise of MHR level, the probability of occurrence of carotid plaque had a 1.871-fold (95% CI: 1.015-3.450, P = 0.045) increase; the probability of multiple occurrences of carotid plaques had a 2.896-fold (95% CI: 1.415-5.928, P < 0.001) increase. The GAM curve showed a nonlinear correlation between the normalized MHR and the probability of carotid plaque occurrence. CONCLUSIONS:MHR could be used as a possible marker for plaque formation and severity.
10.1186/s12944-022-01741-8
Elevated C-reactive Protein and Depressed High-density Lipoprotein Cholesterol are Associated with Poor Function Outcome After Ischemic Stroke.
Zheng Xiaowei,Zeng Nimei,Wang Aili,Zhu Zhengbao,Zhong Chongke,Xu Tan,Xu Tian,Peng Yanbo,Peng Hao,Li Qunwei,Ju Zhong,Geng Deqin,Zhang Yonghong,He Jiang
Current neurovascular research
AIMS:C-reactive protein is an established marker of inflammation that can impair the protective function of High Density Lipoprotein Cholesterol (HDL-C). The combined effect of Creactive protein and HDL-C on long-term outcomes in patients with stroke remains uncertain. METHODS:A total of 3124 acute ischemic stroke subjects from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) were included in this analysis. Participants were divided into four groups according to CRP and HDL-C levels on admission. The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at one year after stroke. RESULTS:Compared to participants with low CRP/ high HDL-C, adjusted odd ratios for primary outcome for those with low CRP /low HDL-C, high CRP /high HDL-C and high CRP /low HDL-C were 1.06(0.81-1.39),1.78(1.31-2.41) and 2.03(1.46-2.80), respectively, after multiple adjustments. Adding serum CRP and HDL-C status to a model containing conventional stroke risk factors significantly improve risk reclassification for the combined outcome of death and major disability (NRI: 6.85%, P=0.005; IDI: 2.57%, P=0.002). Moreover, no interaction was observed between CRP and HDL-C in relation to stroke outcomes (P-interaction >0.05 for all). CONCLUSIONS:High CRP with low HDL-C levels was associated with death and major disability within one year after ischemic stroke. The findings suggest that the ischemic patients with both high CRP and low HDL-C should be treated with reducing CRP and promoting HDL-C levels.
10.2174/1567202615666180712100440
High triglyceride to high-density lipoprotein cholesterol ratio and arterial stiffness in postmenopausal Korean women.
Chung Tae-Ha,Shim Jae-Yong,Kwon Yu-Jin,Lee Yong-Jae
Journal of clinical hypertension (Greenwich, Conn.)
The ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) is positively linked to insulin resistance, and it has emerged as an independent predictor of cardiovascular disease. Menopause is characterized by various detrimental metabolic and vascular changes that may lead to high TG with low HDL cholesterol and arterial stiffness. Several epidemiological studies have reported that high TG/HDL ratio has a positive association with arterial stiffness in both adult and adolescent populations; it is not known whether TG/HDL ratio is related to brachial-ankle PWV (baPWV) in postmenopausal women. Thus, the authors aimed to investigate the association between TG/HDL ratio and arterial stiffness as measured by baPWV in 434 postmenopausal women. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for high baPWV were calculated after adjusting for confounding variables across TG/HDL ratio quartiles using multiple logistic regression analysis. The mean values of meaningful cardiometabolic variables increased with TG/HDL ratio quartiles. The adjusted baPWV (SEs) significantly increased with TG/HDL quartiles: Q1 = 1412 (22.1), Q2 = 1469 (21.4), Q3 = 1482 (21.0), and Q4 = 1505 (21.6) cm/s after adjusting for age, body mass index (BMI), and systolic blood pressure. The OR (95% CI) of the highest TG/HDL ratio quartile as compared to the lowest TG/HDL ratio quartile for high PWV was 2.77 (1.16-6.63) after adjusting for age, BMI, smoking status, regular exercise, mean arterial pressure, fasting plasma glucose, total cholesterol level, hypertension, log-transformed C-reactive protein, and the use of antihypertensive and lipid-lowering drugs. The TG/HDL ratio was positively and independently associated with arterial stiffness in postmenopausal Korean women.
10.1111/jch.13484
Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1.
Journal of lipid research
Atherosclerosis results from the deposition and oxidation of LDL and immune cell infiltration in the sub-arterial space leading to arterial occlusion. Studies have shown that transcytosis transports circulating LDL across endothelial cells lining blood vessels. LDL transcytosis is initiated by binding to either scavenger receptor B1 (SR-B1) or activin A receptor-like kinase 1 on the apical side of endothelial cells leading to its transit and release on the basolateral side. HDL is thought to partly protect individuals from atherosclerosis due to its ability to remove excess cholesterol and act as an antioxidant. Apolipoprotein A1 (APOA1), an HDL constituent, can bind to SR-B1, raising the possibility that APOA1/HDL can compete with LDL for SR-B1 binding, thereby limiting LDL deposition in the sub-arterial space. To examine this possibility, we used in vitro approaches to quantify the internalization and transcytosis of fluorescent LDL in coronary endothelial cells. Using microscale thermophoresis and affinity capture, we find that SR-B1 and APOA1 interact and that binding is enhanced when using the cardioprotective variant of APOA1 termed Milano (APOA1-Milano). In male mice, transiently increasing the levels of HDL reduced the acute deposition of fluorescently labeled LDL in the atheroprone inner curvature of the aorta. Reduced LDL deposition was also observed when increasing circulating wild-type APOA1 or the APOA1-Milano variant, with a more robust inhibition from the APOA1-Milano. The results suggest that HDL may limit SR-B1-mediated LDL transcytosis and deposition, adding to the mechanisms by which it can act as an atheroprotective particle.
10.1016/j.jlr.2024.100530
Monocyte to high-density lipoprotein ratio presents a linear association with atherosclerosis and nonlinear association with arteriosclerosis in elderly Chinese population: The Northern Shanghai Study.
Nutrition, metabolism, and cardiovascular diseases : NMCD
BACKGROUND AND AIMS:Inflammation closely correlates with atherosclerosis and cardiovascular disease (CVD). Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammation index that can be obtained by routine blood tests. We aimed to investigate the associations between MHR and atherosclerosis and arteriosclerosis. METHODS AND RESULTS:We enrolled 2451 participants from the Northern Shanghai Study. Atherosclerosis (carotid plaque (CP), lower extremity atherosclerotic (LEA) assessed by ankle-brachial index) and arteriosclerosis (arterial stiffness (AS) assessed by carotid-femoral pulse wave velocity) were measured using standard methods. In the univariable logistic regression model, higher MHR was significantly associated with increased AS, CP, and LEA risk. In the multivariable logistic regression model, after adjustment for age, sex, hypertension, diabetes mellitus, body mass index, smoking habit, low-density lipoprotein cholesterol, and family history of premature CVD, quartile 4 (Q4) of MHR was associated with an increased risk of AS (odds ratio (OR) = 1.41; 95% confidence interval (CI):1.05-1.88; P = 0.036), CP (OR = 1.35; 95%CI:1.04-1.77; P = 0.044), and LEA (OR = 2.23; 95%CI:1.49-3.35; P < 0.001). Similar results were observed when MHR was analyzed as a continuous variable. The restricted cubic spline (RCS) curve showed that the association between MHR and AS was nonlinear (P = 0.021), but not LEA (P = 0.177) or CP (P = 0.72). CONCLUSION:MHR presents a linear association with atherosclerosis and a nonlinear association with arteriosclerosis in the elderly Chinese population. These findings may indicate the need for early assessment and intervention for inflammation. The registration number for clinical trials: NCT02368938.
10.1016/j.numecd.2022.12.002
Combination model of neutrophil to high-density lipoprotein ratio and system inflammation response index is more valuable for predicting peripheral arterial disease in type 2 diabetic patients: A cross-sectional study.
Frontiers in endocrinology
Background:Neutrophil/high-density lipoprotein (HDL) ratio (NHR), monocyte/HDL ratio (MHR), lymphocyte/HDL ratio (LHR), platelet/HDL ratio (PHR), systemic immune-inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) have been recently investigated as novel inflammatory markers. Herein, the correlation was investigated between these inflammatory biomarkers and peripheral arterial disease (PAD) in type 2 diabetes mellitus (T2DM) patients. Methods:In this retrospective observational study, the hematological parameter data of 216 T2DM patients without PAD (T2DM-WPAD) and 218 T2DM patients with PAD (T2DM-PAD) at Fontaine stages II, III or IV stage had been collected. Differences in NHR, MHR, LHR, PHR, SII, SIRI, and AISI were analyzed, and receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of these parameters. Results:The levels of NHR, MHR, PHR, SII, SIRI and AISI in T2DM-PAD patients were significantly higher than in T2DM-WPAD patients ( < 0.001). They were correlated with disease severity. Further, multifactorial logistic regression analyses showed that higher NHR, MHR, PHR, SII, SIRI, and AISI might be independent risk factors for T2DM-PAD ( < 0.001). The areas under the curve (AUCs) of the NHR, MHR, PHR, SII, SIRI, and AISI for T2DM-PAD patients was 0.703, 0.685, 0.606, 0.648, 0.711, and 0.670, respectively. The AUC of the NHR and SIRI combined model was 0.733. Conclusion:The levels of NHR, MHR, PHR, SII, SIRI, and AISI were higher in T2DM-PAD patients, and they were independently linked with its clinical severity. The combination model of NHR and SIRI was most valuable for predicting T2DM - PAD.
10.3389/fendo.2023.1100453
Non-linear association of the platelet/high-density lipoprotein cholesterol ratio with bone mineral density a cross-sectional study.
Lipids in health and disease
BACKGROUND:Numerous studies have demonstrated shared risk factors and pathophysiologic mechanisms between osteoporosis and cardiovascular disease. High-density lipoprotein cholesterol (HDL-C) and platelets have long been recognized as crucial factors for cardiovascular health. The platelet to HDL-C ratio (PHR) combines platelet count and high-density lipoprotein cholesterol (HDL-C) level, It is a novel biomarker for metabolic syndrome and cardiovascular disease. The platelet to HDL-C ratio (PHR) possibly reflects the balance between proinflammatory and anti-inflammatory states in the body. Therefore, we hypothesized that changes in PHR ratios may predict a predisposition to pro-inflammatory and increased bone resorption. However, the relationship between the platelet to HDL-C ratio (PHR) and bone mineral density (BMD) remains insufficiently understood. This study aimed to elucidate the relationship between the platelet to HDL-C ratio (PHR) index and bone mineral density (BMD). METHODS:Data from the NHANES 2005-2018 were analyzed, excluding adults with missing key variables and specific conditions. Nonlinear relationships were explored by fitting smoothed curves and generalized additive models, with threshold effects employed to calculate inflection points. Additionally, subgroup analyses and interaction tests were conducted. RESULTS:The study included 13,936 individuals with a mean age of 51.19 ± 16.65 years. Fitted smoothed curves and generalized additive models revealed a nonlinear, inverted U-shaped relationship between the two variables. Threshold effect analysis showed a significant negative association between PHR and total femur bone mineral density (BMD) beyond the inflection point of platelet to HDL-C ratio (PHR) 33.301. Subgroup analyses showed that a significant interaction between these two variables was observed only in the age and sex subgroups (P-interaction < 0.05). CONCLUSIONS:Our study identified a complex, nonlinear, inverted U-shaped relationship between platelet to HDL-C ratio (PHR) and total femur bone mineral density (BMD). These findings underscore the importance of maintaining optimal PHR levels to support bone health, especially in high-risk populations.
10.1186/s12944-024-02291-x
Association of 28-day mortality with non-high-density lipoprotein cholesterol and the high-density lipoprotein cholesterol ratio (NHHR) in patients with sepsis: Results of MIMIC-IV database analysis.
Lipids in health and disease
BACKGROUND:The correlation between lipid profiles and sepsis has received increasing attention. The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is one of the key lipid profiles. However, in-depth exploration of the correlation between NHHR and the mortality risk of patients with sepsis is limited. METHODS:Data from the MIMIC-IV (v2.2) database, we review the NHHR relevance and the sepsis severity index using Spearman's correlation analysis. Additionally, we research NHHR associated with sepsis patients' survival rate of 28 days using Cox regression analyses of continuous and categorical models. To further validate our findings, we conducted subgroup and sensitivity analyses. RESULTS:The study involved 3,142 patients diagnosed with sepsis, according to 28 days after in-hospital survival condition, divided into two groups. In this study, 2932 patients were in the survival group and 210 patients died within 28 days (mortality group). Of note, the mean NHHR of patients in the mortality group exceeded that of the survival group (3.5 vs. 2.9). Additionally, NHHR was positively correlated with the severity index. After adjusting for demographic and laboratory data, an increased NHHR was positively correlated with higher sepsis mortality risk (OR = 1.06; 95% CI: 1.02-1.11; P = 0.013). Subgroup analysis shown the same results. Contributors were be categorized into two groups based on NHHR levels, with a threshold of 2.61. Contrast the mortality risk between low-NHHR group and high-NHHR group, high-NHHR show greater mortality risk on 28-day, 60-day, 90-day, in ICU, and in hospital. CONCLUSION:Elevated NHHR is to be correlated with an increased risk of mortality in patients with sepsis. Further research on NHHR may contribute to advancements in sepsis prevention and treatment.
10.1186/s12944-024-02219-5
Remnant cholesterol/high-density lipoprotein cholesterol ratio is a new powerful tool for identifying non-alcoholic fatty liver disease.
Zou Yang,Hu Chong,Kuang Maobin,Chai Yuliang
BMC gastroenterology
BACKGROUND:Remnant cholesterol/high-density lipoprotein cholesterol (RC/HDL-C) ratio has been shown to be a good predictor of metabolic disease risk, but no studies have further investigated the role of RC/HDL-C ratio in non-alcoholic fatty liver disease (NAFLD) patients. METHODS:The participants were 14,251 adults who underwent a physical examination, all of whom underwent abdominal ultrasonography to determine whether they had NAFLD. Receiver operating characteristic curve analysis and multivariate logistic regression models were used to assess the association between the RC/HDL-C ratio and the risk of NAFLD. RESULTS:Multivariate logistic regression analysis showed that after fully adjusting the confounding factors, the higher RC/HDL-C ratio was independently positively correlated with the risk of NAFLD. Interaction tests suggested that the effect of RC/HDL-C ratio on NAFLD was significantly affected by sex. Additionally, receiver operating characteristic curve analysis showed that the area under the curve of RC/HDL-C ratio for identifying NAFLD was 0.82, which was significantly higher than that of other conventional lipid parameters. CONCLUSIONS:This study indicates for the first time that the higher RC/HDL-C ratio in the general population may be closely related to the increased risk of NAFLD.
10.1186/s12876-022-02216-x
The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and prevalence of periodontitis among US adults: a cross-sectional NHANES study.
Scientific reports
The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a recently developed lipid parameter, but there is currently a lack of research exploring its relationship with periodontitis. This study aims to identify the potential association between NHHR and periodontitis. The association between NHHR and periodontitis were examined through univariate and multivariate weighted logistic regression utilizing the National Health and Nutrition Examination Survey data from 2009 to 2014. The participants were grouped based on the type of periodontitis. This study included a total of 9023 participants, with 1947 individuals having no periodontitis, and an additional 7076 individuals suffering from periodontitis. Patients in periodontitis group demonstrated a statistically significant elevation in NHHR values 2.82 (2.05-3.80) compared to those in no periodontitis group (p < 0.001). Logistic regression analysis of variables demonstrated a positive association between NHHR and periodontitis [1.07 (1.02, 1.12) p = 0.0067]. The study revealed a positive association between NHHR and an elevated prevalence of periodontitis development. For each unit increase in NHHR, there is a 7% increase in the prevalence of periodontitis. Further investigations into NHHR may enhance our understanding of preventing and treating periodontitis. However, additional studies are required to validate these findings.
10.1038/s41598-024-56276-y
Carotid Atherosclerotic Plaque Features in Patients with Acute Ischemic Stroke.
Sun Runming,Wang Lixia,Guan Cuiling,Cao Wenyuan,Tian Bing
World neurosurgery
OBJECTIVE:To investigate the carotid atherosclerotic plaque features in patients with acute ischemic stroke. METHODS:A total of 288 patients meeting the included criteria were enrolled and divided into an ulcerated plaque group (n = 139) and a nonulcerated plaque group (n = 149). Patients in the ulcerated plaque group were further subdivided into <50% and ≥50% stenosis groups. Carotid plaque component characteristics including luminal stenosis, carotid plaque volume, hypoechoic plaque volume, and hyperechoic plaque volume were analyzed by color Doppler ultrasound measurement. Associations between ulcerated plaque and carotid plaque features were also evaluated. The relationships among the levels of MMP-9, hs-CRP, and carotid stenosis rate were detected by enzyme-linked immunosorbent assay. RESULTS:The plaque volume, hypoechoic plaque volume, and luminal stenosis in the ulcerated plaque group were higher than that of the nonulcerated plaque group (P < 0.05). Ulcerated plaque was positively associated with luminal stenosis, plaque volume, and hypoechoic plaque volume after adjusting for sex and age. The result remained similar after adjusting for age, sex, and carotid luminal stenosis. The levels of MMP-9 and hs-CRP in the ulcerated plaque group were significantly higher than those of the nonulcerated plaque group (P < 0.01). For the ulcerated plaque group, the higher the carotid stenosis rate, the higher the level of MMP-9 and hs-CRP. CONCLUSIONS:Higher carotid atherosclerosis plaque volume, hypoechoic plaque volume, and luminal carotid stenosis may be symptoms of ulcerated plaque. Increased MMP-9 and hs-CRP levels could be used as adjunctive therapies of carotid stenosis at the molecular level.
10.1016/j.wneu.2018.01.026
White matter hyperintensity determines ischemic stroke severity in symptomatic carotid artery stenosis.
Song Joomee,Kim Keon-Ha,Jeon Pyoung,Kim Young-Wook,Kim Dong-Ik,Park Yang-Jin,Park Moo-Seok,Chung Jong-Won,Seo Woo-Keun,Bang Oh Young,Ay Hakan,Kim Gyeong-Moon
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
INTRODUCTION:The aim of this study is to investigate the influence of white matter hyperintensity (WMH) on stroke severity and prognosis in patients with symptomatic carotid artery stenosis. METHODS:Patients with symptomatic carotid artery stenosis were retrieved from the Samsung Medical Center stroke registry from January 2011 to December 2016. Stroke severity was categorized into three levels according to National Institutes of Health Stroke Scale (NIHSS): transient ischemic attack (TIA) or transient symptoms with infarction (TSI), mild stroke, and moderate to severe stroke. WMH volume was measured with medical image processing and visualization. The clinical outcome was assessed using the modified Rankin scale on the 90th day from which the latest onset of the neurological symptom. Logistic regression was used to predict stroke severity, and ordinal regression was used to compare the clinical outcome. RESULTS:Among 158 patients, the numbers of patients with TIA or TSI, mild stroke, and moderate to severe stroke were 48 (30.4%), 59 (37.3%), and 51 (32.3%), respectively. The larger WMH volume was associated with moderate to severe strokes (TIA/TSI vs. moderate to severe strokes, odds ratio (OR) 2.318, 95% confidence interval (CI) 1.194-4.502, p = 0.007; mild vs. moderate to severe strokes, OR 1.972, 95% CI 1.118-3.479, p = 0.013). Patients with larger volume of WMH showed poorer clinical outcome (cutoff value: 9.71 cm, OR 2.099, 95% CI 1.030-4.311, p = 0.042). CONCLUSION:Our study showed that larger WMH volume is associated with more severe stroke and poorer prognosis in patients with symptomatic carotid artery stenosis.
10.1007/s10072-020-04958-6
Impact of carotid atherosclerosis in CHA2DS2-VASc-based risk score on predicting ischemic stroke in patients with atrial fibrillation.
Cho Dong-Hyuk,Choi Jong-Il,Choi Jimi,Kim Yun Gi,Oh Suk-Kyu,Kook Hyungdon,Lee Kwang No,Shim Jaemin,Park Seong-Mi,Shim Wan Joo,Kim Young-Hoon
The Korean journal of internal medicine
BACKGROUND/AIMS:Vascular disease is an established risk factor for stroke in patients with atrial fibrillation (AF), which is included in CHA2DS2-VASc score. However, the role of carotid atherosclerosis remains to be determined. METHODS:Three hundred-ten patients with AF who underwent carotid sonography were enrolled. RESULTS:During a median follow-up of 31 months, 18 events (5.8%) of stroke were identified. Patients with stroke had higher carotid intima-media thickness (CIMT) (1.16 ± 0.33 mm vs. 0.98 ± 0.25 mm, p = 0.017). CIMT was significantly increased according to the CHA2DS2-VASc score (p < 0.001) and it was correlated with left ventricular mass index and early diastolic mitral annular velocity (e'), a ratio of early transmitral flow velocity to e' (E/e') and pulmonary artery systolic pressure (all p < 0.05). Cox regression using multivariate models showed that carotid plaque was associated with the risk of stroke (hazard ratio, 3.748; 95% confidence interval [CI], 1.107 to 12.688; p = 0.034). C-statistics increased from 0.648 (95% CI, 0.538 to 0.757) to 0.716 (95% CI, 0.628 to 0.804) in the CHA2DS2-VASc score model after the addition of CIMT and carotid plaque as a vascular component (p = 0.013). CONCLUSION:Increased CIMT and presence of carotid plaque are associated with a high risk of ischemic stroke, and CIMT is related to myocardial remodeling and diastolic dysfunction, suggesting that carotid atherosclerosis can improve risk prediction of stroke in patients with AF, when included under vascular disease in the CHA2DS2-VASc scoring system.
10.3904/kjim.2019.099
Chronic Kidney Disease and Carotid Atherosclerosis in Patients With Acute Stroke.
Yu Fang-Ping,Zhao Ying-Chun,Gu Bin,Hu Jun,Yang Yong-Yi
The neurologist
BACKGROUND AND PURPOSE:Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for cardiovascular disease and stroke. Our aim was to examine the association between estimated glomerular filtration rate (eGFR) and carotid plaques, stenosis and occlusions, and to assess whether CKD and its severity affect carotid atherosclerosis in a cohort of unselected patients with acute stroke. METHODS:A total of 249 consecutive patients with acute stroke (ischemic or hemorrhagic) were included in this study and baseline eGFR, carotid intima-media thickness (cIMT), and carotid stenosis were evaluated. The eGFR was calculated using the modified Modification of Diet in Renal Disease equation, which was adjusted for data from Chinese CKD patients. An eGFR rate of <60 mL/min/1.73 m was defined as CKD. The cIMT and carotid plaques were detected by carotid ultrasound. RESULTS:CKD, defined as eGFR<60 mL/min/1.73 m, was found in 66 individuals (26.50%). Among the 5 subtypes, the level of low-density lipoprotein cholesterol was significantly higher in the moderate and severe stenosis groups compared with the normal, elevated cIMT and mild stenosis groups (P<0.01). The value of eGFR gradually decreased with increasing degree of carotid stenosis, and the differences between the groups were statistically significant (P<0.01). On linear regression analysis, eGFR was negatively correlated with the degree of carotid stenosis (r=0.03; P<0.05). On ordinal logistic regression analysis, eGFR was an independent risk factor associated with carotid atherosclerosis (1.05; 95% confidence interval, 0.47-1.63). CONCLUSIONS:There was a significant burden of atherosclerosis among individuals with CKD. CKD is an independent predictor of carotid plaques, stenoses, and occlusions in patients with acute stroke.
10.1097/NRL.0000000000000044
New indexes of body fat distribution, visceral adiposity index, body adiposity index, waist-to-height ratio, and metabolic disturbances in the obese.
Jabłonowska-Lietz Beata,Wrzosek Małgorzata,Włodarczyk Marta,Nowicka Grażyna
Kardiologia polska
BACKGROUND AND AIM:The aim of this study was to examine the relationship between new obesity-related indexes, anthropometric and biochemical parameters, and body composition in individuals with obesity. METHODS:The study group consisted of 72 women and 34 men, aged 39.0 ± 5.9 years, with a mean body mass index (BMI) of 32.6 ± 2.4 kg/m², admitted for body weight reduction. In all participants body weight (BW), height, waist circumference (WC), hip circumference (HC), BMI, waist-to-hip-ratio (WHR), visceral adiposity index (VAI), body adiposity index (BAI), and waist-to-height ratio (WHtR) were assessed. Using bioelectrical impedance (BIA, TANITA MC 180M) the following parameters were obtained: the level of visceral adipose tissue (VAT) and body fat percentage (FM%). Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), glucose, insulin, and insulin resistance (HOMA-IR) were determined. RESULTS:It was observed that almost all the studied indicators: WC, WHtR, BAI, VAI, and BMI, positively correlated with VAT estimated by bioimpedance, but only VAI, WC, and WHtR were strongly associated with glucose and lipid disturbances in the obese. BAI and BMI correlated with total FM%, while WC, WHtR, and VAI correlated with total body weight. CONCLUSIONS:The results indicate that VAI, WC, and WHtR can be useful in the assessment of increased VAT accumulation associated with disturbances in glucose and lipid metabolism. BAI should be calculated separately for each sex, then it could be also useful for the prediction of disturbances in glucose metabolism. However, further studies are needed to recognise cut-off values for BAI, as a marker of body fatness, associated with adverse health effects.
10.5603/KP.a2017.0149
The relationship between the visceral adiposity index and carotid atherosclerosis in different genders and age groups.
Saudi medical journal
OBJECTIVES:To investigate the possible relationship between visceral adiposity index (VAI) and carotid atherosclerosis(CAS) in different genders and age groups in China. METHODS:This study was an observational cross-sectional study and included 1996 participants who were health examination . From January 2018 to June 2019, people over 18 years old who had physical examinations were included in the study. Each participant completed a standard questionnaire, anthropometric measurements, ultrasonic examination, and provided blood samples for biochemical measurements. Regression models were utilized to evaluate the relationship between VAI and the CAS risk. An receiver operating characteristic (ROC) was utilized to predict VAI diagnostic efficacy for CAS. RESULTS:Adjusting for potential confounding factors, the risk of CAS increases as the level of VAI increases, and the odds ratio (OR) of the upper tertile is 3.09 (95% confidence interval [CI]:1.64-5.82, <0.001) in female >44 years of age. In females aged >44 years, the AUC of the VAI (AUC=0.610, 95%CI: 0.57-0.65) was higher than body mass index, WC, and HC (AUC=0.538 [95%CI:0.49-0.58], 0.499 [95%CI:0.45-0.54], and 0.526 [95%CI:0.48-0.57], VAI demonstrated a better ability to predict CAS (in females >44 years of age). However, this correlation was not observed in males. CONCLUSION:The relationship between VAI and CAS, with gender and age differences. Visceral adiposity index could be selected as new and simple predictors of CAS for females (>44 years of age) in China.
10.15537/smj.2022.43.2.20210824
A nonlinear correlation between the serum uric acid to creatinine ratio and the prevalence of hypertension: a large cross-sectional population-based study.
Renal failure
OBJECTIVE:To explore the relationship between the serum uric acid to creatinine (UA/Cr) ratio and the prevalence of hypertension. METHODS:In this cross-sectional study, we included 8571 individuals from the China Health and Nutrition Survey. Logistic regression analysis and restricted cubic spline (RCS) were used to analyze the relationship between the UA/Cr ratio and hypertension. RESULTS:Compared with individuals without hypertension, individuals with hypertension had higher UA/Cr ratios. Multivariate logistic regression analysis showed that a higher UA/Cr ratio was closely related to a higher risk of hypertension (as a continuous variable, OR: 1.054, 95% CI: 1.014-1.095, = 0.007; as a categorical variable, Q3 vs. Q1, OR: 1.183, 95% CI: 1.011-1.384, = 0.035; Q4 vs. Q1, OR: 1.347, 95% CI: 1.146-1.582, < 0.001). Subgroup analysis revealed that the correlation between the UA/Cr ratio and hypertension risk was stable in all subgroups except for the subgroup with diabetes and the subgroup with a BMI ≥ 28 kg/m ( < 0.05). Sensitivity analysis confirmed the robustness of the relationship between a higher UA/Cr ratio and a higher risk of hypertension ( < 0.05). The RCS showed that the UA/Cr ratio was nonlinearly related to hypertension risk. Further threshold effect showed that only a UA/Cr ratio less than 5.0 was related to hypertension risk (OR: 1.178, 95% CI: 1.086-1.278, < 0.001), and the 2-piecewise linear regression model was superior to the 1-line linear regression model ( < 0.05). CONCLUSION:The UA/Cr ratio was associated with the prevalence of hypertension.
10.1080/0886022X.2023.2296002
Blood Cell Count Indexes of Systemic Inflammation in Carotid Artery Disease: Current Evidence and Future Perspectives.
