Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus.
O'Neill Sean G,Giles Ian,Lambrianides Anastasia,Manson Jessica,D'Cruz David,Schrieber Leslie,March Lyn M,Latchman David S,Isenberg David A,Rahman Anisur
Arthritis and rheumatism
OBJECTIVE:Inflammatory disease activity in patients with systemic lupus erythematosus (SLE) may affect the development of atherosclerosis, contributing to their increased risk of cardiovascular disease (CVD). This process may be mediated by anti-apolipoprotein A-I (anti-Apo A-I), anti-high-density lipoprotein (anti-HDL), and anti-C-reactive protein (anti-CRP) autoantibodies. We undertook this study to examine whether levels of these antibodies rise in association with increased SLE disease activity. METHODS:IgG anti-Apo A-I, anti-HDL, and anti-CRP levels were measured in serum from the following groups: 39 patients with persistently high disease activity (British Isles Lupus Assessment Group [BILAG] A or B score) over the previous 2 years, 42 patients with persistently low disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy controls, 25 individual patients from whom paired samples (at time of disease flare and quiescence) were obtained and compared, 16 patients with newly diagnosed lupus nephritis from whom multiple samples were obtained and who were followed up prospectively for up to 2 years, and 24 patients with SLE who had experienced CVD events. RESULTS:Serum levels of IgG anti-Apo A-I, anti-HDL, and anti-CRP were higher in patients with SLE than in controls. Anti-Apo A-I and anti-HDL levels, but not anti-CRP levels, were higher in patients with persistently high disease activity than in those with low disease activity. Mean levels of the 3 autoantibodies in patients who had experienced CVD events lay between the mean levels in the high and low disease activity groups. Only levels of anti-Apo A-I were significantly higher in samples obtained from individual patients during disease flares than in samples obtained during disease quiescence. In the lupus nephritis patients, anti-Apo A-I and anti-HDL levels correlated with serum levels of high avidity IgG anti-double-stranded DNA. CONCLUSION:Persistent disease activity is associated with a significant increase in IgG anti-Apo A-I and anti-HDL in patients with SLE.
Are oxidized low-density lipoprotein and C-reactive protein markers of atherosclerosis in nephrotic children?
Rybi-Szumińska A,Wasilewska A,Michaluk-Skutnik J,Osipiuk-Remża B,Fiłonowicz R,Zając M
Irish journal of medical science
BACKGROUND:Lipid disorders are known to be linked to disturbance in oxidative reactions and play an important role in the progression and complications of idiopathic nephrotic syndrome (INS). AIMS:The aim of this study was to assess oxidized low-density lipoprotein (oxLDL), high-sensitive C-reactive protein (hs-CRP) serum concentrations and other parameters of lipid metabolism in children with INS during relapse and remission of proteinuria. METHODS:The examination was performed on 23 children and adolescents diagnosed with INS. Reference group consisted of 22 participants. The study was carried out twice: in the relapse of INS (A) and in remission of proteinuria during glucocorticoid treatment (B). RESULTS:OxLDL was higher in INS patients, in both examinations when compared with reference participants. hs-CRP showed no differences between nephrotic and healthy children. We found higher concentration of oxLDL in children, who where frequent relapsers. Cholesterol, triglycerides/high density lipoprotein cholesterol and platelets were higher in INS patients (both A and B) in comparison with healthy children. CONCLUSIONS:We observed presence of pro-atherogenic lipid profile in INS. Elevation of oxLDL may reflect increased oxidative stress and higher risk of atherosclerosis in INS, therefore it seems to be relevant to find patients of risk of atherosclerosis to consider lipid lowering treatment with antioxidants.
Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial.
Ridker Paul M,MacFadyen Jean G,Glynn Robert J,Bradwin Gary,Hasan Ahmed A,Rifai Nader
European heart journal
AIMS:In epidemiologic cohorts initiated >30 years ago, inflammatory biomarkers, such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were shown to independently predict future cardiovascular events with a magnitude of effect comparable to that of low-density lipoprotein cholesterol (LDLC). Whether aggressive contemporary therapy for atherosclerosis has altered these relationships is unknown yet has major implications for future drug development. METHODS AND RESULTS:Interleukin-6, hsCRP, and LDLC were measured at baseline in up to 4168 North American patients enrolled in the contemporary Cardiovascular Inflammation Reduction Trial with prior myocardial infarction or multivessel coronary disease who additionally had diabetes or metabolic syndrome and were followed for a period of up to 5 years for incident major recurrent cardiovascular events and all-cause mortality. Three-quarters of the cohort were previously revascularized and the great majority was taking statins, angiotensin blocking agents, beta-blockers, and antithrombotic agents. Participants were randomly allocated to low-dose methotrexate 15 mg weekly or to placebo. Randomized use of methotrexate had no effect on event rates nor plasma levels of IL-6, hsCRP, or LDL over time. Yet, baseline levels of IL-6, hsCRP, and LDLC were all predictors of major recurrent cardiovascular events; adjusted hazard ratios [HR; 95% confidence interval (CI)] for the lowest to highest baseline quartiles of IL-6 were 1.0 (referent), 1.66 (1.18-2.35), 1.92 (1.36-2.70), and 2.11 (1.49-2.99; P < 0.0001), while adjusted HRs for increasing quartiles of hsCRP were 1.0 (referent), 1.28 (0.92-1.79), 1.73 (1.25-2.38), and 1.79 (1.28-2.50; P < 0.0001) and adjusted HRs for increasing quartiles of LDLC were 1.0 (referent), 1.12 (0.78-1.62), 1.25 (0.87-1.79), and 2.38 (1.72-3.30; P < 0.0001). Effect estimates were not statistically different in these analyses for comparisons between IL-6, hsCRP, or LDLC, although IL-6 was the strongest predictor of all-cause mortality. The highest absolute risks were observed among those with elevated levels of both cholesterol and inflammation [HR 6.4 (95% CI 2.9-14.1) for those in the top quartiles of baseline IL-6 and LDLC, HR 4.9 (95% CI 2.6-9.4) for those in the top quartiles of baseline hsCRP and LDLC, both P < 0.0001]. CONCLUSION:Despite aggressive contemporary secondary prevention efforts, the relationships between inflammation, cholesterol, and cardiovascular risk are largely unchanged from those described two decades ago. These data are consistent with the hypothesis that future treatments for atherosclerosis may require a combination of inflammation inhibition and additional cholesterol reduction. CLINICAL TRIAL:ClinicalTrials.gov NCT01594333.