Dettori Paola,Paliogiannis Panagiotis,Pascale Rosa M,Zinellu Angelo,Mangoni Arduino A,Pintus Gianfranco
Current pharmaceutical design
Carotid artery disease is commonly encountered in clinical practice and accounts for approximately 30% of ischemic strokes in the general population. Numerous biomarkers have been investigated as predictors of the onset and progression of carotid disease, the occurrence of cerebrovascular complications, and overall prognosis. Among them, blood cell count (BCC) indexes of systemic inflammation might be particularly useful, from a pathophysiological and clinical point of view, given the inflammatory nature of the atherosclerotic process. The aim of this review is to discuss the available evidence regarding the role of common BCC indexes, such as the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW), in the diagnosis and risk stratification of carotid artery disease, and their potential clinical applications.
10.2174/1381612826666201222155630
Red blood cell distribution width is associated with increased interactions of blood cells with vascular wall.
Scientific reports
The mechanism underlying the association between elevated red cell distribution width (RDW) and poor prognosis in variety of diseases is unknown although many researchers consider RDW a marker of inflammation. We hypothesized that RDW directly affects intravascular hemodynamics, interactions between circulating cells and vessel wall, inducing local changes predisposing to atherothrombosis. We applied different human and animal models to verify our hypothesis. Carotid plaques harvested from patients with high RDW had increased expression of genes and proteins associated with accelerated atherosclerosis as compared to subjects with low RDW. In microfluidic channels samples of blood from high RDW subjects showed flow pattern facilitating direct interaction with vessel wall. Flow pattern was also dependent on RDW value in mouse carotid arteries analyzed with Magnetic Resonance Imaging. In different mouse models of elevated RDW accelerated development of atherosclerotic lesions in aortas was observed. Therefore, comprehensive biological, fluid physics and optics studies showed that variation of red blood cells size measured by RDW results in increased interactions between vascular wall and circulating morphotic elements which contribute to vascular pathology.
10.1038/s41598-022-17847-z
A Correlational Study on Cerebral Microbleeds and Carotid Atherosclerosis in Patients with Ischemic Stroke.
Zhao Fang-Fang,Gao Hao-Yuan,Gao Yuan,Zhao Zhuan,Li Juan,Ning Fang-Bo,Zhang Xin-Na,Wang Zhi-Gao,Yu Ai-Ling,Guo Yan-Yong,Sun Bao-Liang
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
PURPOSE:This study aimed to investigate the correlation between cerebral microbleeds and carotid atherosclerosis in patients with ischemic stroke. SUBJECTS AND METHODS:Patients with ischemic stroke treated in a hospital in China from 2016 to 2017 were enrolled in the study. Based on the results from susceptibility-weighted imaging, the patients were divided into cerebral microbleed and noncerebral microbleed groups. The degree of carotid atherosclerosis was assessed with carotid intima-media thickness (CIMB) and Crouse score of carotid plaque. The details of patients' demographic information, cerebrovascular disease-related risk factors, carotid atherosclerosis indices, cerebral microbleed distribution, and grading were recorded, compared, and analyzed. RESULTS:Logistic regression analysis of the 198 patients showed that CIMB and Crouse score were significantly correlated with the occurrence of cerebral microbleeds. The CIMB thickening group (P = .03) and the plaque group (P = .01) were more susceptible to cerebral microbleeds. In the distribution of cerebral microbleed sites, Crouse scores were the highest in the mixed group and showed a statistically significant difference (P < .01). As the degree of carotid atherosclerosis increased, the average number of cerebral microbleeds also increased (P < .01). The receiver operating characteristic curve analysis of the carotid atherosclerosis indices showed a statistically significant difference. The CIMB value combined with the Crouse score was the best indicator (P < .01). CONCLUSION:In patients with ischemic stroke, cerebral microbleeds are closely related to carotid atherosclerosis. Active control of carotid atherosclerosis is important to prevent cerebral microbleeds in patients with ischemic stroke.
10.1016/j.jstrokecerebrovasdis.2018.04.009
Red cell distribution width and carotid atherosclerosis progression. The Tromsø Study.
Lappegård Jostein,Ellingsen Trygve S,Vik Anders,Skjelbakken Tove,Brox Jan,Mathiesen Ellisiv B,Johnsen Stein Harald,Brækkan Sigrid K,Hansen John-Bjarne
Thrombosis and haemostasis
Red cell distribution width (RDW), a measure of the size variability of circulating erythrocytes, is associated with cardiovascular morbidity and mortality. We aimed to investigate whether RDW was associated with progression of atherosclerotic plaques in subjects recruited from the general population. Baseline characteristics, including RDW, were collected from 4677 participants in the fourth survey of the Tromsø Study conducted in 1994/95. Prevalence of carotid plaques and total plaque area (TPA) were assessed by ultrasonographic imaging at baseline and after seven years of follow-up. Generalised linear models were used to analyse change in TPA across tertiles of RDW. Change in TPA was significantly higher across tertiles of RDW in crude analysis and in multivariable analysis adjusted for cardiovascular risk factors. The mean change in TPA increased from 5.6 mm² (4.9-6.4) in tertile 1 (RDW ≤ 12.6 %) to 6.7 mm² (5.9-7.6) in tertile 3 (RDW ≥ 13.3) in multivariable analysis adjusted for body mass index, total cholesterol, HDL cholesterol, systolic blood pressure, self-reported diabetes, smoking status, platelet count, white blood cell count, and hs-CRP levels (p for trend 0.003). A 1 % increase in RDW was associated with 0.6 mm² (0.1-1.2) increase in TPA in multivariable analysis (p=0.03). RDW was associated with progression of atherosclerosis after adjustments for traditional atherosclerotic risk factors. Our findings suggest that the link between RDW and cardiovascular morbidity and mortality may be explained by atherosclerosis.
10.1160/TH14-07-0606
Carotid Intima-Media Thickness is Not Associated with Markers of Atherosclerosis in Stroke Patients.
García García Jorge,Roquer Jaume,Serena Joaquín,Castillo José,Blanco Miguel,Díaz-Maroto Inmaculada,Segura Tomás,
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:It has been argued that carotid intima-media thickness (IMT) could better reflect an adaptive response of the vessel wall rather than being a marker of atherosclerosis. We explore this hypothesis by analyzing the ARTICO data. METHODS:The ARTICO study was designed to evaluate the prognostic value of the pathological ankle-brachial index (ABI) for the emergence of new vascular events in patients who have suffered a noncardioembolic stroke. Collected variables were as follows: vascular risk factors, mean waist perimeter, quantification of carotid IMT, characteristics of carotid plaques, ABI, and presence of microalbuminuria. RESULTS:A total of 591 patients with a complete carotid evaluation were available. There was no correlation between ABI and IMT (Spearman's, p NS). Logistic regression revealed that pathological ABI correlated significantly only with internal carotid artery stenosis greater than or equal to 50% (OR [odds ratio] 2.80, 1.66-4.71, P < .01) and peripheral artery disease (OR 3.33, 1.63-6.78, P < .01). However, multivariate regression analysis demonstrated that carotid IMT was independently associated with age (OR 1.05, 95% confidence interval [CI] 1.02-1.09, P < .01), hypertension (OR 1.83, 95% CI 1.02-3.26, P = .04), waist circumference (OR 1.03, 95% CI 1.01-1.05, P < .01), and microalbuminuria (OR 2.02, 95% CI 1.22-3.35, P < .01). CONCLUSION:In our patients, carotid IMT does not seem to be associated with unequivocal markers of atheromatosis such as the existence of relevant carotid plaques or pathological ABI. These results as well as the association of IMT with age, hypertension, microalbuminuria, and mean waist perimeter support the hypothesis that IMT must be considered a risk factor for general vascular disease rather than a marker of atherosclerotic burden.
10.1016/j.jstrokecerebrovasdis.2016.01.002
Association of Platelet to lymphocyte ratio with non-culprit atherosclerotic plaque vulnerability in patients with acute coronary syndrome: an optical coherence tomography study.
Wang Xuedong,Xie Zulong,Liu Xinxin,Huang Xingtao,Lin Jiale,Huang Dan,Yu Bo,Hou Jingbo
BMC cardiovascular disorders
BACKGROUND:The platelet to lymphocyte ratio (PLR), an indirect inflammatory biomarker, has been recently demonstrated to be associated with severity of coronary artery disease. In the present study, we sought to investigate whether PLR is associated with vulnerable plaque characteristics of non-culprit lesions in patients with acute coronary syndrome (ACS). METHODS:The patients in our study were divided into two groups (high PLR group and low PLR group). A total of 119 non-culprit plaques from 71 patients with ACS were assessed by optical coherence tomography (OCT). RESULTS:The non-culprit plaques in high PLR group exhibited thinner fibrous cap thickness (FCT) (88.60 ± 44.70 vs. 119.28 ± 50.22 μm, P = 0.001), greater maximum lipid arc (271.73 ± 71.66 vs. 240.60 ± 76.69°, P = 0.027) and increased incidence of thin-cap fibroatheroma (TCFA) (34.0% vs. 15.9%, P = 0.022) compared with those in low PLR group. Meanwhile, PLR was negatively associated with FCT (r = -0.329, P < 0.001). Furthermore, multivariate regression analysis showed that PLR [OR: 1.023 (95% CI: 1.005-1.041), P = 0.012] and LDL-C [OR: 1.892 (95% CI: 1.106-3.239), P = 0.020] were significant predictors of TCFA. CONCLUSIONS:High level of PLR may be associated with vulnerable plaque features of non-culprit lesions in patients with ACS. PLR, a cheap and easily available index, may surve as a useful inflammatory marker in reflecting plaque vulnerability.
10.1186/s12872-017-0618-y
Development and validation of a nomogram model for prediction of stroke-associated pneumonia associated with intracerebral hemorrhage.
BMC geriatrics
BACKGROUND:We aimed to establish risk factors for stroke-associated pneumonia (SAP) following intracerebral hemorrhage (ICH) and develop an efficient and convenient model to predict SAP in patients with ICH. METHODS:Our study involved 1333 patients consecutively diagnosed with ICH and admitted to the Neurology Department of the First Affiliated Hospital of Wenzhou Medical University. The 1333 patients were randomly divided (3:1) into the derivation cohort (n = 1000) and validation Cohort (n = 333). Variables were screened from demographics, lifestyle-related factors, comorbidities, clinical symptoms, neuroimaging features, and laboratory tests. In the derivation cohort, we developed a prediction model with multivariable logistic regression analysis. In the validation cohort, we assessed the model performance and compared it to previously reported models. The area under the receiver operating characteristic curve (AUROC), GiViTI calibration belt, net reclassification index (NRI), integrated discrimination index (IDI) and decision curve analysis (DCA) were used to assess the prediction ability and the clinical decision-making ability. RESULTS:The incidence of SAP was 19.9% and 19.8% in the derivation (n = 1000) and validation (n = 333) cohorts, respectively. We developed a nomogram prediction model including age (Odds Ratio [OR] 1.037, 95% confidence interval [CI] 1.020-1.054), male sex (OR 1.824, 95% CI 1.206-2.757), multilobar involvement (OR 1.851, 95% CI 1.160-2.954), extension into ventricles (OR 2.164, 95% CI 1.456-3.215), dysphagia (OR 3.626, 95% CI 2.297-5.725), disturbance of consciousness (OR 2.113, 95% CI 1.327-3.362) and total muscle strength of the worse side (OR 0.93, 95% CI 0.876-0.987). Compared with previous models, our model was well calibrated and showed significantly higher AUROC, better reclassification ability (improved NRI and IDI) and a positive net benefit for predicted probability thresholds between 10% and 73% in DCA. CONCLUSIONS:We developed a simple, valid, and clinically useful model to predict SAP following ICH, with better predictive performance than previous models. It might be a promising tool to assess the individual risk of developing SAP for patients with ICH and optimize decision-making.
10.1186/s12877-023-04310-5
Fibrinogen-to-Albumin Ratio and Clinical Outcomes in Patients With Large Artery Atherosclerosis Stroke.
Journal of the American Heart Association
BACKGROUND:A high fibrinogen-to-albumin ratio (FAR), a novel inflammatory marker, is considered to be a prognostic marker in vascular diseases. However, the association of FAR with large artery atherosclerosis (LAA) stroke is still unknown. This study was conducted to evaluate the association between FAR levels and clinical outcomes in patients with acute LAA stroke. METHODS AND RESULTS:A total of 809 patients within 72 hours of LAA stroke were included and followed up to 1 year. FAR was calculated as fibrinogen (g/L)/albumin (g/L). The associations of FAR with clinical outcomes were assessed by multivariate Cox regression or logistic regression analysis. Clinical outcomes included stroke recurrence, all-cause death, poor functional outcome (modified Rankin Scale score 3-6), and dependence (modified Rankin Scale score 3-5). Among the 809 patients with acute LAA stroke, the median FAR was 0.075 (interquartile range, 0.064-0.087). At 1 year, 103 (12.7%) patients had stroke recurrence, 105 (13.0%) had poor functional outcome, 76 (9.8%) had dependence, and 29 (3.6%) had died. After adjusting for all confounding risk factors, a high FAR level was associated with stroke recurrence (hazard ratio, 2.57 [95% CI, 1.32-5.02]), poor functional outcome (odds ratio, 3.30 [95% CI, 1.57-6.94]), and dependence (odds ratio, 3.49 [95% CI, 1.49-8.19]). CONCLUSIONS:A high FAR level was associated with an increased risk of stroke recurrence, poor functional outcome, and dependence in patients with acute LAA stroke.
10.1161/JAHA.123.030837
The age-dependent immune response to ischemic stroke.
Current opinion in neurobiology
Stroke is a devastating cause of global morbidity and mortality. Ischemic brain injury triggers a profound local and systemic immune response that participates in stroke pathophysiology. In turn, this immune response has emerged as a potential therapeutic target. In order to maximize its therapeutic potential, it is critical to understand how the immune response to ischemic brain injury is affected by age - the strongest non-modifiable risk factor for stroke. The development of multi-omics and single-cell technologies has provided a more comprehensive characterization of transcriptional and cellular changes that occur during aging. In this review, we summarize recent advances in our understanding of how age-related immune alterations shape differential stroke outcomes in older versus younger organisms, highlighting studies in both experimental mouse models and patient cohorts. Wherever possible, we emphasize outstanding questions that present important avenues for future investigation with therapeutic value for the aging population.
10.1016/j.conb.2022.102670
Memantine Protects From Exacerbation of Ischemic Stroke and Blood Brain Barrier Disruption in Mild But Not Severe Hyperhomocysteinemia.
Gu Sean X,Sonkar Vijay K,Katare Parmeshwar B,Kumar Rahul,Kruger Warren D,Arning Erland,Bottiglieri Teodoro,Lentz Steven R,Dayal Sanjana
Journal of the American Heart Association
Background Hyperhomocysteinemia is a risk factor for ischemic stroke; however, a targeted treatment strategy is lacking partly because of limited understanding of the causal role of homocysteine in cerebrovascular pathogenesis. Methods and Results In a genetic model of cystathionine beta synthase (CBS) deficiency, we tested the hypothesis that elevation in plasma total homocysteine exacerbates cerebrovascular injury and that memantine, a N-methyl-D-aspartate receptor antagonist, is protective. Mild or severe elevation in plasma total homocysteine was observed in (6.1±0.3 μmol/L) or (309±18 μmol/L) mice versus (3.1±0.6 μmol/L) mice. Surprisingly, and mice exhibited similar increases in cerebral infarct size following middle cerebral artery ischemia/reperfusion injury, despite the much higher total homocysteine levels in mice. Likewise, disruption of the blood brain barrier was observed in both and mice. Administration of the N-methyl-D-aspartate receptor antagonist memantine protected but not mice from cerebral infarction and blood brain barrier disruption. Our data suggest that the differential effect of memantine in versus mice may be related to changes in expression of N-methyl-D-aspartate receptor subunits. , but not mice had increased expression of NR2B subunit, which is known to be relatively insensitive to homocysteine. Conclusions These data provide experimental evidence that even a mild increase in plasma total homocysteine can exacerbate cerebrovascular injury and suggest that N-methyl-D-aspartate receptor antagonism may represent a strategy to prevent reperfusion injury after acute ischemic stroke in patients with mild hyperhomocysteinemia.
10.1161/JAHA.119.013368
Joint High Level of Oxidized Low-Density Lipoprotein and High-Sensitivity C-Reactive Protein are Associated With Recurrent Stroke and Poor Functional Outcome in Minor Stroke or Transient Ischemic Attack.
Journal of the American Heart Association
Background Oxidized low-density lipoprotein (oxLDL) and hs-CRP (high-sensitivity C-reactive protein) plays an important role in cardiovascular diseases though inflammation and oxidative stress, etc. However, evidence on their combined effects on stroke prognosis is still limited. We aimed to explore the joint association of oxLDL and hs-CRP with outcomes of minor stroke or transient ischemic attack. Methods and Results A subgroup of 3019 patients from the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Baseline oxLDL and hs-CRP levels were measured. The primary outcome was any stroke within 90 days. The secondary outcomes included any stroke within 1 year, and ischemic stroke, combined vascular events, and poor functional outcomes (modified Rankin Scale 2-6 or 3-6) at 90 days and 1 year. Vascular events outcomes were analyzed with Cox proportional hazards and poor functional outcomes with logistic models. Elevated oxLDL (>28.81 μg/dL) and hs-CRP (>4.20 mg/L) was observed in 624 (20.67%) of the 3019 patients. Patients with oxLDL >28.81 μg/dL and hs-CRP >4.20 mg/L had a higher risk of recurrent stroke within 90 days (adjusted hazard ratio, 1.52; 95% CI, 1.17-1.97), compared with those with oxLDL ≤28.81 μg/dL and hs-CRP ≤4.20 mg/L, after adjusting relevant confounding factors (=0.002). Similar results were observed for secondary outcomes (<0.05 for all). Conclusions In patients with minor stroke or transient ischemic attack, joint high levels of oxLDL and hs-CRP was associated with increased risk of recurrent stroke, combined vascular events, and poor functional outcome.
10.1161/JAHA.122.027665
Creatine Kinase Is Associated With Recurrent Stroke and Functional Outcomes of Ischemic Stroke or Transient Ischemic Attack.
Journal of the American Heart Association
Background Many patients after stroke are found to have elevated serum creatine kinase (CK). This study aimed to investigate the associations between serum CK levels and clinical outcomes in patients with acute ischemic stroke or transient ischemic attack. Methods and Results The study included 8910 patients with acute ischemic stroke or transient ischemic attack from the CNSR-III (Third China National Stroke Registry). Baseline serum CK levels after admission were measured. The associations between CK and clinical outcomes (stroke recurrence, death, and disability, defined as modified Rankin scale score 3-6 or 2-6) were analyzed. Patients with elevated CK levels had higher risks of recurrent stroke (hazard ratio [HR], 1.53; 95% CI, 1.21-1.93), death (HR, 1.68; 95% CI, 1.10-2.58), and disability (modified Rankin scale score, 3-6; odds ratio, 1.57; 95% CI, 1.29-1.90) at 3 months after adjusting confounding factors. Similar results were found at 1 year. The effects of CK on death and disability were more significant in male patients than female patients ( value for interaction <0.05). Elevated CK-MB levels were not associated with clinical outcomes in this study. Conclusions Elevated serum CK after ischemic stroke or transient ischemic attack is associated with higher risks of recurrent stroke, death, and disability at 3 months and 1 year. Serum CK may act as a useful predictor for recurrent stroke and poor functional outcomes in patients with acute ischemic stroke or transient ischemic attack. Sex modifies the relationship between elevated CK and disability or death.
10.1161/JAHA.121.022279
Association Between Carotid Artery Perivascular Fat Density and Cerebrovascular Ischemic Events.
Baradaran Hediyeh,Myneni Pavan K,Patel Praneil,Askin Gulce,Gialdini Gino,Al-Dasuqi Khalid,Kamel Hooman,Gupta Ajay
Journal of the American Heart Association
Background Studies have shown that pericoronary artery inflammation can be accurately detected via increased attenuation on computed tomography. Our purpose was to evaluate the association between pericarotid inflammation, measured by density of carotid perivascular fat on computed tomography angiography, with stroke and transient ischemic attack. Methods and Results We screened computed tomography angiography examinations for patients with unilateral internal carotid artery ( ICA ) stenosis ≥50% to 99%. A blinded neuroradiologist placed regions-of-interest in the pericarotid fat on the slice showing maximal stenosis. Two-sample t tests were performed to assess between-subject differences in mean Hounsfield Units in carotid perivascular fat between symptomatic and asymptomatic patients. Paired t tests were used to assess within-subject differences in mean Hounsfield Units between stenotic versus nonstenotic ICA s in a given patient. We included 94 patients, including 42 symptomatic and 52 asymptomatic patients. In the between-subject analysis of stenotic ICA s, we found symptomatic patients had higher mean pericarotid fat density compared with asymptomatic patients (-66.2±19.2 versus -77.1±20.4, P=0.009). When comparing nonstenotic ICA s, there was no significant difference between pericarotid fat density in symptomatic compared with asymptomatic patients (-81.0±13.3 versus -85.3±18.0: P=0.198). Within-subject comparison showed statistically significant increased density in stenotic ICA versus nonstenotic ICA with mean Hounsfield Units difference of 11.1 ( P<0.0001). Conclusions We found increased density, a surrogate marker for perivascular inflammation, in the fat surrounding ICA s ipsilateral to stroke or transient ischemic attack compared with asymptomatic ICA s. Our findings suggest that inflammation associated with culprit carotid plaques extends beyond the vessel lumen and can be identified using simple methods on computed tomography angiography imaging.
10.1161/JAHA.118.010383
Independent Relevance of Different Measures of Adiposity for Carotid Intima-Media Thickness in 40 000 Adults in UK Biobank.
Journal of the American Heart Association
Background Uncertainty persists about carotid intima-media thickness (CIMT) as a marker of subclinical atherosclerosis and the independent relevance of different measures of adiposity for CIMT. We assessed the independent relevance of general adiposity (body mass index), central adiposity (waist circumference), and body composition (fat mass index and fat-free mass index) with CIMT among adults in the United Kingdom. Methods and Results Multivariable linear regression of cross-sectional analyses of UK Biobank assessed the mean percentage difference in CIMT associated with equivalent differences in adiposity measures. To assess independent associations, body mass index and waist circumference were mutually adjusted, as were fat mass index and fat-free mass index. Among 39 367 participants (mean [SD] age 64 [8] years, 52% female, 97% White), median (interquartile range) CIMT was 0.65 (0.14) mm in women and 0.69 (0.18) mm in men. All adiposity measures were linearly and positively associated with CIMT after adjusting for confounders. Fat-free mass index was most strongly associated with CIMT after adjustment for fat mass index (% difference in CIMT: 1.23 [95% CI 0.93-1.53] women; 3.44 [3.01-3.86] men), while associations of fat mass index were attenuated after adjustment for fat-free mass index (0.28 [-0.02, 0.58] women; -0.59 [-0.99, -0.18] men). After mutual adjustment, body mass index remained positively associated with CIMT, but waist circumference was completely attenuated. Conclusions Fat-free mass index was the adiposity measure most strongly associated with CIMT, suggesting that CIMT may reflect vascular compensatory remodeling rather than atherosclerosis. Hence, screening for subclinical atherosclerosis should evaluate carotid plaques in addition to CIMT.
10.1161/JAHA.122.026694
Symptomatic Carotid Plaques Demonstrate Less Leaky Plaque Microvasculature Compared With the Contralateral Side: A Dynamic Contrast-Enhanced Magnetic Resonance Imaging Study.
Crombag Geneviève A J C,van Hoof Raf H M,Holtackers Robert J,Schreuder Floris H B M,Truijman Martine T B,Schreuder Tobien A H C M L,van Orshoven Narender P,Mess Werner H,Hofman Paul A M,van Oostenbrugge Robert J,Wildberger Joachim E,Kooi M Eline
Journal of the American Heart Association
Background Rupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque. The objective of the present study is to investigate whether there is a difference in plaque microvasculature (the volume transfer coefficient K) between the ipsilateral symptomatic and contralateral asymptomatic carotid plaque using noninvasive dynamic contrast-enhanced magnetic resonance imaging. Methods and Results Eighty-eight patients with recent transient ischemic attack or ischemic stroke and ipsilateral >2 mm carotid plaque underwent 3 T magnetic resonance imaging to identify plaque components and to determine characteristics of plaque microvasculature. The volume transfer coefficient K, indicative for microvascular density, flow, and permeability, was calculated for the ipsilateral and asymptomatic plaque, using a pharmacokinetic model (Patlak). Presence of a lipid-rich necrotic core, intraplaque hemorrhage, and a thin and/or ruptured fibrous cap was assessed on multisequence magnetic resonance imaging . We found significantly lower K in the symptomatic carotid plaque compared with the asymptomatic side (0.057±0.002 min versus 0.062±0.002 min; P=0.033). There was an increased number of slices with intraplaque hemorrhage (0.9±1.6 versus 0.3±0.8, P=0.002) and lipid-rich necrotic core (1.4±1.9 versus 0.8±1.4, P=0.016) and a higher prevalence of plaques with a thin and/or ruptured fibrous cap (32% versus 17%, P=0.023) at the symptomatic side. Conclusions K was significantly lower in symptomatic carotid plaques, indicative for a decrease of plaque microvasculature in symptomatic plaques. This could be related to a larger amount of necrotic tissue in symptomatic plaques. Clinical Trial Registration URL : http://www.clinicaltrials.gov.uk . Unique identifier: NCT 01208025.
10.1161/JAHA.118.011832
Expansive arterial remodeling of the carotid arteries and its effect on atherosclerotic plaque composition and vulnerability: an in-vivo black-blood 3T CMR study in symptomatic stroke patients.
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
BACKGROUND:Based on intravascular ultrasound of the coronary arteries expansive arterial remodeling is supposed to be a feature of the vulnerable atheroslerotic plaque. However, till now little is known regarding the clinical impact of expansive remodeling of carotid lesions. Therefore, we sought to evaluate the correlation of expansive arterial remodeling of the carotid arteries with atherosclerotic plaque composition and vulnerability using in-vivo Cardiovascular Magnetic Resonance (CMR). METHODS:One hundred eleven symptomatic patients (74 male/71.8 ± 10.3y) with acute unilateral ischemic stroke and carotid plaques of at least 2 mm thickness were included. All patients received a dedicated multi-sequence black-blood carotid CMR (3Tesla) of the proximal internal carotid arteries (ICA). Measurements of lumen, wall, outer wall, hemorrhage, calcification and necrotic core were determined. Each vessel-segment was classified according to American Heart Association (AHA) criteria for vulnerable plaque. A modified remodeling index (mRI) was established by dividing the average outer vessel area of the ICA segments by the lumen area measured on TOF images in a not affected reference segment at the distal ipsilateral ICA. Correlations of mRI and clinical symptoms as well as plaque morphology/vessel dimensions were evaluated. RESULTS:Seventy-eight percent (157/202) of all internal carotid arteries showed atherosclerotic disease with AHA Lesion-Type (LT) III or higher. The mRI of the ICA was significantly different in normal artery segments (AHA LT I; mRI 1.9) compared to atherosclerotic segments (AHA LT III-VII; mRI 2.5; p < 0.0001). Between AHA LT III-VII there was no significant difference of mRI. Significant correlations (p < 0.05) of the mRI with lumen-area (LA), wall-area (WA), vessel-area (VA) and wall-thickness (WT), necrotic-core area (NC), and ulcer-area were observed. With respect to clinical presentation (symptomatic/asymptomatic side) and luminal narrowing (stenotic/non-stenotic) no relevant correlations or significant differences regarding the mRI were found. CONCLUSION:Expansive arterial remodeling exists in the ICA. However, no significant association between expansive arterial remodeling, stroke symptoms, complicated AHA VI plaque, and luminal stenosis could be established. Hence, results of our study suggest that expansive arterial remodeling is not a very practical marker for plaque vulnerability in the carotid arteries.
10.1186/s12968-016-0229-2
Hypertriglyceridemic Waist: A Simple Marker of High-Risk Atherosclerosis Features Associated With Excess Visceral Adiposity/Ectopic Fat.