Analysis and modelling of cholesterol and high-density lipoprotein cholesterol changes across the range of C-reactive protein levels in clinical practice as an aid to better understanding of inflammation-lipid interactions.
Johnsson Hanna,Panarelli Maurizio,Cameron Allan,Sattar Naveed
Annals of the rheumatic diseases
OBJECTIVES:Raised total cholesterol (TC) and reduced high-density lipoprotein (HDL) cholesterol levels are established cardiovascular disease (CVD) risk factors. However, in autoimmune conditions the lipid-CVD association appears paradoxical, with inflammation as a potential confounding factor. We therefore sought to model the relationship between systemic inflammatory illness and lipid levels using C-reactive protein (CRP) as the prototypical marker of inflammation. Our hypothesis was that there would be an inverse association between raised CRP levels and both TC and HDL-cholesterol levels. METHODS:Results from samples analysed simultaneously for CRP and lipids in a 6-month period were collected retrospectively from a large city hospital laboratory database that collates results from both primary and secondary care. The relationships between CRP and lipids were determined using graphical techniques and empirical, non-parametric, best fit models. RESULTS:A total of 11 437 blood samples was included. We identified a significant (p<0.001) biphasic relationship between TC and CRP: TC increased within the healthy CRP range of less than 5 mg/l, but decreased with CRP levels above 10 mg/l. The two effects approximately cancelled each other out in the intermediate CRP range of 5-10 mg/l. There was an inverse relationship between HDL-cholesterol and CRP. CONCLUSIONS:Lipid levels change significantly during inflammatory illness in a population with both acute and chronic conditions. These results provide a strong epidemiological basis for the better understanding of lipid changes in inflammatory conditions and with anti-inflammatory therapies.
Inflammation level and renal function injury in antineutrophil cytoplasmic antibody-associated vasculitis: a correlation with low albumin and high-density lipoprotein.
Zeng Tingting,Tian Yongjian,Tan Liming,Wu Yang,Yu Jianlin,Huang Jiayi,Pei Zihuang
Biomarkers in medicine
To explore the correlation of inflammation level and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with Alb and HDL. Serum levels of Alb and HDL were measured, with AAV patients being grouped according to serum Alb and HDL levels, and indicators reflecting inflammation and renal injury were compared. Serum levels of creatinine (Cr), uric acid and CRP and renal involvement rates were higher in lower Alb patients; Cr, CRP, renal and cardiovascular involvement rates in lower HDL patients were higher. Alb and HDL were negatively correlated with CRP and erythrocyte sedimentation rate. Serum Alb and HDL were good indictors for disease monitoring in AAV.
Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein.
Corsetti James P,Sparks Charles E,James Richard W,Bakker Stephan J L,Dullaart Robin P F
Journal of clinical medicine
Paroxonase-1 (PON1) is a key enzyme that inhibits low-density lipoprotein oxidation and consequently atherogenesis. Here, we assessed whether low serum PON1 activity associates with incident cardiovascular disease (CVD) in subjects with high levels of high-density cholesterol (HDL-C) and C-reactive protein (CRP), a marker of low-grade systemic inflammation. Cox proportional-hazards modeling of incident CVD risk (11 years mean follow-up) adjusted for relevant clinical and biomarker covariates was performed on a population-based study (N = 7766) stratified into three groups: low CRP-(LR; event rate 4.9%); low HDL-C/high CRP-(HR1; event rate 14.4%); and high HDL-C/high CRP-(HR2; event rate 7.6%). Modeling results for PON1 activity in HR2 were significant and robust (hazard ratio/SD unit-0.68, 95% CI 0.55-0.83, = 0.0003), but not so for LR and HR1. Analyses in HR2 of the interaction of PON1 with HDL-C, apoA-I, apoA-II, and apoE levels were significant only for PON1 with apoE (hazard ratio-1.77, 95% CI 1.29-2.41, = 0.0003). Subsequent subgroup analysis revealed inverse risk dependence for apoE at low PON1 levels. In conclusion, in a population-based study of subjects with concurrently high HDL-C and CRP levels, low serum PON1 activity associates with incident CVD risk with risk accentuated at low apoE levels.