Journal of the American Heart Association
BACKGROUND:Subclinical atherosclerosis identification remains challenging; abdominal visceral adiposity may improve risk stratification beyond traditional cardiovascular risk factors. Hypertriglyceridemic waist, a visceral adiposity marker combining elevated triglycerides (≥2 mmol/L) and waist circumference (≥90 cm), has been related to carotid atherosclerosis, although associations with high-risk features, including lipid-rich necrotic core (LRNC), remain unknown. We tested the hypothesis that hypertriglyceridemic waist is an independent marker of high-risk atherosclerosis features. METHODS AND RESULTS:In this cross-sectional study including 467 white men (mean age, 45.9±14.8 years; range 19.4-77.6 years), carotid atherosclerosis characteristics were examined by magnetic resonance imaging and associations with hypertriglyceridemic waist and benefits beyond Framingham Risk Score (FRS) and Pathobiological Determinants of Atherosclerosis in Youth (PDAY) were determined. Subclinical carotid atherosclerosis was present in 61.9% of participants, whereas 50.1% had LRNC. Hypertriglyceridemic waist was associated with carotid maximum wall thickness (=0.014), wall volume (=0.025), normalized wall index (=0.004), and Carotid Atherosclerosis Score (derived from wall thickness and LRNC; =0.049). Hypertriglyceridemic waist was associated with carotid LRNC volume beyond FRS (=0.037) or PDAY (=0.015), contrary to waist circumference alone (both >0.05). Although 69.7% and 62.0% of participants with carotid atherosclerosis and/or LRNC were not high-risk by FRS or PDAY, respectively, hypertriglyceridemic waist correctly reclassified 9.7% and 4.5% of them, respectively. Combining hypertriglyceridemic waist with FRS (net reclassification improvement=0.17; <0.001) or PDAY (net reclassification improvement=0.05; =0.003) was superior to each score alone in identifying individuals with carotid atherosclerosis and/or LRNC. CONCLUSIONS:Hypertriglyceridemic waist is an independent marker of carotid high-risk atherosclerosis features in men, improving on FRS and PDAY risk score.
10.1161/JAHA.117.008139
A practical modification to a resting state fMRI protocol for improved characterization of cerebrovascular function.
Stickland Rachael C,Zvolanek Kristina M,Moia Stefano,Ayyagari Apoorva,Caballero-Gaudes César,Bright Molly G
NeuroImage
Cerebrovascular reactivity (CVR), defined here as the Blood Oxygenation Level Dependent (BOLD) response to a CO pressure change, is a useful metric of cerebrovascular function. Both the amplitude and the timing (hemodynamic lag) of the CVR response can bring insight into the nature of a cerebrovascular pathology and aid in understanding noise confounds when using functional Magnetic Resonance Imaging (fMRI) to study neural activity. This research assessed a practical modification to a typical resting-state fMRI protocol, to improve the characterization of cerebrovascular function. In 9 healthy subjects, we modelled CVR and lag in three resting-state data segments, and in data segments which added a 2-3 minute breathing task to the start of a resting-state segment. Two different breathing tasks were used to induce fluctuations in arterial CO pressure: a breath-hold task to induce hypercapnia (CO increase) and a cued deep breathing task to induce hypocapnia (CO decrease). Our analysis produced voxel-wise estimates of the amplitude (CVR) and timing (lag) of the BOLD-fMRI response to CO by systematically shifting the CO regressor in time to optimize the model fit. This optimization inherently increases gray matter CVR values and fit statistics. The inclusion of a simple breathing task, compared to a resting-state scan only, increases the number of voxels in the brain that have a significant relationship between CO and BOLD-fMRI signals, and improves our confidence in the plausibility of voxel-wise CVR and hemodynamic lag estimates. We demonstrate the clinical utility and feasibility of this protocol in an incidental finding of Moyamoya disease, and explore the possibilities and challenges of using this protocol in younger populations. This hybrid protocol has direct applications for CVR mapping in both research and clinical settings and wider applications for fMRI denoising and interpretation.
10.1016/j.neuroimage.2021.118306
Mapping Cerebrovascular Reactivity Impairment in Patients With Symptomatic Unilateral Carotid Artery Disease.
Sebök Martina,van Niftrik Christiaan Hendrik Bas,Winklhofer Sebastian,Wegener Susanne,Esposito Giuseppe,Stippich Christoph,Luft Andreas,Regli Luca,Fierstra Jorn
Journal of the American Heart Association
Background Comprehensive hemodynamic impairment mapping using blood oxygenation-level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease. Methods and Results This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age-matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion-weighted imaging. Sixty-seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole-brain and ipsilateral hemisphere mean BOLD-CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04, =0.004 and 0.09±0.09 versus 0.18±0.04, <0.001) and ICA stenosis cohort (0.12±0.08 versus 0.16±0.05, =0.01 and 0.09±0.09 versus 0.15±0.05, =0.01); however, only 40 (58%) patients of the cohort showed significant BOLD-CVR impairment. Conversely, there was no difference in mean BOLD-CVR values between healthy patients and patients with ICA stenosis, although 5 (14%) patients with ICA stenosis showed a significant BOLD-CVR impairment. No significant BOLD-CVR difference was discernible between patients with hemodynamic ischemic infarcts versus those with embolic infarct distribution (0.11±0.08 versus 0.13±0.06, =0.12). Conclusions Comprehensive BOLD-CVR mapping allows for identification of hemodynamically relevant symptomatic unilateral carotid artery stenosis or occlusion.
10.1161/JAHA.121.020792
Negative Carotid Artery Remodeling in Early Type 2 Diabetes Mellitus and Increased Carotid Plaque Vulnerability in Obesity as Assessed by Magnetic Resonance Imaging.
Journal of the American Heart Association
Background Ischemic stroke from carotid plaque embolism remains a major cause of morbidity in patients with type 2 diabetes mellitus (T2 DM ). However, the effect of early T2 DM and obesity on carotid remodeling and plaque burden remains elusive. We assessed carotid remodeling and plaque composition by carotid magnetic resonance imaging in patients with short-duration T2 DM compared with a sex- and age-matched control group. Methods and Results One hundred patients with T2 DM (duration <5 years) and 100 sex- and age-matched controls underwent bilateral carotid artery magnetic resonance imaging in a 1.5-T magnetic resonance imaging scanner. Plaque burden was quantified by normalized wall index, maximum wall thickness, maximum wall area, and minimum lumen size. Plaque morphology was quantified by calcified plaque volume, necrotic core volume, and loose matrix volume. Magnetic resonance imaging data were available for 149 and 177 carotid arteries from T2 DM patients and controls, respectively. Adjusted for age and sex, T2 DM was associated with increased plaque burden indicated by a higher normalized wall index (ratio 1.03 [95% confidence interval, 1.002; 1.06], P=0.03), and negative remodeling indicated by a lower minimum lumen area (ratio 0.81 [0.74; 0.89], P<0.001), and lower maximum wall area (ratio 0.94 [0.88; 1.00], P=0.048) compared with controls. In both T2 DM and controls, body mass index ≥30.0 kg/m was associated with an 80% increase in total calcified plaque volume, and a 44% increase in necrotic core volume compared with body mass index <25.0 kg/m. Conclusions Short-duration T2 DM was associated with increased carotid plaque burden and negative remodeling. Obesity was associated with increased carotid artery necrotic core volume and calcification independently of diabetes mellitus status. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00674271.
10.1161/JAHA.118.008677
Associations of Carotid Intima-Media Thickness and Plaque Heterogeneity With the Risks of Stroke Subtypes and Coronary Artery Disease in the Japanese General Population: The Circulatory Risk in Communities Study.
Shimoda Saeko,Kitamura Akihiko,Imano Hironori,Cui Renzhe,Muraki Isao,Yamagishi Kazumasa,Umesawa Mitsumasa,Sankai Tomoko,Hayama-Terada Mina,Kubota Yasuhiko,Shimizu Yuji,Okada Takeo,Kiyama Masahiko,Iso Hiroyasu
Journal of the American Heart Association
Background Evidence on the associations of carotid intima-media thickness and carotid plaque characteristics with stroke subtypes and coronary artery disease risks in Asians is limited. This study investigated these associations in the Japanese general population. Methods and Results Maximum intima-media thicknesses of both the common carotid artery and internal carotid artery and carotid plaque characteristics were evaluated in 2943 Japanese subjects aged 40 to 75 years without history of cardiovascular disease. Subjects were followed up for a median of 15.1 years. Using a multivariate Cox proportional hazard model, we found that hazard ratios (HRs) and 95% CIs for the highest (≥1.07 mm) versus lowest (≤0.77 mm) quartiles of maximum intima-media thicknesses of the common carotid artery were 1.97 (1.26-3.06) for total stroke, 1.52 (0.67-3.41) for hemorrhagic stroke, 2.45 (1.41-4.27) for ischemic stroke, 3.60 (1.64-7.91) for lacunar infarction, 1.53 (0.69-3.41) for nonlacunar cerebral infarction, 2.68 (1.24-5.76) for coronary artery disease, and 2.11 (1.44-3.12) for cardiovascular disease (similar results were found for maximum intima-media thicknesses of the internal carotid artery). HRs(95% CIs) for heterogeneous plaque versus no plaque were 1.58 (1.09-2.30) for total stroke, 1.25 (0.58-2.70) for hemorrhagic stroke, 1.74 (1.13-2.67) for ischemic stroke, 1.84 (1.03-3.19) for lacunar infarction, 1.58 (0.80-3.11) for nonlacunar cerebral infarction, 2.11 (1.20-3.70) for coronary artery disease, and 1.71 (1.25-2.35) for cardiovascular disease. Conclusions Maximum intima-media thicknesses of the common carotid artery, maximum intima-media thicknesses of the internal carotid artery, and heterogeneous plaque were associated with the risks of stroke, lacunar infarction, coronary artery disease, and cardiovascular disease in Asians.
10.1161/JAHA.120.017020
Sex Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source.
Song Jae W,Cao Quy,Siegler James E,Thon Jesse M,Woo John H,Cucchiara Brett L
Journal of the American Heart Association
Background We examined sex differences in nonstenotic carotid plaque composition in patients with embolic stroke of undetermined source (ESUS). Methods and Results Patients with anterior circulation ischemic stroke imaged with neck computed tomographic angiography who met criteria for ESUS or had atrial fibrillation were identified. Patients with atrial fibrillation were included as a negative control. Semiautomated plaque quantification software analyzed carotid artery bifurcations. Plaque subcomponent (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core) volumes were compared by sex and in paired analyses of plaque ipsilateral versus contralateral to stroke. Multivariate linear regressions tested for associations. Ninety-four patients with ESUS (55% women) and 95 patients with atrial fibrillation (47% women) were identified. Men with ESUS showed significantly higher volumes of calcified plaque (63.9 versus 19.6 mm, <0.001), IPH (9.4 versus 3.3 mm, =0.008) and a IPH/lipid rich necrotic core ratio (0.17 versus 0.07, =0.03) in carotid plaque ipsilateral to stroke side than women. The atrial fibrillation cohort showed no significant sex differences in plaque volumes ipsilateral to stroke. Multivariate analyses of the ESUS cohort showed male sex was associated with IPH (β=0.49; 95% CI, 0.11-0.87) and calcium (β=0.78; 95% CI, 0.33-1.23). Paired plaque analyses in men with ESUS showed significantly higher calcified plaque (63.9 versus 34.1 mm, =0.03) and a trend of higher IPH (9.4 versus 7.5 mm, =0.73) and lipid rich necrotic core (59.0 versus 48.4 mm, =0.94) volumes. Conclusions Sex differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of nonstenosing carotid plaque as a stroke mechanism in men versus women.
10.1161/JAHA.120.020143
Carotid Atherosclerosis Predicts Blood Pressure Control in Patients With Hypertension: The Campania Salute Network Registry.
Journal of the American Heart Association
Background The 2018 European Society of Cardiology/European Society of Hypertension arterial hypertension guidelines do not recommend routine carotid ultrasound as a tool to identify hypertension-mediated organ damage, unless clinically indicated. However, carotid plaque (CP) is a strong correlate of increased arterial stiffness, which influences blood pressure (BP) control over time. Thus, we assessed whether evidence of CP at first visit could predict BP control during follow-up. Methods and Results From the CSN (Campania Salute Network) Registry, 6684 patients with hypertension had complete carotid ultrasound examination and were categorized by the presence of CP at baseline. Optimal BP control was defined as average BP <140/90 mm Hg and <135/85 during follow-up for office and home BP, respectively. At baseline, participants with CP (n=3061) were more likely to be men, to be older, to have diabetes, and to exhibit higher systolic BP, lower diastolic BP, worse lipid profile, and higher prevalence of left ventricular hypertrophy (all <0.0001) than patients without CP. Optimal office BP control was adjudicated in 54% with and 62% without CP (<0.0001), and optimal home BP in 51% with and 58% without CP (<0.01). Presence of CP was significantly associated with the reduced probability of controlled office BP during follow-up (both <0.0001), independently of significant effect of older age, male sex, higher baseline BP values, classes of medication, and presence of left ventricular hypertrophy, and only attenuated by duration of hypertension. Conclusions Presence of CP in treated patients with hypertension is associated with suboptimal BP control during follow-up, independently of worse metabolic profile and presence of left ventricular hypertrophy.
10.1161/JAHA.121.022345
Weight Change and Development of Subclinical Carotid Atherosclerosis Among Metabolically Healthy Adults: A Cohort Study.
Sinn Dong Hyun,Kang Danbee,Cho Soo Jin,Chang Yoosoo,Ryu Seungho,Song Young Bin,Paik Seung Woon,Hong Yun Soo,Zhao Di,Guallar Eliseo,Cho Juhee,Gwak Geum-Youn
The Journal of clinical endocrinology and metabolism
BACKGROUND:The benefit of weight loss for reducing cardiovascular disease (CVD) risk in metabolically healthy obese people is unknown. OBJECTIVES:We evaluated the association between weight change and incident subclinical carotid atherosclerosis (SCA) in metabolically healthy but overweight or obese subjects. METHODS:Cohort study of 3117 metabolically healthy overweight or obese adults who did not have any metabolic syndrome components or insulin resistance at baseline. SCA was assessed using carotid artery ultrasonography. The study outcome was the development of incident SCA among participants free of the disease at baseline. RESULTS:During 12 248 person-years of follow-up (median 3.42 years), 747 participants developed SCA. The proportions of participants with no reduction or increased weight, reduction in weight from 0.1% to 4.9%, and reduction in weight ≥ 5% during follow-up were 47.0%, 44.4%, and 8.6%, respectively. The fully-adjusted hazard ratios (HRs) for incident SCA in participants with a reduction in weight of 0.1% to 4.9% and ≥ 5% compared with those with no reduction or increased weight were 0.84 (95% CI, 0.72-0.98) and 0.66 (95% CI, 0.50-0.87), respectively. CONCLUSIONS:In a large cohort study of metabolically healthy but overweight or obese adult men and women, weight reduction was associated with a lower incidence of SCA. Our findings suggest that metabolically healthy overweight or obese subjects may benefit from weight reduction in terms of CVD risk.
10.1210/clinem/dgz040
Differences Between Anticoagulated Patients With Ischemic Stroke Versus Intracerebral Hemorrhage.
Journal of the American Heart Association
Background Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce. Methods and Results Cross-sectional study was done on consecutive oral anticoagulant-treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel-Oral-Anticoagulants-In-Stroke-Patients)-Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32-0.82], 0.48 [0.26-0.86], 0.55 [0.34-0.89], and 0.82 [0.75-0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87-14.04], 1.37 [1.04-1.81] per 10 years, 1.19 [1.10-1.29] per 10 mm Hg, and 1.81 [1.09-3.03]). Cerebral microbleeds and moderate-to-severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34-6.18], and 2.62 [1.28-5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31-0.90], 0.29 [0.05-0.97], 0.48 [0.30-0.76], and 0.32 [0.13-0.67]). Conclusions In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02353585.
10.1161/JAHA.121.023345
Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease.
Journal of the American Heart Association
Background Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that atherogenesis starts in the aorta, the CDACD (Cardiovascular Disease in Adolescents with Chronic Disease) study investigated preclinical aortic atherosclerosis in these adolescents. Methods and Results The cross-sectional CDACD study enrolled 114 adolescents 12 to 18 years old with chronic disorders including juvenile idiopathic arthritis, cystic fibrosis, obesity, corrected coarctation of the aorta, and healthy controls with a corrected atrial septal defect. Cardiovascular magnetic resonance was used to assess aortic pulse wave velocity and aortic wall thickness, as established aortic measures of preclinical atherosclerosis. Cardiovascular magnetic resonance showed a higher aortic pulse wave velocity, which reflects aortic stiffness, and higher aortic wall thickness in all adolescent chronic disease groups, compared with controls (<0.05). Age (β=0.253), heart rate (β=0.236), systolic blood pressure (β=-0.264), and diastolic blood pressure (β=0.365) were identified as significant predictors for aortic pulse wave velocity, using multivariable linear regression analysis. Aortic wall thickness was predicted by body mass index (β=0.248) and fasting glucose (β=0.242), next to aortic lumen area (β=0.340). Carotid intima-media thickness was assessed using ultrasonography, and was only higher in adolescents with coarctation of the aorta, compared with controls (<0.001). Conclusions Adolescents with chronic disease showed enhanced aortic stiffness and wall thickness compared with controls. The enhanced aortic pulse wave velocity and aortic wall thickness in adolescents with chronic disease could indicate accelerated atherogenesis. Our findings underscore the importance of the aorta for assessment of early atherosclerosis, and the need for tailored cardiovascular follow-up of children with chronic disease.
10.1161/JAHA.122.024675
Cumulative Blood Pressure in Early Adulthood and Coronary Artery Calcium and Carotid Intima-Media Thickness in Middle Age Among Adults With Maintained Blood Pressure of <130/80 mm Hg: A Post Hoc Analysis.
Journal of the American Heart Association
BACKGROUND:To examine the association of blood pressure (BP) levels with coronary artery calcium and carotid intima-media thickness (CIMT) in people with maintained BP below the hypertension range based on current definitions. METHODS AND RESULTS:In this post hoc analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) prospective observational cohort study conducted in 4 US cities, we examined 1233 study participants (mean [SD] age at year 20 examination was 45.3 [3.5] years; 65.4% women). Participants with BP assessments across 20 years and untreated BP of <130/80 mm Hg were included. Multivariable logistic or linear regression models, adjusted for age, sex, race, education, diabetes, body mass index, serum creatinine, smoking, alcohol intake, physical activity, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides, were used to examine the associations between cumulative BP measures with coronary artery calcium and CIMT. Higher long-term cumulative systolic BP and pulse pressure across early adulthood were associated with higher CIMT (both <0.001) but not coronary artery calcium in the multivariable-adjusted model. The associations remained significant even after adjustment for a single BP measurement at year 0 or year 20. The odds ratio (OR) of a maximal CIMT >1.01 mm was ≈50% higher per 1-SD increase in systolic BP (OR, 1.50 [95% CI, 1.19-1.88]) and pulse pressure (OR, 1.46 [95% CI, 1.19-1.79]). Similar findings for CIMT were observed among individuals with a coronary artery calcium score of 0 as well as those with maintained BP of <120/80 mm Hg throughout young adulthood. CONCLUSIONS:Long-term cumulative systolic BP and pulse pressure across early adulthood within the nonhypertensive range were associated with adverse midlife alterations in CIMT.
10.1161/JAHA.123.032091
Explanatory Power and Prognostic Implications of Factors Associated with Troponin Elevation in Acute Ischemic Stroke.
Journal of stroke
BACKGROUND AND PURPOSE:We investigated the impact of comorbidity burden on troponin elevation, with separate consideration of neurological conditions, in patients with acute ischemic stroke (AIS). METHODS:This prospective, observational cohort study consecutively enrolled patients with AIS for 2 years. Serum cardiac troponin I was repeatedly measured, and disease-related biomarkers were collected for diagnosis of preassigned comorbidities, including atrial fibrillation (AF), ischemic heart disease (IHD), myocardial hypertrophy (MH), heart failure (HF), renal insufficiency (RI), and active cancer. The severity of neurological deficits and insular cortical ischemic lesions were assessed as neurological conditions. Adjusted associations between these factors and troponin elevation were determined using a multivariate ordinal logistic regression model and area under the receiver operating characteristic curve (AUC). Cox proportional hazards model was used to determine the prognostic significance of comorbidity beyond neurological conditions. RESULTS:Among 1,092 patients (66.5±12.4 years, 63.3% male), 145 (13.3%) and 335 (30.7%) had elevated (≥0.040 ng/mL) and minimally-elevated (0.040-0.010 ng/mL) troponin, respectively. In the adjusted analysis, AF, MH, HF, RI, active cancer, and neurological deficits were associated with troponin elevation. The multivariate model with six comorbidities and two neurological conditions exhibited an AUC of 0.729 (95% confidence interval [CI], 0.698-0.759). In Cox regression, AF, IHD, and HF were associated with adverse cardio-cerebrovascular events, whereas HF and active cancer were associated with mortality. CONCLUSION:Troponin elevation in patients with AIS can be explained by the burden of comorbidities in combination with neurological status, which explains the prognostic significance of troponin assay.
10.5853/jos.2022.02012
Bleeding Risk of Dual Antiplatelet Therapy after Minor Stroke or Transient Ischemic Attack.
Wang Anxin,Meng Xia,Tian Xue,Johnston S Claiborne,Li Hao,Bath Philip M,Zuo Yingting,Xie Xuewei,Jing Jing,Lin Jinxi,Wang Yilong,Zhao Xingquan,Li Zixiao,Jiang Yong,Liu Liping,Wang Feng,Li Ying,Liu Jingyao,Wang Yongjun,
Annals of neurology
OBJECTIVE:This study was undertaken to identify the risk of bleeding events and potential risk factors within 90 days in patients who carried CYP2C19 loss-of-function alleles and received dual antiplatelet therapy after minor stroke or transient ischemic attack. METHODS:A total of 6,412 patients were enrolled from the CHANCE-2 (Clopidogrel with Aspirin in High-Risk Patients with Acute Non-disabling Cerebrovascular Events II) trial. The main outcome was any bleeding within 90 days defined by the criteria from GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries). RESULTS:A total of 250 (3.9%) bleeding events were reported, which occurred mainly within the 21 days of dual antiplatelet therapy (200 cases, 3.1%). Minor bleeding of the skin bruises, epistaxis, and gum bleeding were most frequent. Multivariate analysis showed that treatment with ticagrelor-aspirin compared with clopidogrel-aspirin was associated with increased bleeding (hazard ratio [HR] = 2.21, 95% confidence interval [CI] = 1.68-2.89, p < 0.001). Current smoking was associated with a lower risk of bleeding (HR = 0.70, 95% CI = 0.52-0.95, p = 0.02). Additionally, ticagrelor-aspirin compared with clopidogrel-aspirin was associated with higher risk of bleeding in patients aged <65 years (HR = 2.87, 95% CI = 1.95-4.22) and those without diabetes mellitus (HR = 2.65, 95% CI = 1.88-3.73; p for interaction = 0.04 and 0.03, respectively). INTERPRETATION:Bleeding events mostly occurred within the 21-day dual antiplatelet therapy stage and were generally mild. The risk of bleeding was greater in nonsmoking patients, and was associated with treatment with ticagrelor-aspirin compared with clopidogrel-aspirin, particularly in patients aged <65 years and nondiabetic patients. ANN NEUROL 2022;91:380-388.
10.1002/ana.26287
Age-related immune alterations and cerebrovascular inflammation.
Molecular psychiatry
Aging is associated with chronic systemic inflammation, which contributes to the development of many age-related diseases, including vascular disease. The world's population is aging, leading to an increasing prevalence of both stroke and vascular dementia. The inflammatory response to ischemic stroke is critical to both stroke pathophysiology and recovery. Age is a predictor of poor outcomes after stroke. The immune response to stroke is altered in aged individuals, which contributes to the disparate outcomes between young and aged patients. In this review, we describe the current knowledge of the effects of aging on the immune system and the cerebral vasculature and how these changes alter the immune response to stroke and vascular dementia in animal and human studies. Potential implications of these age-related immune alterations on chronic inflammation in vascular disease outcome are highlighted.
10.1038/s41380-021-01361-1
Relationship Among Diabetes, Obesity, and Cardiovascular Disease Phenotypes: A UK Biobank Cohort Study.
Diabetes care
OBJECTIVE:Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes. RESEARCH DESIGN AND METHODS:A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including carotid intima-media thickness (CIMT), arterial stiffness, left ventricular ejection fraction (LVEF), and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRRs) for myocardial infarction, ischemic stroke, and cardiovascular death, with normal-weight nondiabetes as comparator. RESULTS:Five percent of participants had diabetes (10% normal weight, 34% overweight, and 55% obese vs. 34%, 43%, and 23%, respectively, without diabetes). In the nondiabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness, and CCI and lower LVEF (P < 0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (P < 0.005), particularly in the normal-weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke, and cardiovascular mortality rose across increasing BMI categories without diabetes (P < 0.005); this was comparable in the diabetes groups (P-interaction > 0.05). Normal-weight diabetes had comparable adjusted cardiovascular mortality to obese nondiabetes (IRR 1.22 [95% CI 0.96-1.56]; P = 0.1). CONCLUSIONS:Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. While adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting that other factors underpin the high cardiovascular risk of normal-weight diabetes.
10.2337/dc23-0294
Mendelian Randomization Study of Obesity and Cerebrovascular Disease.
Annals of neurology
OBJECTIVE:To systematically investigate causal relationships between obesity and cerebrovascular disease and the extent to which hypertension and hyperglycemia mediate the effect of obesity on cerebrovascular disease. METHODS:We used summary statistics from genome-wide association studies for body mass index (BMI), waist-to-hip ratio (WHR), and multiple cerebrovascular disease phenotypes. We explored causal associations with 2-sample Mendelian randomization (MR) accounting for genetic covariation between BMI and WHR, and we assessed what proportion of the association between obesity and cerebrovascular disease was mediated by systolic blood pressure (SBP) and blood glucose levels, respectively. RESULTS:Genetic predisposition to higher BMI did not increase the risk of cerebrovascular disease. In contrast, for each 10% increase in WHR there was a 75% increase (95% confidence interval [CI] = 44-113%) in risk for large artery ischemic stroke, a 57% (95% CI = 29-91%) increase in risk for small vessel ischemic stroke, a 197% increase (95% CI = 59-457%) in risk of intracerebral hemorrhage, and an increase in white matter hyperintensity volume (β = 0.11, 95% CI = 0.01-0.21). These WHR associations persisted after adjusting for genetic determinants of BMI. Approximately one-tenth of the observed effect of WHR was mediated by SBP for ischemic stroke (proportion mediated: 12%, 95% CI = 4-20%), but no evidence of mediation was found for average blood glucose. INTERPRETATION:Abdominal adiposity may trigger causal pathological processes, partially independent from blood pressure and totally independent from glucose levels, that lead to cerebrovascular disease. Potential targets of these pathological processes could represent novel therapeutic opportunities for stroke. ANN NEUROL 2020;87:516-524.
10.1002/ana.25686
Evaluation of the Correlation Between Distribution Location and Vulnerability of Carotid Plaque in Patients with Transient Ischemic Attack.
Vascular health and risk management
Purpose:To analyze the relationship among distribution location, characteristics, and vulnerability of carotid plaque using CTA and provide more information on the risk factors of carotid atherosclerotic plaque. Patients and Methods:We retrospectively analyzed the CTA images of the head and neck of 93 patients with carotid atherosclerosis. Atherosclerosis was developed in 148 carotid arteries. The plaques were divided into a high-risk plaque group and a low-risk plaque group according to whether the plaques had high-risk characteristics. The maximum cross-sectional area of carotid artery bifurcation plaque on the axial image was selected, and the cross-sectional lumen was equally divided into four 90-degree sectors, ventral side wall, dorsal side wall, inner side wall, and outer side wall. The differences in the characteristics and distribution locations of the plaques in the two groups were analyzed. The characteristic parameters of the cross-sectional plaques at the bifurcation of the carotid artery. The logistic regression analysis was used to further analyze the risk factors associated with plaque vulnerability. Results:Among 148 carotid arteries,80 were classified as high-risk and 68 as low-risk groups. There were significant differences between the two groups concerning the thickness, length, maximum cross-sectional area, burden, and cross-sectional distribution of the plaques (P < 0.05). The plaque distribution on the dorsal side wall of the carotid bifurcation was higher in the high-risk group than that in the low-risk group (P < 0.05), dorsal side wall plaque-independent risk factors for the development of vulnerability of plaques in transient ischemic attack (TIA) patients (95% CI:1.522~6.991, P<0.05). Conclusion:High-risk plaques tend to occur on the dorsal side wall of the carotid bifurcation, whereas low-risk plaques tend to occur on the outer side wall of the carotid bifurcation.
10.2147/VHRM.S447418
Association Between Carotid Bifurcation Geometry and Atherosclerotic Plaque Vulnerability: A Chinese Atherosclerosis Risk Evaluation Study.
Jiang Peirong,Chen Zhensen,Hippe Daniel S,Watase Hiroko,Sun Bin,Lin Ruolan,Yang Zheting,Xue Yunjing,Zhao Xihai,Yuan Chun
Arteriosclerosis, thrombosis, and vascular biology
OBJECTIVE:Carotid bifurcation geometry has been believed to be a risk factor for the initiation of atherosclerosis because of its influence on hemodynamics. However, the relationships between carotid bifurcation geometry and plaque vulnerability are not fully understood. This study aimed to determine the association between carotid bifurcation geometry and plaque vulnerability using magnetic resonance vessel wall imaging. Approach and Results: A total of 501 carotid arteries with nonstenotic atherosclerosis were included from the cross-sectional, multicenter CARE II study (Chinese Atherosclerosis Risk Evaluation). Four standardized carotid bifurcation geometric parameters (bifurcation angle, internal carotid artery planarity, luminal expansion FlareA, and tortuosity Tort2D) were derived from time-of-flight magnetic resonance angiography. Presence of vulnerable plaque, which was characterized by intraplaque hemorrhage, large lipid-rich necrotic core, or disrupted luminal surface, was determined based on multicontrast carotid magnetic resonance vessel wall images. Vulnerable plaques (N=43) were found to occur at more distal locations (ie, near the level of flow divider) than stable plaques (N=458). Multivariable logistic regression showed that the luminal expansion FlareA (odds ratio, 0.45 [95% CI, 0.25-0.81]; =0.008) was associated with plaque vulnerability after adjustment for age, sex, maximum wall thickness, plaque location, and other geometric parameters. CONCLUSIONS:Smaller luminal expansion at carotid bifurcation is associated with vulnerable plaque. The finding needs to be verified with longitudinal studies and the underlying mechanism should be further explored with hemodynamics measurement in the future.