Impact of Combined C-Reactive Protein and High-Density Lipoprotein Cholesterol Levels on Long-Term Outcomes in Patients With Coronary Artery Disease After a First Percutaneous Coronary Intervention.
Ogita Manabu,Miyauchi Katsumi,Tsuboi Shuta,Shitara Jun,Endo Hirohisa,Wada Hideki,Doi Shinichiro,Naito Ryo,Konishi Hirokazu,Dohi Tomotaka,Kasai Takatoshi,Tamura Hiroshi,Okazaki Shinya,Suwa Satoru,Daida Hiroyuki
The American journal of cardiology
Cardiovascular risk persists despite intensive low-density lipoprotein cholesterol (LDL-C) reduction using statins. High-density lipoprotein (HDL-C) is inversely associated with coronary artery disease (CAD) that is independent of LDL-C levels. C-reactive protein (CRP) is an established marker of inflammation that can impair the protective function of HDL-C: however, the impact of inflammation on the association between HDL-C and long-term outcomes in patients with CAD under statin therapy remains uncertain. We prospectively enrolled 3,507 consecutive patients with CAD who underwent a first percutaneous coronary intervention (PCI) from 1997 to 2011 at our institution. We stratified 1,682 patients (48%) who had been treated with statin at the time of PCI into 4 groups according to HDL-C levels (cutoffs of 40 and 50 mg/dl for men and women, respectively) and a CRP cutoff of 2 mg/dl: (1) high HDL-C/low CRP, (2) high HDL-C/high CRP, (3) low HDL-C/low CRP, and (4) low HDL-C/high CRP comparing the rates of all-cause death among them. The median follow-up period was 1,985 days (interquartile range 916 to 3,183 days). During this period, 197 patients (11.7%) died because of cardiac death (n = 58), carcinoma (n = 61), stroke (n = 10), and other causes (n = 69). The rates of all-cause death significantly differed among the groups (log-rank test, p <0.0001). In multivariate Cox hazard regression analyses, low HDL-C with high CRP levels remained significantly associated with a higher rate of all-cause death even after adjustment for other co-variates (hazard ratio 2.38, 1.59 to 3.61, p <0.0001). Low HDL-C together with elevated CRP levels is significantly associated with long-term outcomes in patients who received statin therapy after PCI.
The Ratios of Triglycerides and C-reactive protein to High density-lipoprotein -cholesterol as valid biochemical markers of the Nascent Metabolic Syndrome.
Jialal Ishwarlal,Adams-Huet Beverley
: Metabolic syndrome (MetS), a cardiometabolic cluster, is a major global problem. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) is a good biomarker of MetS in certain populations C-reactive protein (CRP) has also been also shown to be a biomarker of MetS. Since CRP captures inflammation, we compared the ratios of TG to HDL-C and CRP to HDL-C in patients with nascent MetS.: Patients with MetS ( = 58) and matched controls ( = 44) were recruited. Fasting blood samples were obtained for routine laboratories, insulin, and adipokines. TG and CRP ratios to HDL-C were calculated. Data were analyzed statistically.: Both the TG to HDL-C and CRP to HDL-C ratios were significantly increased in MetS and both increased with increasing severity of MetS. Whilst both correlated with cardiometabolic features and insulin resistance, only the CRP to HDL-C ratio correlated significantly with adiponectin and leptin. Receiver operating characteristic curve analysis showed that both ratios showed excellent discrimination for MetS with no significant differences between ratios.: Thus both the TG to HDL-C and CRP to HDL-C ratios are significantly increased in patients with nascent MetS and appear to be valid biomarkers of MetS. However, these preliminary findings with CRP: HDL-C need confirmation in large prospective studies and could have important implications for assessing cardiometabolic risk in African Americans, an under-served population.
High-Sensitivity C-Reactive Protein Discordance With Atherogenic Lipid Measures and Incidence of Atherosclerotic Cardiovascular Disease in Primary Prevention: The ARIC Study.
Quispe Renato,Michos Erin D,Martin Seth S,Puri Rishi,Toth Peter P,Al Suwaidi Jassim,Banach Maciej,Virani Salim S,Blumenthal Roger S,Jones Steven R,Elshazly Mohamed B
Journal of the American Heart Association
Background Inflammation is an independent causal risk factor for atherosclerotic cardiovascular diseases (ASCVDs). However, whether hsCRP (high-sensitivity C-reactive protein) is prognostic across various levels of atherogenic lipid measures such as low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and total cholesterol/high-density lipoprotein cholesterol in primary prevention is unknown. Methods and Results We studied 9748 ARIC (Atherosclerosis Risk in Communities) study participants who were free of ASCVD at baseline (visit 4, 1996-1998) and had measurements of lipids, apolipoprotein B, and hsCRP. We used multivariable adjusted Cox models to estimate the risk of incident ASCVD events associated with hsCRP levels (less than/greater than or equal to median) in individuals where triple lipid measures combined (low-density lipoprotein cholesterol + non-high-density lipoprotein cholesterol + apolipoprotein B) or quadruple measures combined [triple + total cholesterol/high-density lipoprotein cholesterol] were less than versus greater than or equal to median cut points. Mean age of participants was 62.6±5.6 years; 59% women, 22% black. There were 1574 ASCVD events over median (interquartile range) follow-up of 18.4 (12.8-19.5) years, and discordance between hsCRP and lipid measures was prevalent in 50% of the population. hsCRP greater than or equal to median (2.4 mg/L), compared with less than median, was associated with an increased risk of ASCVD in individuals with less than median levels of the triple (adjusted hazard ratio, 1.33; 95% CI, 1.09-1.60) and quadruple (adjusted hazard ratio,1.47; 95% CI, 1.18-1.85) lipid measures. Such increased risk was consistent among individuals with low (<7.5%) or high (≥7.5%) estimated risk by the pooled cohort equation. There were no interactions by sex, diabetes mellitus, or statin use. Conclusions Our findings suggest that inflammation is independently associated with ASCVD regardless of atherogenic lipid levels and pooled cohort equation risk score in individuals without known ASCVD.
Additive Value of High-Density Lipoprotein Cholesterol and C-Reactive Protein Level Assessment for Prediction of 2-year Mortality After Transcatheter Aortic Valve Implantation.
Zieliński Kamil,Kalińczuk Łukasz,Chmielak Zbigniew,Mintz Gary S,Dąbrowski Maciej,Pręgowski Jerzy,Świerczewski Michał,Kowalik Ilona,Demkow Marcin,Hryniewiecki Tomasz,Michałowska Ilona,Witkowski Adam
The American journal of cardiology
Available prediction models are inaccurate in elderly who underwent transcatheter aortic valve implantation (TAVI). The aim of present study was to analyze the separate and combined prognostic values of baseline HDL-C and C-reactive protein (CRP) levels in patients treated successfully with TAVI who had complete 2-year follow-up. We analyzed 334 patients treated with TAVI from 01/2010 to 07/2017 who had measurements of HDL-C and CRP on admission or during qualification for the procedure. Baseline HDL-C ≤46 mg/dl (areas under the curve [AUC] = 0.657) and CRP ≥0.20 mg/dl (AUC = 0.634) were predictive of 2-year mortality. After stratification with both cutoffs, patients with low HDL-C and concomitant high CRP most often had LVEF ≤50% and were high risk as per EuroSCORE II. Those with isolated CRP elevation had the lowest frequency of LVEF ≤50%, but more sarcopenia (based on psoas muscle area). After adjustment in the multivariate analysis for other identified predictors including EuroSCORE II and statin therapy, isolated HDL-C ≤46 mg/dl (identified in 40 patients) and isolated CRP ≥0.20 mg/dl (n = 109) were both independent predictors of 2-year mortality (hazard ratio [HR] = 2.92 and HR = 2.42, respectively) compared with patients with both markers within established cutoffs (n = 105) who had the lowest 2-year mortality (9.5%). Patients with both markers exceeding cutoffs (n = 80) had the highest risk (HR = 4.53) with 2-year mortality of 42.5%. High CRP was associated with increased mortality within the first year of follow-up, whereas low HDL-C increased mortality in the second year. The combination of both markers with EuroSCORE II enhanced mortality prediction (AUC = 0.697). In conclusion, low baseline HDL-C and high CRP jointly contribute to the prediction of increased all-cause mortality after TAVI.
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.
Comparison of the Value of Neutrophil to High-Density Lipoprotein Cholesterol Ratio and Lymphocyte to High-Density Lipoprotein Cholesterol Ratio for Predicting Metabolic Syndrome Among a Population in the Southern Coast of China.
Diabetes, metabolic syndrome and obesity : targets and therapy
BACKGROUND:This study aimed to determine the optimal cutoff values and evaluate the associations of neutrophil to high-density lipoprotein cholesterol ratio (NHR) and lymphocyte to high-density lipoprotein cholesterol ratio (LHR) with metabolic syndrome (MetS), stratified by sex. METHODS:A large-scale cross-sectional survey was conducted among 1401 adults from January to April 2018 in six communities in Wanzhai Town, Zhuhai City, on the southern coast of China. Receiver operating characteristics (ROC) analyses and logistic regression analysis were conducted to assess the optimal cutoff and value of NHR and LHR for predicting MetS. RESULTS:Hematological parameters showed the correlation with the occurrence of MetS (red blood cells, hemoglobin, and white blood cells and subtypes). Binomial logistic regression analysis found that LHR (OR: 3.671; 95% CI: 2.385-5.651; <0.001) and NHR (OR: 1.728; 95% CI: 1.353-2.207; <0.001) can predict MetS in females, independent of confounding factors. Although LHR (OR: 1.571; 95% CI: 1.001-2.468; =0.05) and NHR (OR: 1.163; 95% CI: 0.909-1.48; <0.01) were independent risk factors for MetS in males after adjustment for age, current smoking, current alcohol use, physical activity, educational attainment, waist circumference, systolic pressure, diastolic pressure and hypersensitive C-reactive protein (hs-CRP), when further adjusted for fasting plasma glucose level, LHR and NHR, both lost their independence. ROC curves showed that LHR had the highest AUC for predicting MetS in females and NHR had the highest AUC in males. The cutoff points of LHR and NHR were 1.36 and 2.31 in females, and 1.96 and 3.38 in males. CONCLUSION:LHR and NHR may become valuable makers and have strong predictive power for predicting MetS, especially in females.