10.1161/ATVBAHA.119.313830
Significance of atherosclerotic plaque location in recanalizing non-acute long-segment occlusion of the internal carotid artery.
Scientific reports
To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.
10.1038/s41598-024-61938-y
Associations of plaque morphology and location with Intraplaque neovascularization in the carotid artery by contrast-enhanced ultrasound imaging.
Frontiers in neurology
Objective:Intraplaque neovascularization (IPN) is a known indicator of plaque vulnerability, and is thus considered a predictor of stroke. The morphology and location of the carotid plaque may be correlated with plaque vulnerability. Therefore, our study aimed to examine the associations of carotid plaque morphology and location with IPN. Methods:A total of 141 patients with carotid atherosclerosis (mean age, 64.99 ± 10.96 years) who underwent carotid contrast-enhanced ultrasound (CEUS) between November 2021 and March 2022 were retrospectively analyzed. IPN was graded according to the presence and location of microbubbles within the plaque. The association of IPN grade with carotid plaque morphology and location was evaluated using ordered logistic regression. Results:Of the 171 plaques, 89 (52%) were IPN Grade 0, 21 (12.2%) were Grade 1, and 61 (35.6%) were Grade 2. IPN grade significantly associated with both plaque morphology and location, with higher grades observed among Type III morphology and common carotid artery plaques. Significant negative association was further shown between IPN grade and serum high-density lipoprotein cholesterol (HDL-C) level. Plaque morphology and location, and HDL-C remained significantly associated with IPN grade after adjusting for confounding factors. Conclusion:The location and morphology of carotid plaques were significantly associated with the IPN grade on CEUS, and therefore show potential as biomarkers for plaque vulnerability. Serum HDL-C was also identified as a protective factor against IPN, and may play a role in the management of carotid atherosclerosis. Our study provided a potential strategy for identification of vulnerable carotid plaques and elucidated the important imaging predictors of stroke.
10.3389/fneur.2023.1097070
Shape and Location of Carotid Atherosclerotic Plaque and Intraplaque Hemorrhage: A High-resolution Magnetic Resonance Imaging Study.
Lu Mingming,Cui Yuanyuan,Peng Peng,Qiao Huiyu,Cai Jianming,Zhao Xihai
Journal of atherosclerosis and thrombosis
AIM:The present study aimed to investigate the association between shape and location of atherosclerotic plaques and intraplaque hemorrhage (IPH) in carotid arteries using magnetic resonance (MR) imaging. METHODS:Overall, 114 symptomatic patients (mean age: 64.9±10.9 years; 81 males) who underwent MR imaging and had advanced carotid plaques were included in analysis. IPH presence and carotid plaque shape and location (below and above bifurcation) were evaluated. The plaque shape was defined as follows: type-I: the arc-length of plaque is greater in the upstream; type-II: the arc-length of plaque in downstream and upstream is equal; and type-III: the arc-length of plaque is greater in downstream. The plaque shape and location were compared between plaques with and without IPH and their associations with IPH were determined. RESULTS:Of 181detectedplaques, 57 (31.5%) had IPH. Compared with plaques without IPH, those with IPH had higher incidence of the plaque shape of type-I (66.7% vs. 32.2%, P＜0.001), lower incidence of plaque shape of type-III (24.6% vs. 50.0%, P=0.001), and were more likely located above carotid bifurcation (71.9% vs. 48.4%, P=0.003). The plaque shape of type-I (OR, 4.01; 95%CI, 1.36-11.83; P=0.012) and location above bifurcation (OR, 3.21; 95%CI, 1.07-9.61; P=0.037) of carotid plaques were significantly associated with IPH after adjusting for confounder factors. CONCLUSIONS:Carotid plaque shape and location are significantly associated with the occurrence of IPH. Our findings could provide new insights for the pathogenesis of IPH and vulnerably plaques.
10.5551/jat.47449
Atherosclerotic plaque in the left carotid artery is more vulnerable than in the right.
Selwaness Mariana,van den Bouwhuijsen Quirijn,van Onkelen Robbert S,Hofman Albert,Franco Oscar H,van der Lugt Aad,Wentzel Jolanda J,Vernooij Meike
Stroke
BACKGROUND AND PURPOSE:Ischemic stroke is more often diagnosed in the left hemisphere than in the right. It is unknown whether this asymmetrical prevalence relates to differences in carotid atherosclerosis. We compared atherosclerotic plaque prevalence, severity, and composition between left and right carotid arteries. METHODS:In a population-based cohort, carotid MRI scanning was performed in 1414 stroke-free participants (≥45 years). Using a multisequence MRI protocol, we assessed the prevalence, stenosis, and thickness of the plaque and its predominant component (ie, lipid core, intraplaque hemorrhage, calcification, or fibrous tissue in each carotid artery). Differences between left and right side were tested using paired t tests, McNemar test and Generalized Estimating Equation analyses. RESULTS:The majority (85%) of the participants had bilateral carotid plaques. Unilateral plaques were twice more prevalent on the left than on the right side (67% versus 33%; P<0.001). Plaque thickness was also greater on the left (3.1±1.2 versus 2.9±1.3 mm; P<0.001); degree of stenosis did not differ. Intraplaque hemorrhage and fibrous tissue were more prevalent on the left (9.1 versus 5.9%; P<0.001 and 45.0 versus 38.5%; P<0.001), whereas calcification occurred more often on the right (37.4 versus 31.6% at the left; P<0.001). Lipid was equally distributed. CONCLUSIONS:Carotid atherosclerotic plaque size and composition are not symmetrically distributed. Predominance of intraplaque hemorrhage in left-sided carotid plaques suggests a greater vulnerability as opposed to right-sided plaques, which are more calcified and therefore considered more stable.
10.1161/STROKEAHA.114.005202
Correlation between of small dense low-density lipoprotein cholesterol with acute cerebral infarction and carotid atherosclerotic plaque stability.
QiaoZhen Xue,AiGuo Meng,Tong Wang,JingJing Li,HaiYing Liu
Journal of clinical laboratory analysis
BACKGROUND:Acute cerebral infarction (ACI) is seriously harmful to human health worldwide. However, at present, the risk of disease onset is still not accurately predicted for some people. METHODS:Five hundred and nineteen patients with ACI and 300 healthy controls were included in this study. We divided the patients into three groups according to the results of cervical artery contrast-enhanced ultrasound. Ninety-five patients were in the CAS without plaque group, 108 patients were in the stable plaque group, and 316 patients were in the unstable plaque group. TC, TG, HDL-C, LDL-C, and sdLDL-C were measured in all subjects. RESULTS:The level of small dense low-density lipoprotein cholesterol (sdLDL-C) in the ACI group was significantly higher than that in the control group (P < 0.001). Logistic regression analysis showed that sdLDL-C was an independent risk factor for ACI (OR = 1.067, 95% CI: 1.041-1.093, P < 0.001); serum sdLDL-C was significantly higher in the unstable plaque group than in the stable plaque group and plaque-free group (P < 0.05, P < 0.001); serum sdLDL-C was also higher in the stable plaque group than the plaque-free group (P < 0.001). Logistic regression analysis showed that sdLDL-C was an independent risk factor for unstable carotid plaques (OR = 1.053, 95% CI: 1.038-1.068, P < 0.001); Spearman correlation analysis showed that sdLDL-C test results were positively correlated with carotid plaque stability (r = 0.363, P < 0.001). CONCLUSION:Small dense low-density lipoprotein cholesterol is an independent risk factor for the onset of ACI and may be an early serum marker for this disease.
10.1002/jcla.22891
ApoB and Non-HDL Cholesterol Versus LDL Cholesterol for Ischemic Stroke Risk.
Annals of neurology
OBJECTIVE:Conflicting results have been reported on the association between lipids and risk of ischemic stroke. We tested the hypothesis that the burden of ischemic stroke attributable to either elevated apolipoprotein B (apoB) or non-high-density lipoprotein (non-HDL) cholesterol is higher than that attributable to elevated low-density lipoprotein (LDL) cholesterol. METHODS:We included 104,618 individuals from an ongoing cohort study, the Copenhagen General Population Study. The associations of quintiles of apoB, non-HDL cholesterol, and LDL cholesterol with risk of ischemic stroke were estimated by Cox proportional hazards regressions with 95% confidence intervals. With 1 quintile as reference, the proportion of ischemic stroke attributable to the 2 , 3 , 4 , and 5 quintiles of apoB, non-HDL cholesterol, and LDL cholesterol were estimated by population attributable fractions. RESULTS:Higher quintiles of apoB and non-HDL cholesterol were associated with increased risk of ischemic stroke (both trends: p < 0.0001), whereas for LDL cholesterol this association was somewhat attenuated (trend: p = 0.0005). A similar pattern was seen for population attributable fraction values. Compared to individuals in the 1 quintile, the combined proportion of ischemic stroke attributable to individuals in the 2 to 5 quintiles was 16.3% for apoB (levels >82 mg/dL), 14.7% for non-HDL cholesterol (>3.0 mmol/L; >117 mg/dL), and 6.8% for LDL cholesterol (>2.4 mmol/L; >94 mg/dL). INTERPRETATION:The proportion of ischemic stroke attributable to either elevated apoB or non-HDL cholesterol was double that attributable to elevated LDL cholesterol. ANN NEUROL 2022;92:379-389.
10.1002/ana.26425
Small Dense Low-Density Lipoprotein Cholesterol and Ischemic Stroke.
Annals of neurology
OBJECTIVE:For decades, it has been suggested that small dense low-density lipoprotein (sdLDL) may be particularly atherogenic. High levels of sdLDL are associated with an increased risk of ischemic heart disease; however, the association of sdLDL with ischemic stroke has not been explored in a large prospective study on the general population. We tested the hypothesis that high sdLDL cholesterol levels are associated with an increased risk of ischemic stroke. METHODS:This prospective study included 38,319 individuals from the Copenhagen General Population Study with fresh sample measurements of sdLDL cholesterol. Median follow-up time was 3.1 years. We observed 302 and 74 ischemic and hemorrhagic strokes from baseline in 2013 to 2017 to the end of follow-up in 2018. For comparison, we included estimates for large buoyant LDL cholesterol and total LDL cholesterol. RESULTS:Higher levels of sdLDL cholesterol were log-linearly associated with increased risk of ischemic stroke. Compared with individuals with sdLDL cholesterol in the lowest tertile (≤0.60 mmol/l; ≤23 mg/dl) the multivariable adjusted hazard ratio for ischemic stroke was 1.79 (95% confidence interval = 1.31-2.43) for the highest tertile (≥0.86 mmol/l; ≥33 mg/dl). Multivariable adjusted hazard ratios for ischemic stroke per 1 mmol/l (38.7 mg/dl) higher levels were 1.69 (1.28-2.22) for sdLDL cholesterol, 0.95 (0.78-1.16) for large buoyant LDL cholesterol, and 1.08 (0.93-1.25) for total LDL cholesterol. Hazard ratios were similar when further adjusting for body mass index (BMI) and diabetes mellitus in the biological pathway in combination with related lipids and lipoproteins. INTERPRETATION:Higher sdLDL cholesterol levels were robustly associated with increased risk of ischemic stroke. ANN NEUROL 2023;93:952-964.
10.1002/ana.26598
Neutrophil and monocyte ratios to high-density lipoprotein cholesterol as biomarkers in non-dipping hypertension.
Clinical and experimental hypertension (New York, N.Y. : 1993)
OBJECTIVE:To investigate the level and significance of neutrophils to high-density lipoprotein cholesterol ratio (NHR) and monocytes to high-density lipoprotein cholesterol ratio (MHR) in patients with non-dipping hypertension. METHODS:A total of 228 patients were retrospectively enrolled in the study. They were divided into the dipping hypertension group ( = 76), the non-dipping hypertension group ( = 77) and the control group ( = 75) according to 24-h ambulatory blood pressure monitoring system (ABPM) recordings. NHR and MHR were calculated and compared statistically. Receiver operating characteristic (ROC) curve analyses were performed for NHR and MHR. Binary logistic regression analyses were introduced to investigate the independent associations of NHR and MHR with non-dipping hypertension. RESULTS:The NHR and MHR were significantly higher in the non-dipping hypertension group compared with the control group ( = .001, < .001, respectively) and the dipping hypertension group ( = .039, = .003, respectively). According to ROC curve analyses, NHR>73.35 and MHR>7.54 were regarded as high-risk groups. The area under the curve (AUC) was 0.642 ( < .001) for NHR and 0.718 ( < .001) for MHR. In multivariate analysis, compared with NHR, only MHR was still recognized as a marker for detection of non-dipping hypertension (odds ratio [OR]: 1.208, 95% confidence interval [CI]: 1.076 to 1.356, = .001). CONCLUSIONS:Our data indicated that not NHR but MHR as new composite marker of inflammation and lipid metabolism may predict non-dipping hypertension to some extent.
10.1080/10641963.2023.2210785
Correlation Between Cerebral Microbleeds and Vulnerable Plaque in Patients with Severe Carotid Artery Stenosis; Comparative Magnetic Resonance Imaging Study.
Hori Satoshi,Hori Emiko,Shibata Takashi,Umemura Kimiko,Okamoto Soushi,Kubo Michiya,Horie Yukio,Kuroda Satoshi
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
GOAL:There are an increasing idea that the inflammation contributes to vascular diseases in various organs. The pathogenesis of both cerebral small vessel disease such as cerebral microbleeds and carotid plaque may be associated with chronic inflammation. This study was aimed to evaluate the correlation between microbleeds and carotid plaque characteristics. MATERIALS AND METHODS:This study enrolled 85 patients who underwent surgical/endovascular treatments for carotid artery stenosis between January 2009 and July 2016. Their clinical data were precisely analyzed. T2*-weighted magnetic resonance (MR) imaging was performed to detect the cerebral microbleeds. The carotid plaque with high signal intensity on T1-weighted MR imaging was categorized into vulnerable plaque. FINDINGS:The microbleeds was detected in 17 of 85 (20%). The prevalence of vulnerable carotid plaque and previous symptomatic lacunar infarction was significantly greater in the patients with microbleeds than in those without (P = .001 and P = .03, respectively). Multiple logistic regression analysis showed that the vulnerable plaque was significantly associated with the presence of microbleeds when adjusted for age, alcohol intake, antiplatelet drug use, the presence of previous symptomatic lacunar infarction, and coronary artery disease (P = .009, OR = 5.38, 95% CI = 1.51-21.0). CONCLUSIONS:These findings suggest the correlation between microbleeds and vulnerable plaque in patients with severe (>70%) carotid artery stenosis. Systemic, chronic inflammation may play a key role in both small and large arteries' disease of the brain. The knowledge may be valuable to fully understand the entity of cerebrovascular diseases as one of systemic, chronic inflammation.
10.1016/j.jstrokecerebrovasdis.2019.07.016
[Correlation between unilateral internal carotid artery stenosis and asymmetric distribution of enlarged perivascular spaces in patients with acute cerebral infarction].
Zhonghua yi xue za zhi
To explore the correlation between unilateral internal carotid artery (ICA) stenosis and asymmetrical distribution of enlarged perivascular spaces (EPVS) in patients with acute cerebral infarction. Acute cerebral infarction patients with unilateral ICA stenosis hospitalized in Changzhou Second People's Hospital from October 2020 to December 2021 were collected. Routine cranial MRI and CT angiography were completed for each patient. The 3D Slicer software was used to quantitatively analyze the volume of patient's EPVS. Patients were divided into moderate stenosis group and severe stenosis/occlusion group according to the degree of ICA stenosis. Baseline data were compared between the two groups. Patients were further divided into three groups: moderate stenosis, severe stenosis and occlusion groups, and the ipsilateral and contralateral EPVS volume of ICA stenosis patients was compared. The asymmetry index (AI) was calculated for EPVS in the basal ganglia region (BG-EPVS) and EPVS in the centrum semiovale (CSO-EPVS). Patients with AI≥0.2 were included in the EPVS asymmetry group, while the rest were in the EPVS symmetry group, and the degree of unilateral ICA stenosis was compared between the two groups. Multivariate logistic regression model was used to analyze the relationship between ICA severe stenosis/occlusion and the asymmetric distribution of BG-EPVS. A total of 122 patients (96 males and 26 females) were enrolled, aged (70±10) years, with 81 cases in the unilateral ICA severe stenosis/occlusion group (46 cases of severe stenosis and 35 of occlusion) and 41 cases in the moderate stenosis group. Patients in the unilateral ICA severe stenosis/occlusion group had greater BG-EPVS volume [(4.08±0.76) mm]and proportion of asymmetric distribution of BG-EPVS [75.3%(61/81)] than those of the moderate stenosis group [(3.12±0.85) mm and 39.0% (16/41)], with statistically significant differences (both <0.001). The BG-EPVS volumes of the ipsilateral side of the stenosis in the severe stenosis group and the occlusion group [(3.34±0.86) mm and (3.93±0.60) mm] were significantly greater than those of the contralateral side [(2.65±1.28) mm and (3.21±0.88) mm], with statistically significant differences (both <0.001). Correlation analysis indicated that the degree of unilateral ICA stenosis was positively correlated with the BG-EPVS volume on the stenosis side (=0.62, 0.001). Further comparison of the degree of unilateral ICA stenosis between the EPVS symmetric and asymmetric groups showed that the proportion of unilateral ICA severe stenosis/occlusion in the BG-EPVS asymmetry group was higher than that in the symmetric group [79.2%(61/77) vs 44.4%(20/45),<0.001]. Multivariate logistic regression analysis showed that unilateral ICA severe stenosis/occlusion (=4.280, 95%: 1.743-10.508, =0.002) and age (=1.055, 95%: 1.001-1.112, =0.044) were risk factors for asymmetric distribution of BG-EPVS. The severe stenosis/occlusion of the unilateral ICA and age are the risk factors for the asymmetric distribution of the BG-EPVS in patients with acute cerebral infarction. The ipsilateral EPVS volume of unilateral ICA stenosis is larger than that of the contralateral side, and the degree of ICA stenosis is positively correlated with the severity of BG-EPVS.
10.3760/cma.j.cn112137-20220601-01219
The Relationship between the Mean Platelet Volume and Carotid Atherosclerosis and Prognosis in Patients with Acute Cerebral Infarction.
BioMed research international
OBJECTIVE:To investigate the relationship between mean platelet volume (MPV) level and carotid atherosclerosis and prognosis in patients with acute cerebral infarction. A retrospectively included 160 patients with acute cerebral infarction classified by TOAST classification as aortic atherosclerosis as the observation group. To analyze the relationship between MPV and carotid atherosclerosis, and use receiver operating characteristic (ROC) curves to analyze the role of MPV in predicting the prognosis of acute cerebral infarction in the observation group, grouping patients with different MPV by cut-off value, and analyze the differences in factors between the two groups of patients. RESULTS:MPV has a positive correlation with carotid atherosclerosis in patients with acute cerebral infarction. Multivariate logistic regression analysis revealed that increased MPV was an independent predictor of poor functional outcome in patients with acute cerebral infarction (Odds Ratio (OR): 6.152, 95% CI: 2.385-13.625, < 0.01). ROC curve analysis showed that the area under the curve for MPV to predict poor prognosis was 0.868 (95% CI: 0.787-949, < 0.01). The cutoff value, sensitivity, and specificity were 12.65, 76.2%, and 87.6%. Compared with patients with MPV < 12.65 at admission, patients with higher MPV levels (MPV ≥ 12.65) at admission have larger infarct size, more severe carotid artery stenosis, poor short-term prognosis, and higher mortality. CONCLUSION:MPV level is closely related to the degree of carotid atherosclerosis in patients with acute cerebral infarction, and it is also an independent predictor of poor prognosis in patients with acute cerebral infarction at 3 months.
10.1155/2020/6685740
Carotid plaques and neurological impairment in patients with acute cerebral infarction.
Ni Tongtian,Fu Yi,Zhou Wei,Chen Min,Shao Jianwei,Zhou Weijun,Mao Enqiang,Chen Erzhen
PloS one
OBJECTIVE:To determine whether the coexistence of carotid atherosclerosis plaque affects the neurological function of cerebral infarction. METHODS:A total of 1078 patients with acute cerebral infarction were enrolled, all patients were divided into carotid plaque group (n = 702) and non-carotid plaque group (n = 376). Meanwhile, all patients were divided into mild group (n = 624) and moderate to severe group (n = 454). The difference of the incidence of carotid plaque between the mild and moderate to severe group was analyzed. RESULTS:In the 1078 patients with cerebral infarction, the NIHSS score in the carotid plaque group was significantly higher than that in the non-carotid plaque group (P<0.05). The number of mild cases without carotid artery plaque group was larger than that of plaque group (P<0.05), and the number of moderate to severe cases in carotid plaque group was larger than that in non-plaque group (P<0.05). In patients with carotid atherosclerotic plaque, the risk of moderate to severe cerebral infarction was 2.11 times higher than that without carotid artery plaque. Lastly, patients with single plaques were 1.82 times more likely to develop moderate to severe cerebral infarction than those without carotid plaque, while patients with multiple carotid plaques were 2.41 times higher to get moderate or severe cerebral infarction than those without carotid plaque. CONCLUSIONS:The incidence of carotid atherosclerotic plaques may be related to neurological deficits in patients with acute cerebral infarction.
10.1371/journal.pone.0226961
Trajectories of Lipid Profile and Risk of Carotid Atherosclerosis Progression: A Longitudinal Cohort Study.
Nutrients
BACKGROUND:Early assessment of carotid atherosclerotic plaque characteristics is essential for atherosclerotic cardiovascular disease (ASCVD) risk stratification and prediction. We aimed to identify different trajectories of lipid profiles and investigate the association of lipid trajectories with carotid atherosclerosis (CAS) progression in a large, longitudinal cohort of the Chinese population. METHODS:10,412 participants aged ≥18 years with ≥2 times general health checkups were included in this longitudinally prospective cohort study at Peking University Third Hospital. We used latent class trajectory models to identify trajectories of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) over follow-up time (757 days, IQR: 388-844 days). RESULTS:Participants with carotid plaque were more likely to be older, male, have higher body mass index, have a higher prevalence of hypertension and diabetes, and have a higher level of blood pressure, TG, TC, and LDL-C, compared with carotid intima-media thickness (cIMT) and normal group. Subjects were trichotomized according to different trajectory patterns into stable, moderate-stable, and elevated-increasing classes. TC ≥ 5.18 mmol/L and moderate-stable class (hazard ratio (HR): 1.416, 95% confidence interval (CI): 1.285-1.559, : 0.000), TG ≥ 1.70 mmol/L and moderate-stable class (HR: 1.492, 95% CI: 1.163-1.913, : 0.002), TG ≥ 1.70 mmol/L and elevated-increasing class (HR: 1.218, 95% CI: 1.094-1.357, : 0.000), LDL-C ≥ 3.36 mmol/L and stable class (HR: 1.500, 95% CI: 1.361-1.653, : 0.000) were statistically significant associated with CAS progression compared with the reference group. CONCLUSIONS:Borderline elevated baseline lipid (TC, TG, and LDL-C) with stable and elevated-increasing trajectories were associated with CAS progression. Long-term strategies for low-level lipid are beneficial for ASCVD management.
10.3390/nu14153243
Plasma Betatrophin Levels and Carotid Atherosclerosis.
Disease markers
AIMS:Betatrophin is a recently identified circulating adipokine that may affect lipid and glucose metabolism. However, the association between plasma betatrophin levels and carotid atherosclerosis has not been elucidated. METHODS:We investigated plasma betatrophin levels in 153 subjects undergoing carotid ultrasonography. The severity of plaque was evaluated as plaque score. RESULTS:Of the 153 subjects, plaque was found in 63 (41%). Plasma betatrophin levels were higher in 63 subjects with plaque than in 90 without plaque (median 906 vs. 729 pg/mL, < 0.025). A stepwise increase in betatrophin levels was found depending on the plaque score: 729 pg/mL in score = 0 ( = 90), 802 pg/mL in score = 1 ( = 31), and 978 pg/mL in score ≥ 2 ( = 32) ( < 0.01). In particular, betatrophin levels in subjects with score ≥ 2 were higher than in those with score = 0 ( < 0.05). Moreover, betatrophin levels correlated with plaque score ( = 0.23, < 0.01), but no significant correlation was found between betatrophin levels and triglyceride or HbA1c levels. The percentage of subjects with betatrophin > 800 pg/mL was higher in subjects with plaque than in those without plaque (65% vs. 44%) and was highest in score ≥ 2 (78%) ( < 0.005). In the multivariate analysis, betatrophin level was not a significant factor for the presence of plaque but was a significant factor for plaque score ≥ 2, independent of atherosclerotic risk factors. The odds ratio for score ≥ 2 was 4.9 (95% CI = 1.9-12.8) for betatrophin > 800 pg/mL. CONCLUSIONS:Plasma betatrophin levels were found to be high in subjects with carotid plaque and to be associated with the severity of plaque. Betatrophin may play a role in the progression of carotid atherosclerosis.
10.1155/2019/4214650
Plaque Length Predicts the Incidence of Microembolic Signals in Acute Anterior Circulation Stroke.
Zhao Liming,Zhao Hongqin,Xu Yicheng,Zhang Aijuan,Zhang Jiatang,Tian Chenglin
Disease markers
Microembolic signals (MES) of the carotid artery are associated with plaque destabilization and reoccurrence of stroke. Previous studies have focused primarily on the degree of carotid artery stenosis and plaque components, and the relationship between plaque length and microembolic sign has received little attention. We aimed to find the association between carotid plaque length (CPL) and the presence of MES. We conducted a retrospective observational cross-sectional study. A total of 84 acute anterior-circulation ischemic stroke/transient ischemic attack (TIA) patients with carotid artery atherosclerosis were classified into an MES-positive (MES+) group and MES-negative (MES-) group. We measured multiple parameters of carotid plaque size (length, thickness) in each patient and evaluated the relationship between different plaque parameters and occurrence of MES. We found that male, carotid artery stenosis (CAS), CPL, carotid plaque thickness (CPT), and intima-media thickness (IMT) of the carotid artery were each significantly different between two groups (all < 0.05). The multivariate analysis showed CPL (odds ratio (OR), 1.109; 95% CI, 1.044-1.177; = 0.001) to be independently associated with the presence of MES. The areas under the ROC curves (AUCs) for CPL for predicting MES were 0.777 (95% CI, 0.640-0.914; < 0.001). The cutoff value of CPL for predicting MES was 16.7 mm, with a sensitivity of 88.2% and a specificity of 77.6%. We found that CPL was a meaningful independent predictor of MES. Therefore, CPL may be useful for risk stratification of long and nonstenotic plaques in anterior circulation stroke.
10.1155/2021/2005369
Prevalence of Obstructive Sleep Apnoea and Its Association With Atherosclerotic Plaques in a Cohort of Subjects With Mild-Moderate Cardiovascular Risk.
Archivos de bronconeumologia
INTRODUCTION:Classic cardiovascular risk factors do not explain all the cardiovascular events. Obstructive sleep apnoea (OSA) has been proposed as a potential and prevalent cardiovascular risk factor. Our study aimed to describe the prevalence of OSA in a middle-aged cohort with mild-moderate cardiovascular risk and evaluate its association with atherosclerotic disease. METHODS:This is an observational cross-sectional ancillary study of the ILERVAS project which was aimed to study subclinical arterial disease in a cohort with mild-moderate cardiovascular risk. In a sample of consecutive subjects, we performed a sleep study and evaluate OSA prevalence and its association with carotid and femoral atheroma plaques and atherosclerotic burden. RESULTS:Overall, 966 subjects with a median age of 57 years (25-75th percentile; 52-62) and a body mass index (BMI) of 28.5kg/m (25.6-31.6) were included. Of these, 72.6% (69.7%-75.3%) had OSA (apnoea-hypopnoea index (AHI)≥5/h); 35.7% (32.8%-38.8%) had mild OSA (AHI 5-14.9/h) and 36.9% (33.9%-39.9%) had moderate/severe OSA (AHI≥15/h). Mean oxygen saturation and the percentage of time with oxygen saturation<90% (CT90) were associated with atherosclerotic burden (e (95%CI) 0.932 (0.892, 0.974); 1.005 (1.002, 1.009), respectively) and total plaque (OR (95%CI) 0.88 (0.797,0.971); 1.013 (1.004,1.021), respectively). No association with the AHI or oxygen desaturation index was found. CONCLUSIONS:This study confirms a high prevalence of OSA in patients with mild-moderate cardiovascular risk and shows an association between atherosclerotic burden, total and femoral plaque with CT90 and mean oxygen saturation, suggesting the importance of OSA-related hypoxaemia in the induction of atherosclerotic disease.