Association of monocyte to high-density lipoprotein cholesterol ratio with carotid artery intima-media thickness in patients with systemic lupus erythematosus.
Wang Qian,Meng Yan,Cao Wenyan,Du Wenjing,Liu Yumei,Yan Yi,Luo Li,Ma Xiumin
Biomarkers in medicine
AIM:The purpose of this study was to evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio (MHR) and carotid atherosclerostic plaque in patients with systemic lupus erythematosus (SLE). METHODS:A total of 214 SLE patients were divided into two groups according to the results of ultrasonic examination: carotid arterial atherosclerotic plaque groups and noncarotid arterial atherosclerosis groups. RESULTS:The values of monocyte to high-density lipoprotein-cholesterol ratio (MHR) increase in carotid arterial atherosclerotic plaque groups compared with noncarotid arterial atherosclerosis groups (0.32 ± 0.18 vs 0.26 ± 0.15; p = 0.015). There was a significant correlation between MHR and carotid artery intima-media thickness (r = 0.228; p = 0.001) in patients with SLE. CONCLUSION:Our study suggests that the values of MHR could be a marker to assess carotid artery intima-media thickness in patients with SLE.
Increases in uric acid and monocyte-high-density lipoprotein ratio as possible atherosclerotic indicators in acne patients using isotretinoin.
Metin Nurcan,Turan Çağrı
Journal of cosmetic dermatology
PURPOSE:We aimed to reveal the relationship of serum uric acid (SUA) with monocyte-high-density lipoprotein ratio (MHR) and other inflammatory markers in acne patients before and after isotretinoin treatment. In this way, we can try to shed light on the relationship between isotretinoin treatment and atherosclerosis. METHODS:Two hundred twenty-four acne patients who administered isotretinoin (0.5-1 mg/kg/day) were enrolled in the study. In the pretreatment phase and 3 months after treatment, MHR, SUA, mean platelet volume, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, monocyte-lymphocyte ratio, serum triglyceride, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels of the patients were analyzed. RESULTS:Compared to the pretreatment phase, three months after treatment, there was a statistically decrease in neutrophil count and an increase in lymphocyte count (p: 0.002, p: 0.011, respectively). Accordingly, there was a statistically significant decrease in NLR (p: 0.001). It was noteworthy that MHR and SUA levels increased significantly (p: 0.042, p: 0.010, respectively) and there was a positive correlation between SUA level and MHR (r: 0.212, p: 0.012). Serum total cholesterol, LDL, and triglyceride levels increased and HDL levels decreased significantly after treatment (p: 0.001). CONCLUSION:This study contributes to the comprehension of the relationship between isotretinoin treatment and atherosclerosis, which has been frequently reported in the literature. It was thought that the isotretinoin-induced SUA increase might be related to dyslipidemia. Isotretinoin may initiate the atherosclerotic process in vascular endothelial and smooth muscles, with SUA increase and HDL decrease. An increase in MHR is also an inflammatory marker indicating this process.
Elevated Monocyte to High-Density Lipoprotein Cholesterol Ratio and Endothelial Dysfunction in Behçet Disease.
Acikgoz Nusret,Kurtoğlu Ertuğrul,Yagmur Julide,Kapicioglu Yelda,Cansel Mehmet,Ermis Necip
Behçet disease (BD) is a multisystemic disorder characterized by endothelial dysfunction and inflammation. Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a recently emerged indicator of inflammation and oxidative stress. Sixty patients with BD and 50 control individuals were included to investigate the relationship between MHR and endothelial dysfunction. Endothelial function was assessed by flow- and nitroglycerin-mediated dilatation technique (FMD and NMD, respectively). Serum high-sensitivity C-reactive protein (hsCRP) levels were measured in all study participants. The MHR and hsCRP levels were significantly higher in patients with active BD than in controls. Brachial artery FMD was significantly lower in patients with active BD than in controls. Brachial artery NMD was similar between groups. There was a strong inverse correlation between MHR and FMD and a strong positive correlation between MHR and serum hsCRP levels. Thus, elevated MHR may be a useful marker reflecting impaired endothelial function and systemic inflammation in patients with BD.
Monocyte to high-density lipoprotein cholesterol ratio in patients with diabetes mellitus and diabetic nephropathy.
Karatas Ahmet,Turkmen Ercan,Erdem Emre,Dugeroglu Harun,Kaya Yasemin
Biomarkers in medicine
AIM:We investigated the relationship of monocyte to high-density lipoprotein cholesterol ratio (MHR) with diabetes mellitus and diabetic nephropathy. METHODS & RESULTS:A total of 220 diabetes mellitus patients and 70 healthy controls were enrolled. There was no difference in an MHR between normoalbuminuric diabetic patients and the healthy controls. The MHR in patients with diabetic nephropathy was significantly higher than that of both the normoalbuminuric diabetic patients and the healthy controls. There was a significant positive correlation between urine albumin to creatinine ratio and the MHR. In multivariate linear regression analysis, the MHR was independently correlated with urine albumin to creatinine ratio. Conclusion: An increased MHR may be a biomarker for diabetic nephropathy.
Correlation between high density lipoprotein and monocyte subpopulations among stable coronary atherosclerotic heart disease patients.
Yang Rong-Hai,Liu Ying-Feng,Wang Xue-Jun,Liang Jian-Guang,Liu Jia-Chao
International journal of clinical and experimental medicine
High density lipoprotein (HDL) is a structurally and functionally heterogeneous molecular particle whose function is unclear in atherosclerosis at present. Studies show that small HDL functional imbalance may exist in Coronary Atherosclerotic Heart Disease (CAD) patients. Monocyte is considered to play an important role in atherosclerosis, in accordance with the expression of superficial CD14 and CD16, it can be divided into three subpopulations. The purpose of this study was to explore the relation between HDL and monocyte subpopulations among CAD patients. We report 90 cases of stable CAD patients and define the monocyte subpopulations as classical monocyte (CD14++CD16-; CM), intermediate monocyte (CD14+CD16+; IM), and non-classical monocyte (CD14+CD16++; NCM); HDL group is measured by polyacrylamide gel electrophoresis. The results indicated that the small HDL in blood serum has a correlation with proinflammatory NCM in circulation but a negative correction with CM and no relationship with diabetes, saccharify hemoglobin, hypertension, smoking history and taking dose of statins drugs and severity of disease. In conclusion, this study primarily confirms that micromolecule HDL level correlates with the increase of non-classical monocyte subpopulations and decrease of classical monocyte quantity. Thus demonstrates the proinflammatory correlation between micromolecule HDL and internal immunity in the development of stable atherosclerosis.
The relationship between monocyte to high-density lipoprotein cholesterol ratio and diabetic nephropathy.
Pakistan journal of medical sciences
OBJECTIVE:This study aims to investigate the relationship of monocyte to high-density lipoprotein cholesterol ratio (MHR) with diabetes mellitus (DM) and diabetic nephropathy. METHODS:This study included 262 Type-2 diabetes mellitus patients, of which 60 had diabetic nephropathy and 202 did not have diabetic nephropathy who presented to the internal diseases polyclinic at Firat University Medical Faculty Hospital between May 2018 and October 2018 and 50 healthy control subjects. A retrospective scan of patient files was conducted and information relevant to nephropathy such as hemoglobin, glycated hemoglobin levels (HbA1c), hematocrit count (HCT), monocyte count, LDL, HDL, triglyceride levels, and microvascular complications were acquired. RESULTS:We determined MHR values as 11.9±5.5 and 8.4±2.9 respectively for the diabetic and healthy groups. There was a statistically significant difference between the two groups in terms of MHR, with a positive correlation between diabetes and MHR (< 0.001; r: 0.241). Moreover, glucose, HDL, and triglyceride levels were different between the two groups with statistical significance (respectively, p< 0.001; p< 0.001; p< 0.001). Our study found higher MHR levels for patients with diabetic nephropathy compared to those without diabetic nephropathy (respectively, 17.1±7.9 and 10.3±3.3) and determined statistical significance and a negative correlation (p< 0.001; r: -0.512). CONCLUSION:Our results suggest that an elevated MHR can be a biomarker for diabetic nephropathy, allowing the detection of diabetic nephropathy with simple and inexpensive laboratory tests.
Monocyte High Density Lipoprotein Cholesterol Ratio as a New Prognostic Factor for Mesenteric Embolism.
Kuvvetli Adnan,Avci Begum Seyda
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP
OBJECTIVE:To determine the effectiveness of the ratio of monocyte count to high density lipoprotein cholesterol in predicting in-hospital mortality. STUDY DESIGN:Descriptive study. PLACE AND DURATION OF STUDY:Intensive Care Unite, Adana Numune Research and Training Hospital, Turkey, from January 2018 to December 2019. METHODOLOGY:Patients admitted to the intensive care unit with the diagnosis of mesenteric embolism were included in the study. Monocyte count and high-density lipoprotein cholesterol (HDL) values were determined. Monocyte HDL Ratio (MHR) values of the patients were calculated. SPSS 26 package programme was used to investigate the effectiveness of MHR in predicting mortality. RESULTS:The mean age of the 81 patients was 69.9 ±10.6 years. In the group with mortality, the number of monocytes and MHR were significantly higher than the group without mortality (p<0.05). In the mortality group, HDL value was significantly lower (p<0.05) than the non-mortality group. Sensitivity of the MHR cutoff value of 19 was 81.8%, positive predictive value was 96.4%, specificity value was 97.9%, negative predictive value was 88.7%. CONCLUSION:For patients diagnosed with acute mesenteric embolism, the use of predictors in terms of mortality estimation is very important for the faster implementation of treatment modalities. MHR value can be used as a strong predictor. Key Words: Mesenteric embolism, Monocyte, HDL cholesterol, MHR, Mortality.
Relationship between non-high-density lipoprotein cholesterol/apolipoprotein A-I and monocyte/high-density lipoprotein cholesterol ratio and coronary heart disease.