10.1016/j.arbres.2021.01.026
Measurement of carotid plaque burden.
Spence J David
Current opinion in lipidology
PURPOSE OF REVIEW:To describe the uses of measurement of carotid plaque burden, as total plaque area (TPA), total plaque volume (TPV), and vessel wall volume (VWV), which includes plaque burden and wall volume. RECENT FINDINGS:Measurement of plaque burden is useful for risk stratification, research into the genetics and biology of atherosclerosis, for measuring effects of new therapies for atherosclerosis, and for treatment of high-risk patients with severe atherosclerosis. SUMMARY:Measurement of plaque burden is far superior to measurement of carotid intima-media thickness (IMT) in many ways, and should replace it. Vessel wall volume can be measured in persons with no plaque as an alternative to IMT.
10.1097/MOL.0000000000000706
Relationship of the Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio with a Vulnerable Plaque in Patients with Severe Carotid Artery Stenosis: A Case-Control Study in the Han Chinese Population.
Current neurovascular research
BACKGROUND:Carotid plaque is often an important factor in ischemic stroke after it changes from stable to vulnerable, and low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) are associated with plaque vulnerability. We aimed to investigate whether the LDL-c/HDL-c ratio, an easily available and novel biomarker, is associated with vulnerable plaques and enhances the warning effect on vulnerability compared to LDL-c or HDL-c alone. METHODS:We conducted a retrospective study of 187 patients with severe CAS admitted to the Department of Vascular Surgery at the Nanjing Drum Tower Hospital from January 2019 to July 2021. They were divided into a stable plaque group and a vulnerable plaque group according to carotid ultrasonography, carotid angiography (CTA), and plaque pathology. Baseline information was collected and compared between the two groups. Correlation analysis was used to determine the degree of correlation between clinical variables. Univariate and multifactor logistic regression analyses were used to examine independent risk factors for vulnerable plaque in patients with severe CAS. Receiver operating characteristic (ROC) curves were used to assess the capacity of LDL-c/HDL-c to predict the occurrence of vulnerable plaque. RESULTS:The age of the vulnerable plaque group was 68.12 ± 8.90 years, with 85 males (89.91%); the age of the stable plaque group was 68.77 ± 8.43 years, with 70 males (89.74%). Multivariate logistic regression analysis showed that LDL-c/HDL-c, smoking and diabetes were independent risk factors for vulnerable plaque (all P <0.05). The risk of vulnerable plaque was 4.78-fold greater in the highest LDL-c/HDL-c quartile (≥ 2.63) than in the lowest quartile (≤ 1.31) (P-trend <0.001), and the area under the ROC curve for LDL-c/HDL-c (AUC=0.681, P <0.001) was higher than that for LDL-c and HDL-c. CONCLUSION:LDL-c/HDL-c, smoking and diabetes were independent risk factors for vulnerable plaque in patients with severe CAS, and LDL-c/HDL-c had a higher predictive value for the presence of vulnerable plaque compared with other lipid parameters.
10.2174/1567202619666220629160733
Serum insulin levels are associated with vulnerable plaque components in the carotid artery: the Rotterdam Study.
European journal of endocrinology
BACKGROUND:To investigate the association between fasting serum insulin and glucose levels with atherosclerotic plaque composition in the carotid artery. Impaired insulin and glucose levels are implicated in the etiology of cardiovascular disease; however, their influence on the formation and composition of atherosclerotic plaque remains unclear. METHODS:In 1740 participants (mean age 72.9 years, 46% women, 14.4% diabetes mellitus) from the population-based Rotterdam Study, we performed carotid MRI to evaluate the presence of calcification, lipid core, and intraplaque hemorrhage in carotid atherosclerosis. All participants also underwent blood sampling to obtain information on serum insulin and glucose levels. Using logistic regression models, we assessed the association of serum insulin and glucose levels (per s.d. and in tertiles) with the different plaque components, while adjusting for sex, age, intima-media thickness, and cardiovascular risk factors. RESULTS:Serum insulin levels were associated with the presence of intraplaque hemorrhage (adjusted odds ratio (OR): 1.42 (95% CI: 1.12-1.7)) We found no association with the presence of calcification or lipid core. Sensitivity analyses restricted to individuals without diabetes mellitus yielded similar results. No associations were found between serum glucose levels and any of the plaque components. CONCLUSIONS:Serum insulin levels are associated with the presence of vulnerable components of carotid plaque, specifically with intraplaque hemorrhage. These findings suggest a complex role for serum insulin in the pathophysiology of carotid atherosclerosis and in plaque vulnerability.
10.1530/EJE-19-0620
Carotid Plaque With High-Risk Features in Embolic Stroke of Undetermined Source: Systematic Review and Meta-Analysis.
Stroke
Background and Purpose- An ipsilateral mild carotid stenosis, defined as plaque with <50% luminal narrowing, is identified in nearly 40% of patients with embolic stroke of undetermined source and could represent an unrecognized source of atheroembolism. We aimed to summarize data about the frequency of mild carotid stenosis with high-risk features in embolic stroke of undetermined source. Methods- We searched Pubmed and Ovid-Embase for studies reporting carotid plaque imaging features in embolic stroke of undetermined source. The prevalence of ipsilateral and contralateral mild carotid stenosis with high-risk features was pooled using random-effect meta-analysis. Results- Eight studies enrolling 323 participants were included. The prevalence of mild carotid stenosis with high-risk features in the ipsilateral carotid was 32.5% (95% CI, 25.3-40.2) compared with 4.6% (95% CI, 0.1-13.1) in the contralateral carotid. The odds ratio of finding a plaque with high-risk features in the ipsilateral versus the contralateral carotid was 5.5 (95% CI, 2.5-12.0). Conclusions- Plaques with high-risk features are 5 times more prevalent in the ipsilateral compared with the contralateral carotid in embolic stroke of undetermined source, suggesting a relationship to stroke risk.
10.1161/STROKEAHA.119.027272
Association between non-high-density lipoprotein cholesterol levels and asymptomatic vulnerable carotid atherosclerotic plaques.
Wu J,Zhang J,Wang A,Chen S,Wu S,Zhao X
European journal of neurology
BACKGROUND AND PURPOSE:Carotid atherosclerosis, especially rupture of plaques, is related to cerebrovascular diseases. Non-high-density lipoprotein cholesterol (non-HDL-C) is relevant to cerebrovascular diseases and may be a potential risk factor. We designed this study to investigate the association between non-HDL-C and the prevalence of asymptomatic vulnerable carotid atherosclerotic plaques. METHODS:We enrolled 2888 participants who underwent carotid atherosclerotic plaque detection and non-HDL-C measurement, with no history of taking lipid-lowering agents, from the Asymptomatic Polyvascular Abnormalities in Community study. We used multivariable logistic regression to estimate the association between non-HDL-C levels and the presence of asymptomatic vulnerable carotid atherosclerotic plaques. RESULTS:In our study, 1505 subjects had asymptomatic vulnerable carotid atherosclerotic plaques and 1383 subjects had stable plaques. After adjustment for confounding factors, the odds ratios for vulnerable plaques of non-HDL-C levels in the middle and highest tertile groups were 1.02 (95% confidence interval, 0.84-1.23) and 1.50 (95% confidence interval, 1.23-1.82), respectively (P trend < 0.01). CONCLUSION:In our community-based observational and cross-sectional study, non-HDL-C level was a significant risk factor for the occurrence of asymptomatic vulnerable carotid plaques.
10.1111/ene.13973
High Dietary Inflammatory Index Is Associated With Increased Plaque Vulnerability of Carotid in Patients With Ischemic Stroke.
Peng Min,Wang Ling,Xia Yaqian,Tao Lei,Liu Yujing,Huang Feihong,Li Shun,Gong Xiuqun,Liu Xinfeng,Xu Gelin
Stroke
BACKGROUND AND PURPOSE:Long-term dietary patterns can influence the intensity of systemic inflammation and, therefore, the development of atherosclerosis. This study aimed to evaluate the association between dietary inflammatory index (DII) and vulnerability characteristics of carotid atherosclerotic plaques in patients with ischemic stroke. METHODS:Patients with ischemic stroke within 7 days of onset were enrolled. DII was calculated from 32 food components with the help of a food frequency questionnaire. Vulnerable plaque was defined as presence of artery positive remodeling (remodeling index >1.1) and low CT attenuation plaques (<35 HU) on carotid arteries by computed tomography angiography. RESULTS:Of the 398 enrolled patients, 144 (36.2%) were detected with vulnerable plaque. Their DII ranged from -4.58 to 4.18. Patients with vulnerable plaques consumed less nutrients with anti-inflammatory properties, less fruits and vegetables (85.6±64.3 versus 94.6±74.4 g/d, =0.027), and less nuts (5.66±7.14 versus 8.84±15.9 g/d, =0.024) than patients without vulnerable plaques. Patients with vulnerable plaque had higher DII than patients without vulnerable plaque (-0.26±1.54 versus -0.64±1.53, =0.018). Logistic regression analysis revealed that DII was associated with vulnerable plaques after adjusted for major confounding factors (odds ratio=1.307; 95% CI, 1.113-1.533). CONCLUSIONS:DII is associated with the vulnerability of carotid plaques in patients with ischemic stroke. Considering a possible causal relationship, the mechanisms underlying the association between diet and atherosclerosis warrant further study.
10.1161/STROKEAHA.120.029035
Association between carotid artery plaque inflammation and brain MRI.
Saba Luca,Lai Letizia,Lucatelli Pierleone,Sanfilippo Roberto,Montisci Roberto,S Suri Jasjit,Faa Gavino
Journal of neuroradiology = Journal de neuroradiologie
PURPOSE:To explore the association between presence of inflammatory cells in the carotid plaques surgically treated and brain MRI findings. MATERIAL AND METHODS:Forty consecutive patients were prospectively analyzed. Brain MRI was performed with a 1.5 Tesla scanner and infacts (lacuna and non-lacunar) pertinence of the anterior circulation were recorded. All patients underwent carotid endarterectomy "en bloc"; carotid plaques histological sections were prepared and immuno-cytochemical analysis was performed to characterize and quantify the presence of inflammatory cells. ROC curve analysis, Pearson Rho correlation and Mann-Whitney test were applied. RESULTS:The immuno-cytochemical analysis demonstrated that plaques of symptomatic patients (stroke\TIA; n = 25) had more inflammatory cells, mainly macrophages (CD68) compared with plaques of patients without symptoms (Mann-Whitney = P < 0.001, ROC curve area = 0.901). Correlation analysis showed a statistically significant association between the number of brain non-lacunar infarcts and the entity of macrophages (P < 0.001); whereas no association with lacunar infarcts (P = 0.1934) was found. CONCLUSION:Results of this preliminary study suggest that the presence and amount of inflammatory cells within carotid artery plaque is associated with cerebrovascular events and with the number of MRI brain detectable infarct.
10.1016/j.neurad.2018.10.004
Serum LDL-C/HDL-C ratio and the risk of carotid plaques: a longitudinal study.
BMC cardiovascular disorders
BACKGROUND:Dyslipidemia contributes to an increased risk of carotid atherosclerosis. However, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and carotid plaque formation has not been well documented. This study aims to assess the role of LDL-C/HDL-C in the risk of carotid plaque formation in a Chinese population. METHODS:We followed 2,191 participants who attended the annual routine health examination. Cox proportional hazards regression, restricted cubic spline (RCS), and subgroup analysis were applied to evaluate the association between the LDL-C/HDL-C ratio and carotid plaques. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS:Among 2,191 participants, 388 had incident carotid plaques detected, with a median follow-up time of 1.05 years. Compared with subjects younger than 45 years, those aged 45 to 59 years (HR: 2.00, 95% CI: 1.55-2.58) and over 60 years (HR: 3.36, 95% CI: 2.47-4.58) had an increased risk of carotid plaque formation. Males (HR: 1.26, 95% CI: 1.01-1.56), diabetes (HR: 1.46, 95% CI: 1.06-2.01) and a high LDL-C/HDL-C ratio (HR: 1.22, 95% CI: 1.07-1.38) were significantly linked with the occurrence of carotid plaques. After adjusting for potential confounding factors, we observed that a high LDL-C/HDL-C ratio promoted carotid plaque events (HR: 1.30, 95% CI: 1.12-1.50). The RCS analysis revealed a significant nonlinear association. The association was stronger among females (P-interaction < 0.05). CONCLUSION:A high LDL-C/HDL-C ratio could accelerate the occurrence of carotid plaques. Older men with diabetes and dyslipidemia are the critical target population. Women may be more likely to benefit from lipid-lowering interventions and thus avoid carotid plaque formation.
10.1186/s12872-022-02942-w
Association between carotid intima media thickness and small dense low-density lipoprotein cholesterol in acute ischaemic stroke.
Zhou Peiyang,Shen Yan,Wang Lingyun,Cao Zhihua,Feng Wenmin,Liu Jincheng,Wang Lijun,Meng Peng,Yang Jinbo,Xu Wang-Yang,Gao Ping
Lipids in health and disease
BACKGROUND:Intima-media thickness (IMT) and small dense low-density lipoprotein cholesterol (sdLDL-C) have been reported to be related to atherosclerosis and stroke. This study is trying to explore the association between IMT and sdLDL-C in Chinese acute ischaemic stroke (AIS) subjects. METHODS:This study enrolled total 368 consecutive AIS patients and 165 non-AIS controls from November 2016 to February 2019. Mean IMT and carotid plaques were measured by using carotid ultrasonography method. Blood glucose and lipid parameters were measured by using an automatic biochemical instrument. SdLDL-C was detected by using the Lipoprint LDL system. IMT > 1.0 mm was defined as increased IMT. Plaque stability based on the nature of the echo was determined by ultrasound examination. Risk factors for IMT were identified by using multivariate logistic regression analysis. A logistic regression model was established to predict AIS risk. Python software (Version 3.6) was used for the statistical analysis of all data. RESULTS:The carotid IMT, proportion of plaques, and the sdLDL-C, triglycerides (TG) and glucose levels were obviously higher in AIS patients than those in controls. SdLDL-C level in the IMT thickening group was higher than that in the normal IMT group. SdLDL-C and total cholesterol (TC) were risk factors for IMT, while sdLDL-C was an independent risk factor. The IMT value of the unstable plaque group was markedly higher than that of the stable plaque group. The predictive value of IMT for AIS was better than that of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) but not as good as that of sdLDL-C. A logistic regression model was established to predict AIS risk. Additionally, carotid IMT and sdLDL-C were closely related to AIS severity and outcomes. CONCLUSIONS:SdLDL-C and TC were risk factors for increased IMT, while sdLDL-C was an independent risk factor. A prediction model based on IMT and other variables was established to screen the population with high AIS risk.
10.1186/s12944-020-01353-0
Severity of Obstructive Sleep Apnea Is Positively Associated With the Presence of Carotid Artery Atheromas.
Chang Tina I,Lee Urie K,Zeidler Michelle R,Liu Stanley Yung,Polanco John C,Friedlander Arthur H
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons
PURPOSE:Hypoxemia and hypertension caused by obstructive sleep apnea (OSA) often result in atherosclerosis of the carotid and coronary vessels and heightened risk of stroke and myocardial infarction (MI). Therefore, this study investigated whether severity of OSA, based on the apnea-hypopnea index (AHI), is associated with the presence of calcified carotid artery (atherosclerotic) plaque (CCAP) seen on panoramic images (PIs). MATERIALS AND METHODS:Using a cross-sectional study design, the electronic medical records and PIs of all male patients referred from the sleep medicine service to the dental service from 2010 through 2016 were reviewed. The predictor variable was the patients' OSA intensity level as defined by the American Academy of Sleep Medicine based on the AHI score. The outcome variable was the presence of CCAP on the PI. Other variables of interest, that is, demographic and atherogenic risk factors (age, body mass index, diabetes, hypertension, and hyperlipidemia), were included in a multivariate analysis to assess the association of OSA with CCAP. RESULTS:The study sample consisted of 108 men (mean age, 54.7 ± 13.5 yr). Approximately one third (n = 33; 30.6%) presented with CCAP and this group was significantly older with greater odds of co-diagnosis of diabetes (P < .05). Patients with more "severe" OSA showed significantly greater odds of having CCAP on their PIs compared with those with "milder" OSA (odds ratio = 1.035; 95% confidence interval, 1.008-1.062; P = .010) when adjusted for confounders. CONCLUSION:There is a significant association between severity of OSA and the presence of CCAP visible on PI. These atherosclerotic plaques are "risk factors" for stroke and "risk indicators" for future MI; therefore, clinicians providing corrective airway surgery for these patients and noting concomitant CCAP on PI should refer these patients for a thorough cerebrovascular and cardiovascular workup.
10.1016/j.joms.2018.08.004
Association of carotid atherosclerotic plaque and intima-media thickness with the monocyte to high-density lipoprotein cholesterol ratio among low-income residents of rural China: a population-based cross-sectional study.
BMC public health
BACKGROUND:The monocytes to high-density lipoprotein cholesterol ratio (MHR) has been identified as a potential biomarker for cardiovascular and cerebrovascular diseases. In this population-based cross-sectional study, we explored the relationships among carotid artery disease (CAD), including the presence of carotid atherosclerotic plaque (CAP) and carotid artery intima-media thickness (CIMT), the MHR, and related parameter changes. METHODS:This cross-sectional study, Conducted from April to June 2019 in a rural area of Tianjin, involved middle-aged and elderly participants. Based on carotid ultrasound examinations, participants were divided into CAP and non-CAP groups. Logistic regression and Receiver Operating Characteristic (ROC) curve analyses were utilized to assess MHR's predictive value for CAP. Gender-specific analyses were also performed to examine predictive variations. The relationship between CIMT and MHR was evaluated using linear regression. RESULTS:Of the 2109 participants meeting the inclusion criteria, 51.6% were identified with CAP. Multivariate analysis revealed a significant association between MHR and CAP prevalence, (OR, 9.670; 95% CI, 2.359-39.631; P = 0.002), particularly in females (OR, 5.921; 95% CI, 1.823-19.231; P = 0.003), after adjusting for covariates. However, no significant correlation was found between CIMT and MHR when adjusted for other factors. The ROC analysis showed the area under the curve for MHR and CAP to be 0.569 (95% CI: 0.544-0.593; P < 0.001). CONCLUSIONS:These findings suggested that it is crucial to enhance early screening and intervention for CAD, specifically focusing on the prevention and progression of CAP, to address the unique health challenges faced by low-income groups in rural settings. Emphasizing these preventive measures could significantly contribute to improving cardiovascular health outcomes in this vulnerable population.
10.1186/s12889-023-17447-0
Association between cumulative exposure to different lipid parameters and risk of newly developed carotid plaque.
Wu Jianwei,Wang Yu,Kang Kaijiang,Wang Anxin,Xu Jie,Zhao Xingquan
Stroke and vascular neurology
BACKGROUND AND PURPOSE:Both the magnitude and cumulative exposure of atherogenic lipoproteins have an impact on the atherosclerosis risk, and the exploration focus has shifted from one single lipoprotein assessment to the cumulative exposure of lipoproteins. We aim to investigate the relationship between cumulative exposure to different lipid parameters and the risk of newly developed carotid plaque in this study. METHODS:In the Asymptomatic Polyvascular Abnormalities Community study, 2947 participants were included with follow-up every 2 years from 2006 to 2012. Lipid parameters including total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC) and non-HDLC were measured. Cumulative exposure was calculated by adding the weighted sum of the difference between the measured value and the cut-off value of each parameter. Newly developed carotid plaques were identified by carotid ultrasound performed at the third and fourth follow-ups. RESULTS:In the univariate analysis, non-HDLC burden had the highest ORs among the five lipid parameters for newly developed carotid plaque in each quartile, as 1.0 (reference), 1.35 (1.09-1.67), 1.68 (1.36-2.08) and 2.74 (2.22-3.38) from the lowest to the highest quartile. In the multivariate analysis and sensitivity analysis, we obtained similar results. CONCLUSIONS:TC burden, TG burden, LDLC burden and non-HDLC burden are all independent risk factors for newly developed carotid plaque, especially for the vulnerable plaques. Among lipid parameters, non-HDLC burden is an optimal predictor. Moreover, the predictive value remained significant for participants under the age of 65 years old or free of hypertension, diabetes mellitus and hyperlipidaemia.
10.1136/svn-2020-000430
Clinical Parameters and Epigenetic Biomarkers of Plaque Vulnerability in Patients with Carotid Stenosis.
International journal of molecular sciences
Atheromatous disease is the first cause of death and dependency in developed countries and carotid artery atherosclerosis is one of the main causes of severe ischaemic strokes. Current management strategies are mainly based on the degree of stenosis and patient selection has limited accuracy. This information could be complemented by the identification of biomarkers of plaque vulnerability, which would permit patients at greater and lesser risk of stroke to be distinguished, thus enabling a better selection of patients for surgical or intensive medical treatment. Although several circulating protein-based biomarkers with significance for both the diagnosis of carotid artery disease and its prognosis have been identified, at present, none have been clinically implemented. This review focuses especially on the most relevant clinical parameters to take into account in routine clinical practice and summarises the most up-to-date data on epigenetic biomarkers of carotid atherosclerosis and plaque vulnerability.
10.3390/ijms23095149
Normalized wall index, intraplaque hemorrhage and ulceration of carotid plaques correlate with the severity of ischemic stroke.
Cao Xin,Yang Qingluan,Tang Ye,Pan Lei,Lai Mao,Yu Zekuan,Geng Daoying,Zhang Jun
Atherosclerosis
BACKGROUND AND AIMS:Carotid atherosclerosis is considered an important cause of ischemic stroke. Tthis study aimed to explore the relationship between plaque features and the severity of stroke, and to identify plaque risk factors for the assessment of the severity of ischemic stroke. METHODS:Symptomatic patients with carotid atherosclerotic plaques were prospectively recruited and underwent high-resolution vessel wall magnetic resonance imaging (VW-MRI). Two trained MRI readers independently identified intraplaque hemorrhage (IPH), calcification (CA), surface CA, deep CA, and ulceration. They measured and calculated the maximum vessel diameter (Max VD), maximum wall thickness (Max WT), total vessel area, lumen area, normalized wall index (NWI), plaque volume, IPH volume, IPH proportion, CA volume, and CA proportion. Patients were divided into two groups according to their National Institutes of Health Stroke Scale (NIHSS) scores (NIHSS ≤1 vs. NIHSS >1). Clinical characteristics and carotid plaque features were compared using the Mann-Whitney U test or Chi-square test as appropriate. Odds ratio (OR) and corresponding 95% confidence interval (CI) of plaque features to distinguish patients with NIHSS >1 were calculated. Spearman's rank correlations or Pearson correlations were determined for plaque features and NIHSS scores. RESULTS:Of the 97 included patients, 34 (35.05%) with NIHSS >1 had significantly greater NWI (p < 0.05), larger IPH volume (p < 0.01), and greater IPH proportion (p < 0.01), and higher prevalence of IPH (OR, 5.654; 95%CI, 2.272-14.070; p < 0.01) and ulceration (OR, 2.891; 95%CI, 1.090-7.667; p = 0.033) than patients with NIHSS ≤1. Max WT (r = 0.24, p = 0.018), NWI (r = 0.22, p = 0.032), IPH (r = 0.27, p = 0.007), IPH volume (r = 0.35, p < 0.01), IPH proportion (r = 0.28, p = 0.005), and ulceration (r = 0.35, p < 0.01) had positive correlations with NIHSS scores. CONCLUSIONS:NWI, IPH, and ulceration of carotid atherosclerotic plaque based on high-resolution VW-MRI may be useful indicators for assessing the severity of ischemic stroke in patients with atherosclerosis. NIHSS score is related to max WT, NWI, IPH, IPH volume, IPH proportion, and ulceration.
10.1016/j.atherosclerosis.2020.10.896
Differences in left and right carotid plaque vulnerability in patients with bilateral carotid plaques: a CARE-II study.
Stroke and vascular neurology
BACKGROUND AND PURPOSE:Atherosclerosis is a very complex process influenced by various systemic and local factors. Therefore, in patients with bilateral carotid plaques (BCPs), there may be differences in carotid plaque vulnerability between the sides. We aimed to investigate the differences in BCP characteristics in patients with BCPs using magnetic resonance vessel wall imaging (MR-VWI). METHODS:Participants with BCPs were selected for subanalysis from a multicentre study of Chinese Atherosclerosis Risk Evaluation II. We measured carotid plaque burden, identified each plaque component and measured their volume or area bilaterally on MR-VWI. Paired comparisons of the burden and components of BCPs were performed. RESULTS:In all, 540 patients with BCPs were eligible for analysis. Compared with the right carotid artery (CA), larger mean lumen area (p<0.001), larger mean wall area (p=0.025), larger mean total vessel area (p<0.001) and smaller normalised wall index (p=0.006) were found in the left CA. Regarding plaque components, only the prevalence of lipid-rich necrotic core (LRNC) in the left CA was higher (p=0.026). For patients with a vulnerable plaque component coexisting on both sides, only the intraplaque haemorrhage (IPH) volume (p=0.011) was significantly greater in the left CA than in the right CA. CONCLUSIONS:There were asymmetries in plaque growth and evolution between BCPs. The left carotid plaques were more likely to have larger plaque burden, higher prevalence of LRNC and greater IPH volume, which may contribute to the lateralisation of ischaemic stroke in the cerebral hemispheres.
10.1136/svn-2022-001937
Long-term trajectories of BMI predict carotid stiffness and plaque volume in type 2 diabetes older adults: a cohort study.
Cardiovascular diabetology
BACKGROUND:High body mass index (BMI) is a risk factor for type 2 diabetes and cardiovascular disease. However, its relationships with indices of carotid stiffness and plaque volume are unclear. We investigated associations of long-term measurements of BMI with indices of carotid stiffness and atherosclerosis among non-demented diabetes patients from the Israel Diabetes and Cognitive Decline (IDCD) study. METHODS:Carotid ultrasound indices [carotid intima media thickness (cIMT), distensibility, elastography and plaque volume] were assessed in N = 471 participants. Mean BMI across all MHS diabetes registry measurements and trajectories of BMI were calculated. BMI was categorized into three trajectory groups representing: a relatively stable normal weight (n = 185, 44%), overweight trajectory (n = 188, 44.8%) and a trajectory of obesity (n = 47, 11.2%). Linear and logistic regressions estimated associations of carotid indices with mean BMI and BMI trajectories. RESULTS:Compared to the normal weight trajectory, an obesity trajectory was associated with carotid distensibility (β = - 3.078, p = 0.037), cIMT (β = 0.095, p = 0.004), and carotid elastography (β = 0.181, p = 0.004) but not with plaque volume (β = 0.066, p = 0.858). Compared with the normal weight trajectory, an obesity trajectory was associated with increased odds for impaired carotid distensibility (OR = 2.790, p = 0.033), impaired cIMT (OR = 5.277, p = 0.001) and large carotid plaque volume (OR = 8.456, p = 0.013) but not with carotid elastography (OR = 1.956, p = 0.140). Mean BMI was linearly associated with Distensibility (β = - 0.275, p = 0.005) and cIMT (β = 0.005, p = 0.026). CONCLUSIONS:Long-term measurements of adiposity are associated with indices of carotid stiffness and plaque volume among older type 2 diabetes adults.
10.1186/s12933-020-01104-6
Atherosclerotic plaque locations may be related to different ischemic lesion patterns.
Woo Ho Geol,Heo Sung Hyuk,Kim Eui Jong,Chang Dae-Il,Song Tae Jin,Kim Bum Joon
BMC neurology
BACKGROUND:Atherosclerosis of the internal carotid artery (ICA) is an important cause of ischemic stroke. Artery-to-artery embolism is the major stroke mechanism in patients with atherosclerotic carotid disease. This study hypothesized that the atherosclerotic ICA geometry and plaque location would be associated with lesion pattern in patients with acute ischemic stroke. METHODS:Ischemic stroke patients with symptomatic proximal ICA disease (> 50% diameter stenosis) were enrolled. The carotid plaque location was divided into high-apical and low-body types. The geometric parameters of the ICA (angles between arteries) were measured, and ischemic lesion patterns were classified according to the number, location, and size of the lesions. Factors associated with plaque location and lesion pattern, dichotomized by size, were investigated. RESULTS:Of the 93 acute ischemic stroke patients enrolled, 31 had high-apical and 62 had low-body plaques. Hyperlipidemia was more prevalent and the common carotid artery (CCA)-ICA angle was wider (167.7 ± 10.4° vs 162.3 ± 9.8°, p = 0.019) in patients with low-body than high-apical plaques. Low-body plaques were more frequently associated with small scattered or cortical lesions (54.8% vs. 32.3%, p = 0.040), whereas high-apical plaques were more frequently associated with large lesions having additional lesions (38.7% vs. 11.3%, p = 0.002). The presence of low-body plaques (odds ratio: 3.106, 95% confidence interval: 1.105-8.728, p = 0.032) was independently associated with the small lesion-only pattern. CONCLUSIONS:Low-body plaques are more frequently associated with small scattered lesions, whereas high-apical plaques are more frequently associated with large lesions having additional lesions. A wide CCA-ICA angle is associated with low-body plaque of the carotid artery.