Li Ya,Li Shu,Ma Yulin,Li Jialing,Lin Mingying,Wan Jing
Coronary artery disease
OBJECTIVE:To investigate the association between non-high-density lipoprotein cholesterol/apolipoprotein A-I and monocyte/high-density lipoprotein cholesterol ratio and degree of coronary artery stenosis proven by coronary angiography. METHODS:A total of 1867 patients were enrolled into this study and analyzed retrospectively. Three hundred eighty-five non-coronary artery disease hospitalized patients were selected as control group, 1482 patients diagnosed as coronary artery disease were classified into three subgroups according to the tertiles of their SYNTAX score. We compared the level of non-high-density lipoprotein cholesterol/apolipoprotein A-I and monocyte/high-density lipoprotein cholesterol ratio among the three subgroups. The Spearman correlation was used to analyze the correlation between non-high-density lipoprotein cholesterol/apolipoprotein A-I and monocyte/high-density lipoprotein cholesterol ratio and SYNTAX, logistic regression was used for analyzing independent predictors of coronary artery disease. RESULTS:The level of non-high-density lipoprotein cholesterol/apolipoprotein A-I and monocyte/high-density lipoprotein cholesterol ratio was higher in coronary artery disease group compared with non-coronary artery disease group (P < 0.01). The Spearman correlation analysis showed that non-high-density lipoprotein cholesterol/apolipoprotein A-I and monocyte/high-density lipoprotein cholesterol ratio were significantly correlated with SYNTAX score (r = 0.081, P < 0.001; r = 0.216, P < 0.001). In multivariate logistic regression analysis showed that non-high-density lipoprotein cholesterol/apolipoprotein A-I and monocyte/high-density lipoprotein cholesterol ratio were independent predictors of coronary artery disease (odds ratio = 3.645, 95% confidence interval, 1.267-10.486; OR = 2.096, 95% confidence interval, 1.438-3.054). CONCLUSION:Non-high-density lipoprotein cholesterol/apolipoprotein A-I and monocyte/high-density lipoprotein cholesterol ratio were associated with the severity of coronary artery lesions, which can be used as a biomarker for the evaluation of severity of coronary artery disease.
Association between Monocyte Count and Risk of Incident CKD and Progression to ESRD.
Bowe Benjamin,Xie Yan,Xian Hong,Li Tingting,Al-Aly Ziyad
Clinical journal of the American Society of Nephrology : CJASN
BACKGROUND AND OBJECTIVES:Experimental evidence suggests a role for monocytes in the biology of kidney disease progression; however, whether monocyte count is associated with risk of incident CKD, CKD progression, and ESRD has not been examined in large epidemiologic studies. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS:We built a longitudinal observational cohort of 1,594,700 United States veterans with at least one eGFR during fiscal year 2004 (date of last eGFR during this period designated time zero) and no prior history of ESRD, dialysis, or kidney transplant. Cohort participants were followed until September 30, 2013 or death. Monocyte count closest to and before time zero was categorized in quartiles: quartile 1, >0.00 to ≤0.40 thousand cells per cubic millimeter (k/cmm); quartile 2, >0.40 to ≤0.55 k/cmm; quartile 3, >0.55 to ≤0.70 k/cmm; and quartile 4, >0.70 k/cmm. Survival models were built to examine the association between monocyte count and risk of incident eGFR<60 ml/min per 1.73 m, risk of incident CKD, and risk of CKD progression defined as doubling of serum creatinine, eGFR decline ≥30%, or the composite outcome of ESRD, dialysis, or renal transplantation. RESULTS:Over a median follow-up of 9.2 years (interquartile range, 8.3-9.4); in adjusted survival models, there was a graded association between monocyte counts and risk of renal outcomes. Compared with quartile 1, quartile 4 was associated with higher risk of incident eGFR<60 ml/min per 1.73 m (hazard ratio, 1.13; 95% confidence interval, 1.12 to 1.14) and risk of incident CKD (hazard ratio, 1.15; 95% confidence interval, 1.13 to 1.16). Quartile 4 was associated with higher risk of doubling of serum creatinine (hazard ratio, 1.22; 95% confidence interval, 1.20 to 1.24), ≥30% eGFR decline (hazard ratio, 1.18; 95% confidence interval, 1.17 to 1.19), and the composite renal end point (hazard ratio, 1.19; 95% confidence interval, 1.16 to 1.22). Cubic spline analyses of the relationship between monocyte count levels and renal outcomes showed a linear relationship, in which risk was higher with higher monocyte count. Results were robust to changes in sensitivity analyses. CONCLUSIONS:Our results show a significant association between higher monocyte count and risks of incident CKD and CKD progression to ESRD.
Monocyte/HDL Ratio and Lymphocyte/Monocyte Ratio in Patients with Pseudoexfoliation Syndrome.
Mirza Enver,Oltulu Refik,Katipoğlu Zeynep,Mirza Günsu Deniz,Özkağnıcı Ahmet
Ocular immunology and inflammation
To evaluate the association between monocyte count/high-density lipoprotein (HDL) ratio (MHR) and lymphocyte count/monocyte count ratio (LMR) with pseudoexfoliation syndrome (PEXS) and pseudoexfoliation glaucoma (PEXG). A total of 63 participants included in the study. Participants were divided into three groups. Twenty-one patients with PEXS regarded as group 1, 21 patients with PEXG regarded as group 2 and 21 participants without PEXS or PEXG regarded as the control group. Blood parameters were accessed from file records and database retrospectively. The mean MHRs were significantly higher in group 1 and group 2 ( = 0.003, = 0.036) than the control group, whereas there was no difference between group 1 and group 2 ( = 0.686). The mean LMRs were lower in group 1 and group 2 than the control group but the difference was insignificant ( = 0.232). We found that there is an association between higher MHR and lower LMR with PEXS.