10.1186/s12883-020-01868-0
Prevalence and characteristics of atherosclerotic plaque: Left compared with right arteries and anterior compared with posterior circulation stroke.
Cai Yan,Liu Xiaoshuang,Zhang Lijuan,Guo Haoming,Gong Qihui,Lv Fajin
European journal of radiology
PURPOSE:To evaluate atherosclerotic plaque prevalence and characteristics between left and right cervicocephalic arteries and between anterior and posterior circulation stroke (ACS and PCS). METHODS:This retrospective study included 284 patients with acute ischemic stroke (199 ACS and 85 PCS) involving large-artery atherosclerosis or small-artery occlusion. We assessed atherosclerotic plaque prevalence and characteristics (plaque type, plaque surface morphology, plaque distribution, location of calcified nodules and plaque thickness) in each segment and their comparisons between left and right arteries and between ACS and PCS. RESULTS:The left subclavian artery (L-SA), common carotid artery (L-CCA) and intracranial vertebral artery (L-IVA) had significantly higher prevalence of atherosclerotic plaque than the right (R) corresponding arteries (70.1% versus 59.5%, P = 0.008), (48.1% versus 28.9%, P < 0.001), (23.9% versus 16%, P = 0.018), respectively. L-SA had a higher prevalence of mixed plaque (non-calcified > calcified) (19.6% versus 16.4%) and noncalcified plaque (51.9% versus 31.7%), and a lower prevalence of calcified plaque (8.9% versus 23.3%) and mixed plaque (calcified > non-calcified) (19.6% versus 28.6%) than R-SA, P < 0.001. The distribution of plaque type in the SA and extracranial vertebral artery (EVA) were significantly different between ACS and PCS. The soft plaque thickness of SA in PCS was significantly greater than that in ACS (3.85 ± 1.27 versus 3.51 ± 1.04, P = 0.032). CONCLUSIONS:Atherosclerotic plaque prevalence and characteristics vary in different segments, sides and between ACS and PCS. These differences should be noted during plaque diagnosis.
10.1016/j.ejrad.2021.109862
Search for Reliable Circulating Biomarkers to Predict Carotid Plaque Vulnerability.
Puig Núria,Jiménez-Xarrié Elena,Camps-Renom Pol,Benitez Sonia
International journal of molecular sciences
Atherosclerosis is responsible for 20% of ischemic strokes, and the plaques from the internal carotid artery the most frequently involved. Lipoproteins play a key role in carotid atherosclerosis since lipid accumulation contributes to plaque progression and chronic inflammation, both factors leading to plaque vulnerability. Carotid revascularization to prevent future vascular events is reasonable in some patients with high-grade carotid stenosis. However, the degree of stenosis alone is not sufficient to decide upon the best clinical management in some situations. In this context, it is essential to further characterize plaque vulnerability, according to specific characteristics (lipid-rich core, fibrous cap thinning, intraplaque hemorrhage). Although these features can be partly detected by imaging techniques, identifying carotid plaque vulnerability is still challenging. Therefore, the study of circulating biomarkers could provide adjunctive criteria to predict the risk of atherothrombotic stroke. In this regard, several molecules have been found altered, but reliable biomarkers have not been clearly established yet. The current review discusses the concept of vulnerable carotid plaque, and collects existing information about putative circulating biomarkers, being particularly focused on lipid-related and inflammatory molecules.
10.3390/ijms21218236
Association of carotid wall layers with atherosclerotic plaques and cardiac hypertrophy in hypertensive subjects.
Journal of human hypertension
Carotid intima-media thickness (cIMT) is considered a marker of subclinical atherosclerosis and is related to target-organ damage in hypertensive patients. However, increased cIMT may be due to increases in the thickness of intima (cIT) and media (cMT) layers. This study evaluated whether cIMT layers (cIT and cMT) had a greater association with carotid atherosclerotic plaques and left ventricular hypertrophy (LVH) than cIMT in hypertensive subjects. We cross-sectionally evaluated clinical, carotid, and echocardiography characteristics of 186 hypertensive patients followed at an outpatient clinic. High-resolution images of common carotid arteries were obtained by ultrasonography equipped with 10-MHz transducers, and cIT, cMT, and cIMT were manually measured using an image-processing software. Among all participants (n = 186; age = 60.8 ± 10.9 years, 43% males), there were 58% with carotid plaques and 58% with LVH. Mean cIT, cMT, and cIMT values were 0.267 ± 0.060, 0.475 ± 0.107, and 0.742 ± 0.142 mm, respectively. In logistic regression analysis adjusted for relevant covariates, carotid plaques showed stronger association with cIT than with cMT and cIMT. Furthermore, cIT showed greater area under the ROC curve (0.92; 95% CI 0.87-0.96) than cIMT (0.79; 95% CI 0.72-0.85) and cMT (0.64; 95% CI 0.56-0.72) to identify plaques. Conversely, cIT, cMT, and cIMT had modest association and accuracy to identify LVH (area under the ROC curve = 0.61, 0.57, and 0.60, respectively). In conclusion, cIT is a more accurate marker of atherosclerosis than cMT or cIMT, while cIT and cMT provide no incremental value in identifying LVH when compared with cIMT among hypertensive subjects.
10.1038/s41371-021-00565-w
Carotid Plaque Vulnerability Assessed by Combined Shear Wave Elastography and Ultrafast Doppler Compared to Histology.
Translational stroke research
Ultrafast ultrasound imaging (UUI) provides an estimation of carotid plaque stiffness by shear wave elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed to evaluate the combined criteria of plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability assessed by histology. We included patients for whom carotid endarterectomy had been decided by a multidisciplinary team. UUI was performed within 48 h before surgery, and acquisitions were obtained on a carotid longitudinal view. After endarterectomy, gross examination and histological analysis were performed on each removed plaque. Forty-six plaques with SWE data and 29 with WSS data were analyzed. Histological analysis revealed 29 vulnerable and 17 stable plaques. Gray-scale median analysis by B-mode, mean, and standard deviation of stiffness by SWE did not differ between vulnerable and stable plaques. SWE analysis revealed that the percentage of stiffness range of 3-5 m/s was significantly increased in vulnerable plaques (p = 0.048). WSS alone showed no difference between stable and vulnerable plaques regardless of the segment of the plaque which was analyzed. A multiparametric score using maximal WSS at the peak of the plaque associated with SWE texture analysis parameters was calculated by stepwise regression, leading to a score with a sensitivity of 80% and a specificity of 78%. Area under the receiver operating characteristics curve was 0.85. A multiparameter scoring system including plaque stiffness and flow analysis using UUI allows to effectively identify histologically vulnerable carotid plaques. ClinicalTrials.gov Identifier: NCT03234257.
10.1007/s12975-021-00920-6
Association between lipid profiles and presence of carotid plaque.
Liu Yanhua,Zhu Yongjian,Jia Wenrui,Sun Dan,Zhao Li,Zhang Chen,Wang Cuicui,Chen Gaiyun,Fu Sanxian,Bo Yacong,Xing Yurong
Scientific reports
It is indicated that lipids profiles are associated with carotid plaque and Atherosclerosis. However, studies about the relationship between serum lipid profiles and carotid plaque composition in Chinese Population is limited. We conducted a cross-sectional study among 3,214 participants between January 2015 and December 2017 in China, to investigate the association between various lipid profiles and the prevalence of carotid plaque. Logistic regression model was used to investigate the association between plasma lipid profiles and odds of carotid plaque. Analysis of covariance (ANCOVA) was used to compare the mean plasma lipid profiles among different number and composition of carotid artery plaques. HDL-C, Non-HDL-C levels, TC/HDL-C, LDL-C/HDL-C were significantly associated with the presence of carotid plaque; HDL-C, LDL-C, Non-HDL-C levels, TC/HDL-C, LDL-C/HDL-C were significantly associated with the presence of common carotid artery (CCA) plaque. Compare with participants without carotid plaque, increased level of LDL-C/HDL-C was found in those with echolucent/polytype plaque. Similarly, compared with participants without CCA plaque, increased level of LDL-C/HDL-C was found in those with echolucent plaque. In conclusion, we found that serum HDL-C, Non-HDLc level, TC/HDLc, and LDLc/HDLc were all associated with the prevalence of carotid plaque, and LDL-C/HDL-C differed among different group of carotid plaque composition.
10.1038/s41598-019-54285-w
Contribution of atherosclerotic plaque location and severity to the near-wall hemodynamics of the carotid bifurcation: an experimental study and FSI modeling.
Ahmadpour-B Mahyar,Nooraeen Ahmad,Tafazzoli-Shadpour Mohammad,Taghizadeh Hadi
Biomechanics and modeling in mechanobiology
Atherosclerosis is initiated by endothelial injury that is related to abnormal values of hemodynamic parameters such as wall shear stress (WSS), oscillatory shear index (OSI) and stress phase angle (SPA), which are more common in arterial bifurcations due to the complex structure. An experimental model of human carotid bifurcation with accurate geometrical and mechanical features was set up, and using realistic pulsatile flow rates, the inlet and outlet pressure pulses were measured for normal and stenosed models with 40% and 80% severities at common carotid (CCA), internal carotid (ICA) and external carotid (ECA) arteries. Based on the obtained experimental data, fluid-structure models were developed to obtain WSS, OSI, and SPA and evaluate pathological consequences at different locations. Mild severity had minor impact, however, inducing severe 80% stenosis in each branch led to considerable localized changes of hemodynamic parameters both in the stenosis site and other locations. This included sharp increases in WSS values accompanied by very low values close to zero before and after the peaks. Severe stenosis not only caused significant changes in the local artery, but also in other branches. OSI and SPA were less sensitive to stenosis, although high peaks were observed on bifurcation site for the stenosis at ECA. The interconnection of arteries at carotid bifurcation results in altered pressure/flow patterns in all branches when a stenosis is applied in any site. Such effect confirms pathological findings that atherosclerotic plaques are observed simultaneously in different carotid branches, although with different degrees of plaque growth and severity.
10.1007/s10237-021-01431-x
Complicated Carotid Artery Plaques and Risk of Recurrent Ischemic Stroke or TIA.
Journal of the American College of Cardiology
BACKGROUND:Complicated nonstenosing carotid artery plaques (CAPs) are an under-recognized cause of stroke. OBJECTIVES:The purpose of this study was to determine whether complicated CAP ipsilateral to acute ischemic anterior circulation stroke (icCAP) are associated with recurrent ischemic stroke or transient ischemic attack (TIA). METHODS:The CAPIAS (Carotid Plaque Imaging in Acute Stroke) multicenter study prospectively recruited patients with ischemic stroke restricted to the territory of a single carotid artery. Complicated (AHA-lesion type VI) CAP were defined by multisequence, contrast-enhanced carotid magnetic resonance imaging obtained within 10 days from stroke onset. Recurrent events were assessed after 3, 12, 24, and 36 months. The primary outcome was recurrent ischemic stroke or TIA. RESULTS:Among 196 patients enrolled, 104 patients had cryptogenic stroke and nonstenosing CAP. During a mean follow-up of 30 months, recurrent ischemic stroke or TIA occurred in 21 patients. Recurrent events were significantly more frequent in patients with icCAP than in patients without icCAP, both in the overall cohort (incidence rate [3-year interval]: 9.50 vs 3.61 per 100 patient-years; P = 0.025, log-rank test) and in patients with cryptogenic stroke (10.92 vs 1.82 per 100 patient-years; P = 0.003). The results were driven by ipsilateral events. A ruptured fibrous cap (HR: 4.91; 95% CI: 1.31-18.45; P = 0.018) and intraplaque hemorrhage (HR: 4.37; 95% CI: 1.20-15.97; P = 0.026) were associated with a significantly increased risk of recurrent events in patients with cryptogenic stroke. CONCLUSIONS:Complicated CAP ipsilateral to acute ischemic anterior circulation stroke are associated with an increased risk of recurrent ischemic stroke or TIA. Carotid plaque imaging identifies high-risk patients who might be suited for inclusion into future secondary prevention trials. (Carotid Plaque Imaging in Acute Stroke [CAPIAS]; NCT01284933).
10.1016/j.jacc.2022.03.376
Systemic immune-inflammation index is associated with ulcerative plaque in patients with acute ischemic stroke: A single center exploratory study.
Journal of clinical ultrasound : JCU
PURPOSE:This study explored the correlation between inflammatory markers and ulcerative plaques based on carotid doppler ultrasound (CDU) in individuals with acute ischemic stroke (AIS). METHODS:A total of 202 cases diagnosed with AIS associated with atherosclerotic plaque (AP) in the carotid artery were enrolled in this research. Collecting clinical baseline data, laboratory data (such as the complete blood count) and imaging data (CDU and Brain magnetic resonance imaging [MRI]). Then the correlation between Systemic immune-inflammation index (SII, SII = P N/L, where P, N, and L were the peripheral blood platelet, neutrophil and lymphocyte counts, respectively), the shape and position of AP, the degree of carotid artery stenosis, and the presence of ulcerative plaques. Cutoff values were determined accordingly. RESULTS:SII and high sensitivity CRP (hs-CRP) were independent risk factors for the presence of vulnerable carotid plaques. SII, type A plaque, plaque above carotid bifurcation, and severe carotid stenosis were independent risk factors for the presence of ulcerative plaque. The AUC value, the sensitivity, specificity, the best cutoff value of SII in predicting the presence of ulcerative plaque was 0.895, 93.3%, 89.2%, and 537.4 (10 /L), respectively. CONCLUSION:SII at admission was found to be independently associated with the presence of AIS with vulnerable plaque, especially ulcerative plaques. Moreover, plaque ulceration was more likely to form when the area of higher plaque thickness was located in the upstream arterial wall of maximum plaque thickness (WTmax), plaque was above the carotid bifurcation and severe carotid stenosis.
10.1002/jcu.23632
Comparison of the Predictive Value of Inflammatory Biomarkers for the Risk of Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke.
Clinical interventions in aging
Purpose:To investigate the predictive value of various inflammatory biomarkers in patients with acute ischemic stroke (AIS) and evaluate the relationship between stroke-associated pneumonia (SAP) and the best predictive index. Patients and Methods:We calculated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), prognostic nutritional index (PNI), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and prognostic index (PI). Variables were selectively included in the logistic regression analysis to explore the associations of NLR, PLR, MLR, PNI, SIRI, SII, GPS, mGPS, and PI with SAP. We assessed the predictive performance of biomarkers by analyzing receiver operating characteristic (ROC) curves. We further used restricted cubic splines (RCS) to investigate the association. Next, we conducted subgroup analyses to investigate whether specific populations were more susceptible to NLR. Results:NLR, PLR, MLR, SIRI, SII, GPS, mGPS, and PI increased significantly in SAP patients, and PNI was significantly decreased. After adjustment for potential confounders, the association of inflammatory biomarkers with SAP persisted. NLR showed the most favorable discriminative performance and was an independent risk factor predicting SAP. The RCS showed an increasing nonlinear trend of SAP risk with increasing NLR. The AUC of the combined indicator of NLR and C-reactive protein (CRP) was significantly higher than those of NLR and CRP alone (DeLong test, <0.001). Subgroup analyses suggested good generalizability of the predictive effect. Conclusion:NLR, PLR, MLR, PNI, SIRI, SII, GPS, mGPS, and PI can predict the occurrence of SAP. Among the indices, the NLR was the best predictor of SAP occurrence. It can therefore be used for the early identification of SAP.
10.2147/CIA.S425393
Correlation between Immune-Inflammatory Markers and Clinical Features in Patients with Acute Ischemic Stroke.
Chu Yu-Wei,Chen Pei-Ya,Lin Shinn-Kuang
Acta neurologica Taiwanica
OBJECTIVE:Chronic inflammatory processes involving the vascular wall may induce atherosclerosis. Immune-inflammatory processes proceed throughout all stages of acute stroke. We investigated the association of three immune-inflammatory markers, namely systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and neutrophil count (NC), with prehospital delay and clinical features in patients with acute ischemic stroke. METHODS:We retrospectively enrolled 2543 inpatients admitted within 4 days of symptom onset from May 2010 to February 2020. Patients were stratified into three groups: Group A, comprising 161 patients with tissue plasminogen activator (tPA) treatment; Group B, comprising 415 patients who were eligible for tPA treatment; and Group C, comprising all 2543 patients. RESULTS:The levels of all three immune-inflammatory markers had positive linear correlations with onsetto- emergency room time, initial National Institutes of Health Stroke Scale (NIHSS) scores, and discharge modified Rankin Scale scores. In Group B, levels of follow-up, but not initial, immuneinflammatory markers were higher in patients with unfavorable outcomes. Common significant predictors of in-hospital complications and unfavorable outcomes were age > 72 years, female sex, NIHSS > 4, diabetes mellitus, and all three immune-inflammatory markers. When combined with other predictors, NC > 7.2 × 103/mL achieved optimal predictive performance (0.794) for in-hospital complications, and SII > 651, NLR > 2.9, and NC > 7.2 × 103/mL had equal predictive performance up to 0.859 for unfavorable outcomes. CONCLUSIONS:Immune-inflammatory markers dynamically increased from symptom onset of acute ischemic stroke in patients eligible for thrombolytic therapy. Higher levels of immune-inflammatory markers suggest more in-hospital complications and unfavorable short-term outcomes.
Increased Systemic Immune-Inflammation Index Predicts Disease Severity and Functional Outcome in Acute Ischemic Stroke Patients.
The neurologist
BACKGROUND:Systemic immune-inflammation index (SII) and system inflammation response index (SIRI) have been recently investigated as novel inflammatory and prognostic markers. Our study aimed to investigate the relationship between SII and SIRI index and severity of stroke, and to analyze the prognostic value in acute ischemic stroke (AIS) patients. METHODS:The SII is defined as platelet×(neutrophil count/lymphocyte count), SIRI is defined as neutrophil count×(monocyte count/lymphocyte count). We plotted receiver operating characteristic curves of SII and SIRI for poor outcomes and calculated area under the curve (AUC) values and cutoff values. Multivariate logistic regression analysis was performed to analyze the association between SII/SIRI index and poor functional outcome. RESULTS:We included 234 AIS patients [mean age 69 (57-78) years; 50.4% male]. Both SII and SIRI were higher in the moderate-to-severe stroke group than in the mild stroke group [932.73 (569.84-1610.90) vs. 581.21 (386.98-1015.59), P <0.001 and 2.00 (1.24-3.13) vs. 1.35 (0.83-1.92), P <0.001]. The area under the receiver operating characteristic curve (area under the curve) value of SII (0.678, 0.608-0.748, P <0.001) tested a similar discriminatory ability compared with SIRI (0.682, 95% CI (0.612-0.751), P <0.001). Multivariate logistic regression analyses showed that SII was significantly associated with poor prognosis at discharge of AIS patients [adjusted odds ratio (95% confidence interval): 2.350 (1.149-4.803), P =0.019)], conversely, SIRI had no prognostic value. CONCLUSIONS:Higher SII and SIRI indexes were correlated with greater risk of stroke severity, meanwhile SII could be useful for predicting adverse clinical outcomes after AIS.
10.1097/NRL.0000000000000464
Systemic Immune-Inflammation Index Predicts Tumor Recurrence after Radical Resection for Colorectal Cancer.
The Tohoku journal of experimental medicine
The systemic inflammatory response is associated with tumor promotion and suppression. Accumulating evidence shows that peripheral blood markers of inflammatory response predict clinical outcomes in various human cancers. The aim of this study was to investigate the prognostic relevance of the inflammation-based biomarkers in colorectal cancer (CRC). We retrospectively analyzed 118 CRC patients who underwent curative resection between 2012 and 2017. The inflammation-based biomarkers were evaluated by using preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), prognostic nutritional index (PNI), and Glasgow prognostic score (GPS). Prognostic values were assessed by the Kaplan-Meier analysis for cancer-specific recurrence-free survival (RFS) and Cox proportional-hazards model. There were significant differences in the levels of NLR, PLR, SII, and SIRI between recurrence and non-recurrence group. The area under the curve (AUC) for SII was 0.710, which showed the highest value in the inflammation-based biomarkers. Multivariate analysis identified that SII (p = 0.0031) and lymph node metastasis (p = 0.0168) were independent prognostic factors for recurrence. High SII exhibited more dismal RFS than low SII in CRC patients with non-metastatic lymph node (p = 0.0002). Our study suggests that SII and lymph node metastasis could be useful indicators in predicting the recurrence of CRC patients. Additionally, SII could accurately stratify CRC patients with tumor recurrence by combining with lymph node metastasis. This result would be beneficial for determining the optimal therapeutic strategies after surgical resection for CRC.
10.1620/tjem.2023.J074
Association between systemic immune-inflammation index and metabolic syndrome and its components: results from the National Health and Nutrition Examination Survey 2011-2016.
Journal of translational medicine
BACKGROUND:Metabolic syndrome (MetS), a worldwide public health problem, affects human health and quality of life in a dramatic manner. A growing evidence base suggests that MetS is strongly associated with levels of systemic immune inflammation. The present study aimed to investigate the possible relationship between the systemic immune-inflammation index (SII), a novel inflammatory marker, and MetS to provide data support for effective MetS prevention by reducing the systemic inflammatory response. METHODS:We included adult participants with complete SII and MetS information from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). MetS was defined as using the criteria developed by the Adult Treatment Program III of the National Cholesterol Education Program. The formula for SII was as follows: SII = platelet counts × neutrophil counts/ lymphocyte counts. Weighted linear regression was used to assess differences in variables across SII quartile groups after the SII score was divided into 4 quartiles. The independent interaction between SII and MetS was investigated using weighted multivariate logistic regression analysis and subgroup analysis, and the relationship between SII levels and 5 particular MetS items was further explored in depth. RESULTS:A total of 12,402 participants, 3,489 of whom were diagnosed with MetS, were included in this study. After correcting for covariates, the results of a logistic regression of multistage weighted complex sampling data revealed that participants with higher SII scores had a higher chance of developing MetS (odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.14-1.55) and that SII levels could be used as an independent risk factor to predict that likelihood of MetS onset. In the Q1-Q4 SII quartile group, the risk of developing MetS was 1.33 times higher in the Q4 group, which had the highest level of systemic immune inflammation than in the Q1 group. After adjusting for all confounding factors, SII scores were found to have a negative correlation with high-density lipoprotein cholesterol (OR = 1.29; 95% CI, 0.99-1.67, P = 0.056) and a significant positive correlation with waist circumference (OR = 2.17; 95% CI, 1.65-2.87, P < 0.001) and blood pressure (BP) (OR = 1.65; 95% CI, 1.20-2.27, P = 0.003). Gender, age, and smoking status were shown to alter the positive association between SII and MetS in subgroup analyses and interaction tests (p for interaction < 0.05). Additionally, we demonstrated a nonlinear correlation between SII and MetS. The findings of the restricted cubic spline indicated that there was an inverted U-shaped association between SII and MetS. CONCLUSIONS:Our findings imply that increased SII levels are related to MetS, and SII may be a simple and cost-effective method to identify individuals with MetS. Therefore, protective measures such as early investigation and anti-inflammatory interventions are necessary to reduce the overall incidence of MetS.
10.1186/s12967-023-04491-y
Clopidogrel increases risk of pneumonia compared with aspirin in acute ischemic minor stroke patients.
Yu Zhangfeng,Zhou Hua,Shan Baoshuai,Fu Jianzhong,Zhu Hao,Feng Qian,Shen Rong,Jin Xing
Journal of thrombosis and thrombolysis
Antiplatelet agents may increase the risk of infections via suppressing platelet-mediated immune response. Here we assessed the contribution of clopidogrel versus aspirin to the development of pneumonia during an acute ischemic stroke admission. A retrospective cohort study was conducted of acute ischemic stroke patients who were admitted to our hospital from 2015 to 2018. Included patients received uninterrupted clopidogrel or aspirin therapy and did not take other antiplatelet agents throughout their stay. The interest outcome was development of pneumonia after stroke. Conditional logistic regression model after propensity score matching and adjusted logistic regression model were used to assess the impact of clopidogrel versus aspirin on post-stroke pneumonia. Among 1470 included patients, 1135 received aspirin and 335 received clopidogrel. Total 149 patients (10.1%) experienced pneumonia during the stroke hospitalization period. No difference was observed between clopidogrel cohort and aspirin cohort in the incidence of post-stroke pneumonia after propensity score matching (relative risk, 1.04; 95% confidence interval (CI) 0.65-1.65; P = 0.875). However, we found that clopidogrel was associated with increased risk of pneumonia compared with aspirin in minor stroke patients (adjusted odds ratio, 2.21; 95% CI 1.12-4.34; P = 0.021), and a statistically insignificant increase of pneumonia in diabetics (adjusted odds ratio, 1.94; 95% CI 0.96-3.94; P = 0.065). Compared with aspirin, clopidogrel is associated with increased pneumonia in minor stroke patients among who the interference of stroke-induced immunosuppression is minimized. Hence, aspirin may be a better choice for minor stroke patients in acute phase of ischemic stroke when pneumonia most frequently occurs.
10.1007/s11239-020-02306-1
Dual versus mono antiplatelet therapy in mild-to-moderate stroke during hospitalization.
Annals of clinical and translational neurology
OBJECTIVE:Subsequent vascular events are common after acute ischemic stroke during hospitalization. This study aimed to analyze the effectiveness of combination therapy with clopidogrel and aspirin among mild-to-moderate ischemic stroke patients treated within 72 h on the basis of a high-intensity dose of statins. METHODS:In a retrospective and multicenter cohort study, acute (within 72 h of onset) mild-to-moderate stroke patients were divided into aspirin and clopidogrel-aspirin groups on the basis of a high-intensity dose of statin therapy. The primary outcome was compound vascular events during hospitalization. Cox's proportional hazards model was used to assess differences, with the study center as a random effect. RESULTS:Among the 506 patients meeting the eligibility criteria, all subjects received a high-intensity dose of statins, including 20 mg rosuvastatin or 40 mg atorvastatin while in the hospital. In an unadjusted analysis, compound vascular events occurred in 7.2% of patients in the clopidogrel-aspirin group compared with 13.7% of those in the aspirin group (p = 0.022). In a Cox proportional hazards regression analysis, clopidogrel-aspirin was associated with a lower risk of compound vascular events (hazard ratio [95% CI], 0.47 [0.25-0.87]; p = 0.017) and ischemic vascular events (p = 0.008). Moderate and severe hemorrhage occurred in four patients (1.07%) in the clopidogrel-aspirin group and three patients (2.30%) in the aspirin group (p = 0.626). INTERPRETATION:In this study based on high-intensity statin therapy, clopidogrel-aspirin reduced the risk of compound vascular events and did not increase the risk of hemorrhage during patients' hospitalization after mild-to-moderate ischemic stroke within 72 h.
10.1002/acn3.51541
Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.
Stroke
BACKGROUND:Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS:In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS:From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS:Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.
10.1161/STROKEAHA.123.043769
Comparative Effectiveness of Dual Antiplatelet Therapy With Aspirin and Clopidogrel Versus Aspirin Monotherapy in Mild-to-Moderate Acute Ischemic Stroke According to the Risk of Recurrent Stroke: An Analysis of 15 000 Patients From a Nationwide, Multicenter Registry.
Lee Hak-Loh,Kim Joon-Tae,Lee Ji Sung,Park Man-Seok,Choi Kang-Ho,Cho Ki-Hyun,Kim Beom Joon,Park Jong-Moo,Kang Kyusik,Lee Soo Joo,Kim Jae Guk,Cha Jae-Kwan,Kim Dae-Hyun,Park Tai Hwan,Park Sang-Soon,Lee Kyung Bok,Lee Jun,Hong Keun-Sik,Cho Yong-Jin,Park Hong-Kyun,Lee Byung-Chul,Yu Kyung-Ho,Sun Oh Mi,Kim Dong-Eog,Ryu Wi-Sun,Choi Jay Chol,Kwon Jee-Hyun,Kim Wook-Joo,Shin Dong-Ick,Sohn Sung Il,Hong Jeong-Ho,Lee Juneyoung,Bae Hee-Joon
Circulation. Cardiovascular quality and outcomes
BACKGROUND:This study compared the effectiveness of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin with that of aspirin monotherapy (AM) in mild-to-moderate acute ischemic stroke considering the risk of recurrent stroke using the Stroke Prognosis Instrument II (SPI-II) score. METHODS:This study is a retrospective analysis of data from a prospective, nationwide, multicenter stroke registry database between January 2011 and July 2018. We included patients with mild-to-moderate (National Institutes of Health Stroke Scale score ≤10), acute (within 24 hours of onset), noncardioembolic ischemic stroke. The primary outcome was a 3-month composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause mortality. Propensity scores using the inverse probability of treatment weighting method were used to mitigate baseline imbalances between the DAPT and AM groups and within each subgroup considering SPI-II scores. RESULTS:Among the 15 430 patients (age, 66±13 years; men, 62.0%), 45.1% (n=6960) received DAPT and 54.9% (n=8470) received AM. Primary outcome events were significantly more frequent in the AM group (16.7%) than in the DAPT group (15.5%; =0.03). Weighted Cox proportional hazards models showed a reduced risk of 3-month primary vascular events in the DAPT group versus the AM group (hazard ratio, 0.84 [0.78-0.92]; <0.001), with no interaction between acute treatment type and SPI-II risk subgroups (=0.44). However, among the high-risk patients with SPI-II scores >7, a substantially larger absolute benefit was observed for 3-month composite vascular events in the DAPT group (weighted absolute risk differences, 5.4%), whereas smaller absolute benefits were observed among patients in the low- or medium-risk SPI-II subgroups (1.7% and 2.4%, respectively). CONCLUSIONS:Treatment with clopidogrel-aspirin was associated with a reduction in 3-month vascular events compared with AM in mild-to-moderate acute noncardioembolic ischemic stroke patients. Larger magnitudes of the effects of DAPT with clopidogrel-aspirin were observed in the high-risk subgroup by SPI-II risk scores.
10.1161/CIRCOUTCOMES.119.006474
The effect of clopidogrel and aspirin on the severity of traumatic brain injury in a rat model.
Kobeissy Firas,Mallah Khalil,Zibara Kazem,Dakroub Fatima,Dalloul Zeinab,Nasser Mohammad,Nasrallah Leila,Mallah Zahraa,El-Achkar Ghewa A,Ramadan Naify,Mohamed Wael,Mondello Stefania,Darwish Hala,Hamade Eva,Habib Aida
Neurochemistry international
Traumatic Brain Injury (TBI) is one of the leading causes of death and disability worldwide. Aspirin (ASA) and clopidogrel (CLOP) are antiplatelet agents that inhibit platelet aggregation. They are implicated in worsening the intracerebral haemorrhage (ICH) risk post-TBI. However, antiplatelet drugs may also exert a neuroprotective effect post-injury. We determined the impact of ASA and CLOP treatment, alone or in combination, on ICH and brain damage in an experimental rat TBI model. We assessed changes in platelet aggregation and measured serum thromboxane by enzyme immune assay. We also explored a panel of brain damage and apoptosis biomarkers by immunoblotting. Rats were treated with ASA and/or CLOP for 48 h prior to TBI and sacrificed 48 h post-injury. In rats treated with antiplatelet agents prior to TBI, platelet aggregation was completely inhibited, and serum thromboxane was significantly decreased, compared to the TBI group without treatment. TBI increases UCHL-1 and GFAP, but decreases hexokinase expression compared to the non-injured controls. All groups treated with antiplatelet drugs prior to TBI had decreased UCH-L1 and GFAP serum levels compared to the TBI untreated group. Furthermore, the ASA and CLOP single treatments increased the hexokinase serum levels. We confirmed that αII-spectrin cleavage increased post-TBI, with the highest cleavage detected in CLOP-treated rats. Aspirin and/or CLOP treatment prior to TBI is a double-edged sword that exerts a dual effect post-injury. On one hand, ASA and CLOP single treatments increase the post-TBI ICH risk, with a further detrimental effect from the ASA + CLOP treatment. On the other hand, ASA and/or CLOP treatments are neuroprotective and result in a favourable profile of TBI injury markers. The ICH risk and the neuroprotection benefits from antiplatelet therapy should be weighed against each other to ameliorate the management of TBI patients.
10.1016/j.neuint.2022.105301
The safety and effectiveness of clopidogrel versus aspirin in Kawasaki disease with mild-to-moderate liver injury.
Scientific reports
Kawasaki disease can be combined with liver injury. As a mainstay treatment for Kawasaki disease, aspirin may cause liver injury. This study aimed to compare the safety and effectiveness of clopidogrel versus aspirin in Kawasaki disease with mild-to-moderate liver injury. This study retrospectively analysed 166 children with Kawasaki disease combined with mild-to-moderate liver injury. The children treated with clopidogrel were less likely to have aggravated liver injury than those treated with aspirin (n = 2/100 vs. n = 13/66, P < 0.001). The initial alanine aminotransferase value of the clopidogrel group was higher (131.5 [98.5, 167.5] vs. 96 [72, 133], P < 0.001), while the time of alanine aminotransferase recovery to normal was similar (5 [4, 7] vs. 4 [3, 7], P = 0.179). No significant fever differences observed between groups: 7.5 [6, 9] for aspirin vs. 7 [6, 8] for clopidogrel group, P = 0.064. The probability of nonresponse to intravenous immunoglobulin (n = 29/100 vs. n = 30/66, P = 0.030) and the days of hospitalization (n = 6 [4, 9] vs. n = 7 [5, 10], P = 0.007) in the clopidogrel group were less than those in the aspirin group. In conclusion, the application of clopidogrel is potentially superior to aspirin in Kawasaki disease combined with mild-to-moderate liver injury.
10.1038/s41598-023-45647-6
Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.
JAMA neurology
Importance:Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective:To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants:This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions:Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures:The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results:Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance:Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration:ClinicalTrials.gov Identifier: NCT02869009.
10.1001/jamaneurol.2024.0146
Impact of hemoglobin levels at admission on outcomes among elderly patients with acute coronary syndrome treated with low-dose Prasugrel or clopidogrel: A sub-study of the ELDERLY ACS 2 trial.
International journal of cardiology
Hemoglobin (Hb) levels have emerged as a useful tool for risk stratification and the prediction of outcome after myocardial infarction. We aimed at evaluating the prognostic impact of this parameter among patients in advanced age, where the larger prevalence of anemia and the higher rate of comorbidities could directly impact on the cardiovascular risk. METHODS:All the patients in the ELDERLY-2 trial, were included in this analysis and stratified according to the values of hemoglobin at admission. The primary endpoint of this study was cardiovascular mortality within one year. The secondary endpoints were all-cause mortality, MI, Bleeding Academic Research Consortium (BARC) type 2-3 or 5 bleeding, any stroke, re-hospitalization for cardiovascular event or stent thrombosis (probable or definite) within 12 months after index admission. RESULTS:We included in our analysis 1364 patients, divided in quartiles of Hb values (<12.2; 12.2-13.39; 13.44-14.49; ≥ 4.5 g/dl). At a mean follow- up of 330.4 ± 99.9 days cardiovascular mortality was increased in patients with lower Hb (HR[95%CI] = 0.76 [0.59-0.97], p = 0.03). Results were no more significant after correction for baseline differences (adjusted HR[95%CI] = 1.22 [0.41-3.6], p = 0.16). Similar results were observed for overall mortality. At subgroup analysis, (according to Hb median values) a significant interaction was observed only with the type of antiplatelet therapy, but not with major high-risk subsets of patients. CONCLUSIONS:Among elderly patients with acute coronary syndrome managed invasively, lower hemoglobin at admission is associated with higher cardiovascular and all-cause mortality and major ischemic events, mainly explained by the higher risk profile.
10.1016/j.ijcard.2022.07.033
Microbleeds and clinical outcome in acute mild stroke patients treated with antiplatelet therapy: ADS post-hoc analysis.
Aoki Junya,Iguchi Yasuyuki,Urabe Takao,Yamagami Hiroshi,Todo Kenichi,Fujimoto Shigeru,Idomari Koji,Kaneko Nobuyuki,Iwanaga Takeshi,Terasaki Tadashi,Tanaka Ryota,Yamamoto Nobuaki,Tsujino Akira,Nomura Koichi,Abe Koji,Uno Masaaki,Okada Yasushi,Matsuoka Hideki,Yamagata Sen,Yamamoto Yasumasa,Yonehara Toshiro,Inoue Takeshi,Yagita Yoshiki,Kimura Kazumi
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
BACKGROUND AND PURPOSE:In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. METHODS:The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. RESULTS:Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). CONCLUSIONS:MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.
10.1016/j.jocn.2021.04.028
Comparison between thromboelastography and the conventional coagulation test in detecting effects of antiplatelet agents after endovascular treatments in acute ischemic stroke patients: A STROBE-compliant study.
Liang Chunyang,Yang Yang,He Zijun,Ma Shang,Qu Xuenan,Luo Yongchun,Shen Chunsen,Xu Ruxiang
Medicine
Antiplatelet agents have been administered to patients with acute ischemic stroke after endovascular therapy. This study was designed to provide initial data to compare thromboelastography (TEG) with the conventional coagulation test (CCT) to analyze the coagulation function of antiplatelet drugs in such patients.The present retrospective cohort study included 240 patients who received endovascular therapy from September 2012 to December 2017. The baseline and clinical characteristics of these patients were collected with respect to TEG (parameters: R, K, maximal amplitude (MA), and α angle) and CCT (parameters: PT, activated partial thromboplastin time (APTT), fibrinogen (FIB), international normalized ratio (INR), and platelet count (PLT)) on day 5 after aspirin and clopidogrel post-endovascular interventions. The correlation and agreement of these 2 detecting methods were analyzed. Additionally, the area under the receiver operating characteristic curve (AUROC) was used to analyze the effectiveness of these 2 methods in detecting unfavorable clinical outcomes, including symptomatic intracranial hemorrhage and early neurological deterioration.The 3 pairs of parameters (R and APTT, K and APTT, and α angle and FIB) were in agreement for identifying hypercoagulability, while R and APTT, K and APTT, K and PLT, and α angle and PLT were in agreement for identifying hypocoagulability. The AUROC of parameter R for detecting symptomatic intracranial hemorrhage was 0.817, while that of parameter FIB for predicting early neurological deterioration was 0.887.Parameter FIB derived from CCT might be advantageous for evaluating early neurological deterioration, while parameter R detected by TEG might be superior for evaluating symptomatic intracranial hemorrhage.
10.1097/MD.0000000000019447
Changes in the Plasma and Platelet Nitric Oxide Biotransformation Metabolites during Ischemic Stroke-A Dynamic Human LC/MS Metabolomic Study.
Antioxidants (Basel, Switzerland)
Despite improvement in the management of modifiable cardiovascular risk factors, ischemic stroke remains the leading cause of morbidity and mortality in the adult population. The aim of this study was to analyze the time-dependent dynamic differences in expression of the nitric oxide (NO) metabolic pathway in the platelet and plasma compartment between subjects with and without ischemic stroke. Additionally, the interplay between these parameters and platelet aggregation was investigated. A total of 418 patients in acute phase of non-cardioembolic stroke were investigated. Following the inclusion and exclusion criteria, finally 40 subjects with stroke and 39 demographically matched healthy participants were enrolled. Neurological physical examination, followed by assessment of the platelet and plasma levels of the nitric oxide synthase (NOS) inhibitors, including asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), as well as NOS substrate-L-Arginine were performed dynamically three times within the first 24-h, then on the 3rd and 7th day after the stroke onset, which was compared with the healthy control. The platelet L-Arginine concentration was significantly higher on the 1st and 3rd day of stroke, while the plasma levels were significantly lower on exact days in comparison to the control. The competitive NOS-inhibitors in platelets were stably elevated in stroke subjects, whereas no significant differences in plasma compartment were noted. The arachidonic-acid-induced platelet aggregation was negatively associated with the platelet NOS substrate bioavailability, as assessed by the L−Arginine ADMA-ratio on the 3rd and 7th day. Subjects with non-cardioembolic ischemic stroke are characterized by elevated platelet levels of NOS inhibitors. Management of stroke results in increasing the platelet L-Arginine concentration and subsequent NO bioavailability in the platelet compartment.
10.3390/antiox11050955
Platelet indices as prognostic markers of ischemic stroke and their correlation with lipid profile.
Clinical neurology and neurosurgery
OBJECTIVE:Stroke is the cause of one in eight deaths and adds a dreadful burden of disability for the patients. Ischemic stroke is caused by a loss of blood supply to brain due to sudden occlusion of the arterial system, caused by an emboli or thrombus. Our aim was to correlate platelet indices, total cholesterol ratio, and various comorbidities with stroke. METHODS:A cross-sectional study was performed from 2020-2022 with 132 stroke patients admitted to the SRM Medical College Hospital and Research Center, India. Detailed clinical examination was performed. Venous blood samples were drawn at the time of admission to estimate platelet count, mean platelet volume (MPV), platelet distribution width (PDW), and platelet crit (PCT). Overnight fasting serum samples were obtained for lipid profiling. RESULTS:Among the participants in our study, maximum belonged to the age group 50 to 59 years (34.1%) and majority were males (79.5%). In terms of comorbidities, 85.6% of the participants had diabetes, 42.4% had hypertension and 22% had dyslipaedemia. All platelet and lipid parameters were found to be similar between patients with and without comorbidities. While all platelet indices increased with the increase in severity of stroke, we found that PDW is most reliable in predicting stroke with an area under the receiver operator curve of 0.942, with a sensitivity and specificity of 92.1% at cut-off value 14. All platelet parameters also significantly increased in patients with severe lipid dysfuction, establishing a correlation between lipid profile, platelet indices and stroke. CONCULSION:We found a significant relationship between all platelet parameters and stroke. Thus, we believe that patients with risk factors for atherosclerosis should have their platelet indices assessed periodically before the development of cerebrovascular events. Furthermore, dyslipidemia if properly treated, is a modifiable risk factor for stroke, which can decrease morbidity and mortality leading to a healthier society.
10.1016/j.clineuro.2024.108119
Association Between Low-Density Lipoprotein Cholesterol and Platelet Distribution Width in Acute Ischemic Stroke.
Yuan Jian,Cai Jian,Zhao Pei,Zhao Nan,Hong Rong-Hua,Ding Jie,Yang Jin,Fan Qing-Lei,Zhu Jian,Zhou Xia-Jun,Li Ze-Zhi,Zhu De-Sheng,Guan Yang-Tai
Frontiers in neurology
Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for ischemic stroke; however, whether LDL-C affects the platelet deformation function in the peripheral blood circulation in patients with acute ischemic stroke (AIS) is unknown. The present study aimed to investigate the relationship between LDL-C and platelet distribution width (PDW) in AIS patients. We conducted a cross-sectional hospitalized-based study of consecutive 438 patients with AIS within 24 h. Blood samples were collected upon admission and prior to drug administration, and LDL-C and PDW (a parameter that reflects the heterogeneity of platelet volume) were assessed. The relationship between LDL-C and PDW were analyzed by linear curve fitting analyses. Crude and adjusted beta coefficients of LDL-C for PDW with 95% confidence intervals were analyzed using multivariate-adjusted linear regression models. The PDW was significantly higher in the high LDL-C group compared with those in the normal LDL-C group (16.28 ± 0.37 fl vs. 16.08 ± 0.37 fl, < 0.001). Adjusted smoothed plots suggested that there are linear relationships between LDL-C and PDW, and the Pearson's correlation coefficient (95%) was 0.387 (0.304-0.464, < 0.001). The beta coefficients (95% CI) between LDL-C and PDW were 0.15 (0.12-0.18, < 0.001) and 0.14 (0.11-0.18, < 0.001), respectively, in AIS patients before and after adjusting for potential confounders. Our study suggested that the elevated LDL-C level was related to increased PDW among AIS patients.
10.3389/fneur.2021.631227
The impact of platelet indices on ischemic stroke: a Mendelian randomization study and mediation analysis.
Frontiers in neurology
Introduction:Platelet indices (PIs) are hematological parameters that indicate the number, morphology, and activation of platelets. Although some clinical trials suggest an association between PIs and the risk of stroke, the lack of robust evidence is attributed to confounding effects and reverse causation. Objective:This study aimed to evaluate the association between PIs and stroke risk through Mendelian randomization (MR) while exploring the mediating effect of blood pressure in this association. Methods:We identified genetic variants associated with PIs, including platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet crit (PCT), in the UK Biobank ( = 350,474). Relevant genome-wide association studies were utilized to gather summary statistics pertaining to the traits of interest. We primarily used the inverse-variance weighted analysis to obtain estimates for individual causal power. Result:We observed a positive correlation between genetically predicted increases in PCT levels with the stroke onset [PCT: OR (95%CI) = 1.113(1.047, 1.183), < 0.001]. However, no significant causal relationship was found between PLT, PDW, and MPV and the risk of stroke [PLT: OR (95%CI) = 1.037(0.979, 1.098), = 0.221; PDW: OR (95%CI) = 0.973(0.923, 1.024), = 0.294; MPV: OR (95%CI) = 0.990(0.945, 1.038), = 0.675]. Multivariable MR analyses and mediation analysis found that the proportion mediated by systolic blood pressure (SBP) is 23.71% [95%CI (10.85-33.31%)] and the proportion mediated by diastolic blood pressure (DBP) is 28.09% [95%CI (12.92-39.63%)]. Conclusion:This large MR study presents evidence for the potential causal relationship between the PCT level and the risk of ischemic stroke, which might be mediated by blood pressure.
10.3389/fneur.2023.1302008
Fasting Normoglycemia after Intravenous Thrombolysis Predicts Favorable Long-Term Outcome in Non-Diabetic Patients with Acute Ischemic Stroke.
Journal of clinical medicine
BACKGROUND:Only a few studies evaluated the role of fasting glucose levels after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). Importantly, formal analysis concerning the prognostic role of fasting glucose levels in these patients with and without diabetes mellitus (DM) was not performed. Therefore, we assessed whether fasting normoglycemia (FNG) next morning after AIS treated with IVT was associated with 90-day functional outcome in diabetic and non-diabetic patients. METHODS:We retrospectively analyzed 362 AIS patients treated with IVT at The University Hospital in Krakow. FNG was defined as glucose below 5.5 mmol/L. A favorable outcome was defined as modified Rankin score (mRS) of 0-2 at day 90 after AIS onset. RESULTS:At 3-month follow-up, FNG was associated with favorable outcome (87.5% vs. 60.8%, < 0.001) and decreased risk of death (3.1% vs. 18.1%, = 0.002). Independent predictors of a favorable outcome for the whole group were: younger age (HR 0.92, 95%CI 0.89-0.95), lower NIHSS score after IVT (HR 0.70, 95%CI 0.65-0.76), lower maximal systolic blood pressure within 24 h after IVT (HR 0.92, 95%CI 0.89-0.95) and FNG (HR 4.12, 95%CI 1.38-12.35). Association between FNG and mortality was found in univariable (HR 1.47, 95%CI 0.04-0.62) but not in multivariable analysis (HR 0.23, 95%CI 0.03-1.81). In subgroup analyses, FNG was an independent predictor of favorable outcome (HR 5.96, 95%CI 1.42-25.1) only in patients without DM. CONCLUSIONS:FNG next morning after IVT is an independent protective factor for a favorable long-term outcome in non-diabetic AIS patients.
10.3390/jcm10143005
Fatty Acid Levels and Their Inflammatory Metabolites Are Associated with the Nondipping Status and Risk of Obstructive Sleep Apnea Syndrome in Stroke Patients.
Biomedicines
BACKGROUND:This paper discusses the role of inflammation in the pathogenesis of nondipping blood pressure and its role in the pathogenesis of obstructive sleep apnea syndrome. The aim of the study was to assess the impact of free fatty acids (FAs) and their inflammatory metabolites on the nondipping phenomenon and the risk of sleep apnea in stroke patients. METHODS:Sixty-four ischemic stroke patients were included in the prospective study. Group I consisted of 33 patients with a preserved physiological dipping effect (DIP), while group II included 31 patients with the nondipping phenomenon (NDIP). All subjects had FA gas chromatography and inflammatory metabolite measurements performed with the use of liquid chromatography, their 24 h blood pressure was recorded, and they were assessed with the Epworth sleepiness scale (ESS). RESULTS:In the nondipping group a higher level of C16:0 palmitic acid was observed, while lower levels were observed in regard to C20:0 arachidic acid, C22:0 behenic acid and C24:1 nervonic acid. A decreased leukotriene B4 level was recorded in the nondipping group. None of the FAs and derivatives correlated with the ESS scale in the group of patients after stroke. Correlations were observed after dividing into the DIP and NDIP groups. In the DIP group, a higher score of ESS was correlated with numerous FAs and derivatives. Inflammation of a lower degree and a higher level of anti-inflammatory mediators from EPA and DHA acids favored the occurrence of the DIP. A high level of C18: 3n6 gamma linoleic acid indicating advanced inflammation, intensified the NDIP effect. CONCLUSIONS:We demonstrated potential novel associations between the FA levels and eicosanoids in the pathogenesis of the nondipping phenomenon. There are common connections between fatty acids, their metabolites, inflammation, obstructive sleep apnea syndrome and nondipping in stroke patients.
10.3390/biomedicines10092200
Neurologically asymptomatic patients frequently present cerebral injuries during malignant hypertension: a MRI study.
Journal of hypertension
BACKGROUND:Acute and diffuse microvascular damage characterizes malignant hypertension (MHT), the deadliest form of hypertension (HTN). Although its ophthalmological, renal and cardiological repercussions are well known, brain involvement is considered rare with few descriptions, although it is one of the main causes of death. We hypothesized that brain MRI abnormalities are common in MHT, even in patients without objective neurological signs. METHOD:We analyzed retrospectively the brain MRI of patients admitted for acute MHT between 2008 and 2018 in Bordeaux University Hospital, regardless of their neurological status. A trained operator analyzed every brain MRI, looking for posterior reversible encephalopathy syndrome (PRES), ischemic stroke, intracerebral hematoma (ICH) and microangiopathy markers. We included 58 patients without neurological signs, 66% were men, and mean age was 45.6 ± 11.3 years. RESULTS:Brain MRI were normal in 26% of patients but we found at least one acute abnormality on brain MRI in 29% and an Small Vessel Disease score (SVD score) of two or higher in 52%. In patients with neurological signs, these findings were 9, 53 and 70%, respectively. A PRES was found in 16% of asymptomatic patients and 31% had an ischemic stroke and/or a cerebral hematoma. CONCLUSION:PRES, recent hematoma, ischemic stroke and severe cerebral microangiopathy are common findings in MHT patients without neurological signs on admission. The impact of these findings on patient management, and their cerebrovascular and cognitive prognostic value, should be established. Brain MRI might need to become systematic in patients suffering from MHT episodes.
10.1097/HJH.0000000000002950
Hypoperfusion Intensity Ratio Predicts Malignant Edema and Functional Outcome in Large-Vessel Occlusive Stroke with Poor Revascularization.
Murray Nick M,Culbertson Collin J,Wolman Dylan N,Mlynash Michael,Lansberg Maarten G
Neurocritical care
BACKGROUND AND OBJECTIVE:Malignant cerebral edema (MCE) is a well-known complication in patients with acute ischemic stroke with core infarcts ≥ 80 mL caused by large-vessel occlusions. MCE can also develop in patients with smaller infarcts with moderate -to-large volume of tissue at risk who do not achieve successful revascularization with endovascular thrombectomy (ET). Features that predict the development of MCE in this population are not well-described. We aim to identify predictors of MCE and 90-day functional outcome in stroke patients with an anterior circulation large vessel occlusion (LVO) and a < 80 mL ischemic core who do not achieve complete reperfusion. METHODS:We reviewed our institutional stroke registry and included patients who achieved unsuccessful revascularization, mTICI 0-2a, after ET and whose baseline imaging was notable for a core infarct < 80 mL, a T > 6 s volume ≥ 80 mL, and a mismatch ratio ≥ 1.8. MCE was defined as ≥ 5 mm of midline shift on follow-up imaging, obtained 6-48 h after the pre-ET perfusion scan. RESULTS:Thirty-six patients met inclusion criteria. Unadjusted analysis demonstrated that younger age, higher systolic blood pressure, larger core volume, and higher hypoperfusion intensity ratio (HIR) were associated with MCE (all p < 0.02). In multivariate logistic regression analysis, age, HIR, and core infarct volume were independent predictors of MCE. The optimal HIR threshold to predict MCE was ≥ 0.54 (OR 14.7, 95% CI 2.4-78.0, p = 0.003). HIR was also associated with 3-month mRS (HIR ≥ 0.54 for mRS of 3-6: OR 10.8, 95% CI 1.9-44.0, p = 0.02). CONCLUSIONS:Younger age, larger core infarct volume, and higher HIR are predictive of MCE in patients with anterior circulation LVO, moderate-to-large tissue at risk, and suboptimal revascularization. HIR is correlated with three-month functional outcomes.
10.1007/s12028-020-01152-6
Lower middle cerebral artery blood velocity during low-volume high-intensity interval exercise in chronic stroke.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
High-intensity interval training (HIIE) may present unique challenges to the cerebrovascular system in individuals post-stroke. We hypothesized lower middle cerebral artery blood velocity (MCAv) in individuals post-stroke: 1) during 10 minutes of HIIE, 2) immediately following HIIE, and 3) 30 minutes after HIIE, compared to age- and sex-matched controls (CON). We used a recumbent stepper submaximal exercise test to determine workloads for high-intensity and active recovery. Our low volume HIIE protocol consisted of 1-minute intervals for 10 minutes. During HIIE, we measured MCAv, mean arterial pressure (MAP), heart rate (HR), and end tidal carbon dioxide (PCO). We assessed carotid-femoral pulse wave velocity as a measure of arterial stiffness. Fifty participants completed the study (25 post-stroke, 76% ischemic, 32% moderate disability). Individuals post-stroke had lower MCAv during HIIE compared to CON (p = 0.03), which remained 30 minutes after HIIE. Individuals post-stroke had greater arterial stiffness (p = 0.01) which was moderately associated with a smaller MCAv responsiveness during HIIE (r = -0.44). No differences were found for MAP, HR, and PCO. This study suggests individuals post-stroke had a lower MCAv during HIIE compared to their peers, which remained during recovery up to 30 minutes. Arterial stiffness may contribute to the lower cerebrovascular responsiveness post-stroke.
10.1177/0271678X231201472
Risk factors for relapse and nomogram for relapse probability prediction in patients with minor ischemic stroke.
Yu Xian-Feng,Yin Wen-Wen,Huang Chao-Juan,Yuan Xin,Xia Yu,Zhang Wei,Zhou Xia,Sun Zhong-Wu
World journal of clinical cases
BACKGROUND:The identification of risk factors for recurrence in patients with minor ischemic stroke (MIS) is a critical medical need. AIM:To develop a nomogram for individualized prediction of in-hospital recurrence in MIS patients. METHODS:Based on retrospective collection, a single-center study was conducted at the First Affiliated Hospital of Anhui Medical University from January 2014 to December 2019. Univariate and multivariate logistic regression analyses were used to determine the risk factors associated with MIS recurrence. The least absolute shrinkage and selection operator regression was performed for preliminary identification of potential risk factors. Uric acid, systolic blood pressure, serum total bilirubin (STBL), and ferritin were integrated for nomogram construction. The predictive accuracy and calibration of the nomogram model were assessed by the area under the receiver operating characteristic curve (AUC-ROC) and Hosmer-Lemeshow test, respectively. RESULTS:A total of 2216 MIS patients were screened. Among them, 155 were excluded for intravascular therapy, 146 for unknown National Institutes of Health Stroke Scale score, 195 for intracranial hemorrhage, and 247 for progressive stroke. Finally, 1244 patients were subjected to further analysis and divided into a training set ( = 796) and a validation set ( = 448). Multivariate logistic regression analysis revealed that uric acid [odds ratio (OR): 0.997, 95% confidence interval (CI): 0.993-0.999], ferritin (OR: 1.004, 95%CI: 1.002-1.006), and STBL (OR: 0.973, 95%CI: 0.956-0.990) were independently associated with in-hospital recurrence in MIS patients. Our model showed good discrimination; the AUC-ROC value was 0.725 (95%CI: 0.646-0.804) in the training set and 0.717 (95%CI: 0.580-0.785) in the validation set. Moreover, the calibration between nomogram prediction and the actual observation showed good consistency. Hosmer-Lemeshow test results confirmed that the nomogram was well-calibrated ( = 0.850). CONCLUSION:Our present findings suggest that the nomogram may provide individualized prediction of recurrence in MIS patients.
10.12998/wjcc.v9.i31.9440
Risk Profile of Ischemic Stroke Caused by Small-Artery Occlusion vs. Deep Intracerebral Hemorrhage.
Chen Zimo,Mo Jinglin,Xu Jie,Qin Haiqiang,Zheng Huaguang,Pan Yuesong,Meng Xia,Jing Jing,Xiang Xianglong,Wang Yongjun
Frontiers in neurology
Small-artery occlusion (SAO) subtype accounts for a quarter of the cases of ischemic stroke and is mainly caused by pathological changes in cerebral small vessels, which also involve in deep intracerebral hemorrhage (dICH). However, the factors that drive some cases to SAO and others to dICH remained incompletely defined. This study is a cross-sectional study from the China National Stroke Registry that included consecutive patients with ischemic stroke or intracerebral hemorrhage between August 2007 and September 2008. We compared the risk profile between the two subgroups using multivariable logistic regression. A total of 1,135 patients with SAO stroke and 1,125 dICH patients were included for analyses. Generally, patients with SAO stroke were more likely to be male (odds ratio = 0.74, confidence interval = 0.58-0.94) and have diabetes (0.30, 0.22-0.40), higher atherogenic lipid profiles, higher body mass index (0.96, 0.94-0.99), higher waist/height ratio (0.12, 0.03-0.48), higher platelet count (0.84, 0.77-0.91), and higher proportion of abnormal estimated glomerular filtration rate (<90, ml/min/1.73 m) (0.77, 0.62-0.95). Conversely, patients with dICH were more likely to have higher blood pressure parameters, inflammation levels (white blood cell count: 1.61, 1.48-1.76; high sensitivity C-reactive protein: 2.07, 1.36-3.16), and high-density lipoprotein-c (1.57, 1.25-1.98). The risk profile between SAO stroke and dICH were different. Furthermore, despite of traditional indexes, waist/height ratio, platelet count, inflammation levels, lipid profile, and estimated glomerular filtration rate also play important roles in driving arteriolosclerosis into opposite ends.
10.3389/fneur.2019.01213
Non-alcoholic fatty liver disease frequency and associated factors at admission of acute stroke.
Hepatology international
BACKGROUND/PURPOSE OF THE STUDY:If non-alcoholic fatty liver disease (NAFLD) frequency is very high in stroke patients, NAFLD may be a risk factor for stroke and identifying factors of NAFLD presence may lead to stroke prevention. This retrospective study aimed to investigate whether NAFLD frequency was very high and identify factors associated with NAFLD presence at acute stroke admission. METHODS:We included stroke patients aged 40 - 79 years who (1) were admitted from 2016 to 2019, within 24 h of onset; (2) underwent abdominal ultrasonography; and (3) underwent blood examination of biomarkers. We evaluated the frequency and significant factors of NAFLD presence. RESULTS:Among 1672 stroke patients, 676 patients met our inclusion criteria, and 267 patients (39.5%) had NAFLD. Compared to patients without NAFLD, patients with NAFLD were young; had high anthropometric values; high blood pressure; low aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT) ratio; high levels of liver enzymes, serum albumin, HbA1c, and serum lipids; low-density lipoprotein; high serum level of some fatty acids; and high fatty acid% of palmitic acid (PA) and dihomo-gamma-linolenic acid (DGLA). After excluding variables with multicollinearity, independent NAFLD-presence factors were high body mass index (BMI), low AST/ALT ratio, high serum albumin level, high PA%, and high DGLA level. CONCLUSIONS:The frequency of NAFLD was high in our patient group. Significant NAFLD-presence factors were high BMI, low AST/ALT ratio, high serum albumin level, high PA%, and high DGLA level. A further study is warranted to determine the effects of the NAFLD-presence factors on stroke onset or prevention.
10.1007/s12072-021-10253-z
Left ventricular myocardial dysfunction in young and middle-aged ischemic stroke patients: the Norwegian stroke in the young study.
Saeed Sahrai,Gerdts Eva,Waje-Andreassen Ulrike,Fromm Annette,Pristaj Nadia,Naess Halvor,Matre Knut
Journal of hypertension
BACKGROUND:Hypertension is highly prevalent in ischemic stroke patients, but less is known about its impact on subclinical left ventricular (LV) dysfunction in such patients. METHODS:Conventional and speckle tracking echocardiography was performed in 276 young (15-44 years) and middle-aged (45-60 years) ischemic stroke patients (mean age 50 ± 9 years, 66% men). Hypertension was defined as a history of hypertension, use of antihypertensive medications, persistently elevated blood pressure (BP) during hospitalization or elevated clinic BP (≥140/90 mmHg) and ambulatory BP (≥130/80 mmHg) at follow-up visits. LV myocardial dysfunction was assessed by peak systolic global longitudinal (GLS) and circumferential strain (GCS). RESULTS:Hypertension was present in 68% of patients and associated with higher age, BMI and LV mass, male sex and the presence of diabetes (all P < 0.01). Compared with normotensive patients, hypertensive patients had significantly lower peak systolic GLS (-16 ± 3 vs. -19 ± 2%, P < 0.001) and GCS (-16 ± 3 vs. -18 ± 4%, P < 0.001) while ejection fraction did not differ between groups (P = 0.134). In univariable regression analyses, reduced peak systolic GLS and GCS were both associated with hypertension (β = 0.43 and 0.29, respectively, both P < 0.001). The association with hypertension remained significant for GLS (β = 0.25) after adjustment for LV mass, ejection fraction, male sex, obesity and diabetes (multiple R = 0.35, P < 0.001), whereas the association of hypertension with reduced peak systolic GCS was attenuated. CONCLUSION:In ischemic stroke survivors, hypertension was associated with reduced peak systolic GLS but not GCS independent of confounders.
10.1097/HJH.0000000000001925
Association between increased N-terminal pro-brain natriuretic peptide level and poor clinical outcomes after acute ischemic stroke.
Yang Jingyuan,Zhong Chongke,Wang Aili,Xu Tan,Bu Xiaoqing,Peng Yanbo,Wang Jinchao,Peng Hao,Li Qunwei,Ju Zhong,Geng Deqin,Zhang Yonghong,He Jiang,
Journal of the neurological sciences
BACKGROUND AND PURPOSE:N-terminal pro-brain natriuretic peptide (NT-proBNP) has been shown to be associated with the prognosis of cardiovascular diseases and NT-proBNP level is elevated in patients with acute ischemic stroke. However, the association between NT-proBNP and poor prognosis after ischemic stroke is still uncertain. The aim of this study was to examine whether serum NT-proBNP is associated with global clinical outcomes in a large cohort of patients with acute ischemic stroke. METHODS:Baseline serum NT-proBNP level was measured in a subset of 3126 patients with acute ischemic stroke, and the patients were followed up to assess their clinical outcomes within 1year after the stroke. Cox proportional hazard models and logistic regression models were used to assess the effects of NT-proBNP on the primary outcome (composite outcome of death and vascular events) and poor functional outcomes. RESULTS:During 1year of follow-up, 278 (9.0%) patients with a primary outcome and 685 (22.1%) patients with a poor functional outcome were identified. The cumulative incidence of primary outcomes increased across serum NT-proBNP quartiles (log-rank P<0.001). Hazard ratios (95% confidence interval) of the highest quartile compared with the lowest quartile were 1.47 (1.01-2.13) for the primary outcome, 1.79 (1.07-2.98) for death after multivariable adjustment. In addition, serum NT-proBNP was also associated with poor functional outcomes (odds ratio, 1.47; 95% confidence interval, 1.11-1.94; P=0.008). CONCLUSIONS:This study showed that high NT-proBNP levels increased the risk of a composite outcome of death and vascular events and poor functional outcomes at 1year after stroke onset among ischemic stroke patients with elevated blood pressure, suggesting that NT-proBNP might be a potential prognostic factor for ischemic stroke.
10.1016/j.jns.2017.10.014
A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.
Weng Ze-An,Huang Xiao-Xiong,Deng Die,Yang Zhen-Guo,Li Shu-Yuan,Zang Jian-Kun,Li Yu-Feng,Liu Yan-Fang,Wu You-Sheng,Zhang Tian-Yuan,Su Xuan-Lin,Lu Dan,Xu An-Ding
Frontiers in neurology
Background:We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods:A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, = 387) and the testing set (30%, = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results:After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets ( < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful. Conclusions:The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.
10.3389/fneur.2022.774654
Correlation and predictive value of platelet biological indicators and recurrence of large-artery atherosclerosis type of ischemic stroke.
Biotechnology & genetic engineering reviews
Large-artery atherosclerosis type of ischemic stroke happens when a blood clot forms in a major artery that carries blood to the brain. This causes a blockage and a decrease in blood flow to the brain tissue making up approximately 15-20% of all cases. This type of stroke is more prevalent in older adults and those with risk factors such as high blood pressure, high cholesterol, diabetes, smoking, and a family history of stroke. To investigate the correlation and predictive value of platelet-related biological indicators with recurrence of large-artery atherosclerosis type of ischemic stroke (LAA-IS)2. The patients were divided into a relapse group (R, = 40) and non-relapse group (NR, = 45). Platelet-related biological indicators were collected from both groups to analyze their correlation with neurological impairment score (NIHSS score). Risk factors were analyzed using binary logistic regression and a survival curve (ROC) was drawn to evaluate the predictive effect of clinical platelet-related biological indicators on LAA-IS recurrence. This study confirmed that PAg-ADP, PAg-COL, and FIB are closely related to the formation of LAA-IS due to carotid atherosclerosis, and the combined PAg-ADP, PAg-COL, and FIB index levels are the most promising for assessing the prognostic development of recurrence in patients with LAA-IS. Combined monitoring of platelet aggregation rate and FIB index is of important evaluation value in judging the recurrence prognosis of LAA-IS patients.
10.1080/02648725.2023.2196879
Pulse pressure level after acute ischemic stroke is associated with early neurological deterioration.
Experimental and therapeutic medicine
Early neurological deterioration (END) is an unfavorable outcome of acute ischemic stroke and is associated with poor prognosis. Blood pressure variability has been suggested to be involved in the development of END. Therefore, the present study investigated the association between blood pressure variability and the development of END. In the present prospective observational study, 286 patients who developed acute ischemic stroke and then hospitalized within 24 h of stroke onset were recruited. Blood pressure parameters (systolic blood pressure, diastolic blood pressure and pulse pressure) were monitored using a 24 h ambulatory sphygmomanometer within 72 h of ischemic onset. Clinical characteristics were also recorded. Multivariate logistic regression analysis was used to analyze the possible relationship between blood pressure parameters and END after adjustment for confounders. Of the 286 patients in the present study, 64 (22.3%) developed END. Pulse pressure variables, including the mean of 24-h pulse pressure (24-h PP) and the mean of daytime pulse pressure (Day PP), were found to be higher in the END group compared with those in the non-END group (P<0.05). Multivariate logistic regression analysis revealed that the blood pressure parameters 24-h PP [odds ratio (OR), 1.08; 95% CI, 1.01-1.16; P=0.02) and Day PP (OR, 1.20; 95% CI, 1.011-1.45; P=0.04) were significantly associated with END. These findings suggest that the pulse pressure level fluctuations during the acute stage of ischemic stroke can serve important roles in the development of END, which worsens outcomes after stroke.
10.3892/etm.2023.12349
Risk Factors of Neurological Deterioration in Patients with Cerebral Infarction due to Large-Artery Atherosclerosis.
Yamamoto Nobuaki,Satomi Junichiro,Yamamoto Yuki,Shono Kenji,Kanematsu Yasuhisa,Izumi Yuishin,Nagahiro Shinji,Kaji Ryuji
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:In some patients with acute ischemic stroke, neurological deterioration (ND) is observed, and it is difficult to predict at the time of admission. Especially in some patients with large-artery atherosclerosis (LAA), aggressive medical treatments and surgical interventions might be helpful to prevent ND. Therefore, we investigated factors associated with ND in patients with LAA. METHODS:We studied patients with LAA who were admitted to our hospital. We divided them into 2 groups with (group 1) and without deterioration (group 2), and evaluated their medical records, risk factors, and radiological findings, such as number of diffusion-positive lesion and degree of stenosis. RESULTS:Our study population consisted of 171 patients; 71 (41.5%) did and 100 (58.5%) did not suffer deterioration. By univariate analysis, blood pressure (BP), heart rate, National Institutes of Health Stroke Scale (NIHSS) score, number of diffusion-positive lesion, count of red blood cell, high-density lipoprotein, and degree of stenosis differed significantly between the 2 groups. By multivariate analysis, systolic BP (≥170 mm Hg, odds ratio: 7.20, P <.001) was associated with ND. Furthermore, number of diffusion-weighted image (DWI)-positive lesion (≥8), degree of stenosis (>80.0%), and NIHSS score (≥4) were also independent factors associated with ND. CONCLUSIONS:High BP, severity of neurological deficit at the time of admission, and radiological findings, such as degree of stenosis and number of DWI-positive lesion, are independently associated with ND in patients with LAA.
10.1016/j.jstrokecerebrovasdis.2017.04.011
Usefulness of cardiometabolic index for the estimation of ischemic stroke risk among general population in rural China.
Wang Haoyu,Chen Yintao,Guo Xiaofan,Chang Ye,Sun Yingxian
Postgraduate medicine
OBJECTIVES:Cardiometabolic index (CMI) has been recognized as a novel and practical marker for the assessment of cardiometabolic risk as it is independently related to diabetes and atherosclerotic progression. This study tested the hypothesis that CMI represents a risk of ischemic stroke in a general population of rural China. METHODS:From July 2012 to August 2013, we examined data from a large cross-sectional study of 11,345 participants (mean age 53.8 years; 60.8% females) who underwent biochemical determinations and anthropometric measurements in rural areas of northeast China. Ischemic stroke was documented as a history of cerebrovascular events and verified by medical record review. RESULTS:The prevalence of ischemic stroke was given to 3.1% of females and 3.2% of males. The cardio-metabolic profile was notably more adverse in ischemic stroke groups, irrespective of gender. A dose-response manner was detected for the prevalence of ischemic stroke, exhibiting a significant increase from the lowest to the highest quartiles of CMI (1.2% to 6.4% in females, P for trend<0.001; 2.3% to 4.3% in males, P for trend = 0.017). In multivariable analysis, for every 1 SD increment in CMI, the probability of ischemic stroke increased by 18% in females and 14% in males, respectively. The odds ratios for ischemic stroke comparing the top versus bottom quartiles of CMI were 2.047 (95%CI: 1.168-3.587) for females and 1.722 (95%CI: 1.019-2.910) for males. According to the area under receiver operating characteristic (AUC), the discrimination power of CMI in predicting ischemic stroke was relatively higher for females (AUC: 0.685) than males (AUC: 0.573). CONCLUSION:The strong and independent association of CMI with ischemic stroke in females, in comparison with the much lesser degree in males, provides further insight to better stratify by sex in investigations of ischemic stroke and solidly corroborates the potential role of ischemic stroke prevention targeted at CMI.
10.1080/00325481.2017.1375714
Carotid Intima-Media Thickness and the Risk of First Stroke in Patients With Hypertension.
Sun Pengfei,Liu Lishun,Liu Chengzhang,Zhang Yan,Yang Ying,Qin Xianhui,Li Jianping,Cao Jingjing,Zhang Yuanyuan,Zhou Ziyi,Xu Xiping,Huo Yong
Stroke
Background and Purpose- This study aimed to investigate the association between mean carotid intima-media thickness (cIMT) and the risk of first stroke and examine any possible effect modifiers in patients with hypertension. Methods- A total of 11 547 hypertensive participants without history of stroke from the CSPPT (China Stroke Primary Prevention Trial) were included in this analysis. The primary outcome was first stroke. Results- Over a median follow-up of 4.4 years, 726 first strokes were identified, of which 631 were ischemic, and 90 were hemorrhagic. A per SD increase in mean cIMT was positively associated with the risk of first stroke (hazard ratio [HR], 1.11 [95% CI, 1.03-1.20]), and first ischemic stroke (HR, 1.10 [95% CI, 1.01-1.20]). Moreover, when cIMT was categorized in quartiles, the higher risks of first stroke (HR, 1.31 [95% CI, 1.06-1.61]) and first hemorrhagic stroke (HR, 2.25 [95% CI, 1.11-4.58]) were found in participants in quartile 2 to 4 (≥0.66 mm), compared with those in quartile 1 (<0.66 mm). More importantly, the cIMT-first stroke association was significantly stronger in participants with higher mean arterial pressure (≥109.3 [quintile 5] versus <109.3 mm Hg, -interaction=0.024) or diastolic blood pressure levels (≥90.7 [quintile 5] versus <90.7 mm Hg, -interaction=0.009). Conclusions- There was a significant positive association between baseline cIMT and the risk of first stroke in patients with hypertension. This association was even stronger among those with higher mean arterial pressure or diastolic blood pressure levels.
10.1161/STROKEAHA.119.026587
[Association between platelet parameters and risk for stroke in people with different blood pressure levels: Dongfeng-Tongji cohort].
Geng Z Y,Xu X D,Wang Q H,Jiang Q,Lin Y H,Jia C Y,Wu T C,He M A
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
To explore the associations of platelet parameters platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) with the risk for stroke in people with different blood pressure levels. All the participants were from Dongfeng-Tongji cohort, including 38 295 retired employees from Dongfeng Motor Corporation at the first follow-up survey. After excluding participants with coronary heart disease, stroke, cancer, history of platelet influential drug use and those with missed data of platelet parameters or blood pressure or lost to follow-up, finally a total of 21 294 participants were included in this study. All the participants completed baseline questionnaires, physical examinations, clinical biochemical tests, and blood sample collection. Cox proportional hazard models were used to estimate the hazard ratios (s) and the corresponding 95% confident intervals (s) for the associations between platelet parameters and risk for stroke in people with different blood pressure levels. After a mean follow-up of 8.0 years, 1 578 participants developed incident stroke [1 266 ischemic stroke (IS) cases and 312 hemorrhagic stroke (HS) cases]. Compared with the participants with PLT<188×10/L, those with PLT≥188×10/L among hypertension cases were significantly associated with higher risks for stroke and IS (stroke: =1.27, 95%: 1.12-1.44; IS: =1.39, 95%: 1.21-1.60). Among hypertension group, compared with participants with PCT<0.165%, PCT≥0.165% were significantly associated with higher risk for stroke (=1.15, 95%: 1.01-1.30) and lower risk for HS (=0.70, 95%: 0.53-0.93); Among non-hypertension and hypertension group, PCT ≥0.165% were significantly associated with higher risks of IS (=1.27, 95%: 1.05-1.54; =1.31, 95%: 1.14-1.50). MPV and PDW were not significantly associated with risk for stroke. Risk for stroke increased significantly in hypertension cases with different platelet parameters levels compared with non-hypertension cases with lower levels of each platelet parameters. Higher levels of PLT and PCT could increase the risks for stroke and IS in middle-aged and elderly hypertension patients, and lower levels of PCT could decrease the risk for HS in hypertension patients.
10.3760/cma.j.cn112338-20210320-00235
Assessment of the Role of Carotid Atherosclerosis in the Association Between Major Cardiovascular Risk Factors and Ischemic Stroke Subtypes.
Parish Sarah,Arnold Matthew,Clarke Robert,Du Huaidong,Wan Eric,Kurmi Om,Chen Yiping,Guo Yu,Bian Zheng,Collins Rory,Li Liming,Chen Zhengming,
JAMA network open
Importance:A better understanding of the role of atherosclerosis in the development of ischemic stroke subtypes could help to improve strategies for prevention of stroke worldwide. Objective:To assess the role of carotid atherosclerosis in the association between major cardiovascular risk factors and ischemic stroke subtypes. Design, Setting, and Participants:The prospective China Kadoorie Biobank cohort study was conducted in the general population of 5 urban and 5 rural areas in China, with a baseline survey obtained between June 2004 and July 2008. A random sample of 23 973 participants with no history of cardiovascular disease at enrollment who had carotid artery ultrasonographic measurements recorded at a resurvey from September 2013 to June 2014 were included. Data analysis was performed from July 1, 2016, to April 10, 2019. Exposures:Major cardiovascular risk factors (ie, blood pressure [BP], blood lipid levels, smoking, and diabetes). Main Outcomes and Measures:Carotid ultrasonographic measures of plaque burden (derived from number and maximum size of carotid artery plaques at resurvey) and first ischemic stroke during follow-up (n = 952), with subtyping (data release, August 2018) as lacunar (n = 263), probable large artery (n = 193), probable cardioembolic (n = 66), or unconfirmed (n = 430). Associations between cardiovascular risk factors, carotid plaque burden, and ischemic stroke subtypes were adjusted for age, sex, and geographic area. Results:The 23 973 participants in the study had a mean (SD) age of 50.6 (10.0) years, and 14 833 (61.9%) were women. Systolic BP had a stronger association (odds ratio [OR] per SD, 1.51; 95% CI, 1.42-1.61) than plaque burden (OR per SD, 1.34; 95% CI, 1.26-1.44) with ischemic stroke, and the associations of systolic BP with each subtype of ischemic stroke were modestly attenuated by adjustment for plaque burden. After adjustment for BP, plaque burden had a stronger association with probable large artery stroke (OR, 1.43; 95% CI, 1.24-1.63) than with lacunar stroke (OR, 1.25; 95% CI, 1.10-1.43) but was not associated with probable cardioembolic stroke (OR, 1.06; 95% CI, 0.83-1.36). Conclusions and Relevance:Although BP was an important risk factor for all ischemic stroke subtypes, carotid atherosclerosis was an important risk factor only for large artery and lacunar strokes, suggesting that drug treatments targeting atherosclerosis may reduce the risk of stroke subtypes to different extents.
10.1001/jamanetworkopen.2019.4873
Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.
Journal of hypertension
BACKGROUND:We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. METHODS:We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. RESULTS:At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P < 0.001 among subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups among subgroups. However, there was a significant interaction between antihypertensive treatment and baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. CONCLUSION:Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01840072.
10.1097/HJH.0000000000001690
Time Window for Induced Hypertension in Acute Small Vessel Occlusive Stroke With Early Neurological Deterioration.
Stroke
BACKGROUND:Therapeutic-induced hypertension treatment (iHTN) is helpful for alleviating early neurological deterioration (END) in acute small vessel occlusive stroke. We examined the time parameters related to iHTN effectiveness in these patients. METHODS:We retrospectively reviewed patients with acute small vessel occlusive stroke who underwent iHTN for END, defined as an increase of ≥2 points in total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 point in motor items of NIHSS. The primary outcome was an early neurological improvement (ENI; a decrease of ≥2 points in total NIHSS score or ≥1 point in motor items of NIHSS), and the secondary outcome was any neurological improvement (a decrease of ≥1 point in the total NIHSS score). We conducted a multivariable logistic regression analysis, adjusting for demographics, risk factors, baseline clinical status, and intervention-related variables. We also generated a restricted cubic spline curve for the END-to-iHTN time cutoff. RESULTS:Among the 1062 patients with small vessel occlusive stroke screened between 2017 and 2021, 136 patients who received iHTN within 24 hours from END were included. The mean age was 65.1 (±12.0) years, and 61.0% were male. Sixty-five (47.8%) patients showed ENI and 77 (56.6%) patients showed any neurological improvement. END-to-iHTN time was significantly shorter in patients with ENI (150 [49-322] versus 290 [97-545] minutes; =0.018) or any neurological improvement (150 [50-315] versus 300 [130-573] minutes; =0.002). A 10-minute increase in the time between END and iHTN decreased the odds of achieving ENI (odds ratio, 0.984 [95% CI, 0.970-0.997]; =0.019) or any neurological improvement (odds ratio, 0.978 [95% CI, 0.964-0.992]; =0.002). The restricted cubic spline curve showed that the odds ratio of ENI reached its minimum at ≈3 hours. CONCLUSIONS:Among patients with small vessel occlusive stroke with END, a shorter interval between END and the initiation of iHTN was associated with increased odds of achieving neurological improvement. The efficacy of iHTN may be limited to induction within the first 3 hours of END.
10.1161/STROKEAHA.123.044334
Age and sex-specific associations of carotid pulsatility with small vessel disease burden in transient ischemic attack and ischemic stroke.
International journal of stroke : official journal of the International Stroke Society
Background Although large artery stiffness has been implicated in the pathogenesis of cerebral small vessel disease, whether carotid pulsatility, a convenient surrogate marker of arterial stiffness, is similarly associated with global burden of small vessel disease is unknown. Aims To determine the age and sex-specific associations of carotid pulsatility with global burden of small vessel disease. Methods We studied consecutive patients with transient ischemic attack or non-disabling ischemic stroke from the Oxford Vascular Study who had a brain MRI and carotid duplex ultrasound during 2002-2014. We determined clinical correlates of common carotid artery (CCA) and internal carotid artery (ICA) pulsatility index (PI) and their associations with the total small vessel disease score on MRI, stratified by age (median = 72). Results In 587 patients, correlates of CCA and ICA-PI were both independently associated with age, diabetes, and premorbid mean pulse pressure after adjustment for age, sex, and cardiovascular risk factors (all p < 0.05). ICA-PI was strongly associated with small vessel disease markers and burden, particularly lacunes, in patients aged<70 (age and sex-adjusted odds ratio of top vs. bottom pulsatility index quartile: 5.35, 1.95-14.70, p = 0.001; increasing small vessel disease score: 2.30, 1.01-5.25, p = 0.048), but not in patients aged ≥ 70 ( p > 0.05). No associations between CCA-PI with small vessel disease score were noted at any age. In 94 consecutive patients who also received transcranial Doppler ultrasound, strong associations between middle cerebral artery (MCA)-PI and an increasing small vessel disease score were noted (unadjusted OR-MCA: 4.26, 1.45-12.55, p = 0.009; ICA: 2.37, 0.81-6.87, p = 0.11; CCA: 1.33, 0.45-3.96, p=0.61). Conclusions ICA and MCA-PI are associated with global small vessel disease burden, especially in individuals aged<70 and may be causally related.
10.1177/1747493018784448
Twenty-four-hour ambulatory blood pressure variability is associated with total magnetic resonance imaging burden of cerebral small-vessel disease.
Yang Shuna,Yuan Junliang,Qin Wei,Yang Lei,Fan Huimin,Li Yue,Hu Wenli
Clinical interventions in aging
BACKGROUND:Lacunae, brain atrophy, white matter hyperintensity, enlarged perivascular space and microbleed are magnetic resonance imaging (MRI) markers of cerebral small-vessel disease (cSVD). Studies have reported that higher blood pressure variability (BPV) predicted cardiovascular risk in hypertensive patients; however, the association between BPV and the total MRI burden of cSVD has not been investigated. In this study, we aimed to explore this relationship between BPV and cSVD MRI burden. METHODS:We prospectively recruited patients who attended our hospital for annual physical examination. Twenty-four-hour ambulatory BP monitoring was performed using an automated system. BPV was quantified by SD, weighted SD, and coefficient of variation. One point was awarded for the presence of each marker, producing a score between 0 and 5. Spearman correlation and ordinal logistic regression analyses were used to test the relationship between BPV and total cSVD MRI burden. RESULTS:A total of 251 subjects with an average age of 68 years were enrolled in this study, and 52.6% were male; 163 (64.94%) had one or more markers of cSVD. Correlation analysis indicated that higher systolic BP (SBP) levels and BPV metrics of SBP were positively related to higher cSVD burden. Ordinal logistic regression analyses demonstrated that higher SBP levels and SBP variability were independent risk factors for cSVD. There were no significant differences in 24-hour, day and night diastolic BP levels or BPV metrics of diastolic BP among the five subgroups. CONCLUSION:Twenty-four-hour, day and night SBP levels and SBP variability were positively related to cSVD burden. Higher SBP levels and SBP variability were independent risk factors for cSVD.
10.2147/CIA.S171261
Blood pressure reduction in hypertensive acute ischemic stroke patients does not affect cerebral blood flow.
Kate Mahesh,Asdaghi Negar,Gioia Laura C,Buck Brian,Majumdar Sumit R,Jeerakathil Thomas,Shuaib Ashfaq,Emery Derek,Beaulieu Christian,Butcher Kenneth
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
The effect of blood pressure (BP) reduction on cerebral blood flow (CBF) in acute ischemic stroke is unknown. We measured regional CBF with perfusion-weighted MRI before and after BP treatment in a three-armed non-randomized prospective controlled trial. Treatment arm assignment was based on acute mean arterial pressure (MAP). Patients with (MAP) >120 mmHg ( = 14) were treated with intravenous labetalol and sublingual (SL) nitroglycerin (labetalol group). Those with MAP 100-120 mmHg ( = 17) were treated with SL nitroglycerin (0.3 mg) ('NTG Group') and those with baseline MAP<100 mmHg ( = 18) were not treated with antihypertensive drugs (untreated group). Forty-nine patients (18 female, mean age 65.3 ± 12.9 years) were serially imaged. Labetalol reduced MAP by 12.5 (5.7-17.7) mmHg, = 0.0002. MAP remained stable in the NTG (6.0 (0.4-16, = 0.3) mmHg and untreated groups (-0.3 (-2.3-7.0, = 0.2) mmHg. The volume of total hypoperfused tissue (CBF<18 ml/100 g/min) did not increase after labetalol (-1.1 ((-6.5)-(-0.2)) ml, = 0.1), NTG (0 ((-1.5)-4.5) ml, = 0.72), or no treatment 0.25 ((-10.1)-4.5) ml, = 0.87). Antihypertensive therapy, based on presenting BP, in acute stroke patients was not associated with an increased volume of total hypoperfused tissue.
10.1177/0271678X18774708