The Predictive Role of Lymphocyte-to-Monocyte Ratio in Acute Kidney Injury in Acute Debakey Type I Aortic Dissection.
Ma Xiaochun,Chen Shanghao,Yun Yan,Zhao Diming,Li Jinzhang,Wu Zezhong,Liu Yanwu,Shen Hechen,Ma Huibo,Wang Zhengjun,Zou Chengwei,Zhang Haizhou
Frontiers in surgery
The post-operative acute kidney injury (AKI) represents a common complication in the Acute Debakey Type I Aortic Dissection (ADTIAD) and predicts a poorer prognosis. The clinical evidence is scarce supporting the predictive value of the pre-operative lymphocyte-to-monocyte ratio (LMR) in post-operative AKI in ADTIAD. In this retrospective cohort study, 190 consecutive patients with ADTIAD enrolled for surgical treatment between January 1, 2013, and December 31, 2018. The diagnosis of AKI followed the Kidney Disease: Improving Global Outcomes guidelines (KDIGO). Pre-operative LMR and other possible risk factors were analyzed for their prognostic value in the post-operative AKI in ADTIAD. The subjects were assigned to the low-LMR and high-LMR groups according to the median value of pre-operative LMR. For post-operative AKI, the incidence and the severity in the low-LMR group were statistically different from that of the high-LMR group. Besides, the lower LMR was statistically associated with the more extended ICU stay and intubation time and higher incidences of ischemic stroke and in-hospital mortality. Additionally, in the multivariable analysis, the pre-operative LMR was an independent predictor for post-operative AKI in ADTIAD. A predictive model for post-operative AKI in ADTIAD was established incorporating LMR. LMR is an independent prognostic indicator incorporated into the predictive model with other risk factors to predict the post-operative AKI in ADTIAD.
Monocyte count/HDL cholesterol ratio and cardiovascular events in patients with chronic kidney disease.
Kanbay Mehmet,Solak Yalcin,Unal Hilmi Umut,Kurt Yasemin Gulcan,Gok Mahmut,Cetinkaya Hakki,Karaman Murat,Oguz Yusuf,Eyileten Tayfun,Vural Abdulgaffar,Covic Adrian,Goldsmith David,Turak Osman,Yilmaz Mahmut Ilker
International urology and nephrology
BACKGROUND AND AIM:Previous studies showed that renal dysfunction was associated with both a reduction in serum high-density lipoprotein (HDL) cholesterol concentration and increased circulating monocyte count. We aimed to investigate the effect of circulating monocyte to serum HDL cholesterol ratio (M/H ratio) on fatal and composite cardiovascular events, in an observational cohort study of chronic kidney disease (CKD) patients. MATERIALS AND METHODS:A total of 340 subjects with stage 1-5 CKD were followed for a mean follow-up period of 33 (range 2-44) months and assessed for fatal and nonfatal CV events. M/H ratio was calculated for all patients. All-cause mortality and CVE were also analyzed in relation to M/H ratio. RESULTS:Monocyte/HDL cholesterol ratio was negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.43, P < 0.001). Notably, both fatal and combined fatal and nonfatal cardiovascular events were more common in patients having a M/H ratio in the third tertile was associated with a hazard ratio of 2.24 and 4.91, respectively, for fatal and composite cardiovascular events compared to being in the first tertile. CONCLUSION:Monocyte/HDL cholesterol ratio was increased with decreasing eGFR in predialytic CKD patients. Most importantly, we report for the first time that an increased M/H ratio was cross-sectionally associated with a worse cardiovascular profile and arose as independent predictors of major cardiovascular events during follow-up.
Monocyte to high density lipoprotein ratio in patients with acute kidney injury after cardiac surgery.
BACKGROUND:The Monocyte to high density lipoprotein ratio (MHR) has been postulated as a novel parameter associated with adverse renal and cardiovascular outcomes. In this study we investigated the association of MHR with cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS:In this retrospective study, we analyzed the data pertaining to 1505 patients undergoing cardiopulmonary bypass (CPB) surgery. The CSA-AKI, which was defined using Kidney Disease Improving Global Outcomes criteria. Concurrently, a retrospective scan of patient files was conducted and information relevant to nephropathy such as the level of their serum creatinine (SCr), Blood urea nitrogen (BUN), uric acid (UA), serum cystatin C (Cys-C), total cholesterol (TC), triglycerides (TG), glucose and MHR, ejection fraction, CPB duration time, and other indicators. RESULTS:About 1505 patients were studied of whom 195 developed AKI. MHR was significantly higher in the AKI patients (p = 0.001). In multivariate logistic regression analysis, MHR, UA, Cys-C, age, glucose, and history of chronic kidney disease or hypertension were independently correlated with CSA-AKI. CONCLUSIONS:As a laboratory index, the elevated MHR is convenient, independent, and a useful predictor for CSA-AKI.
The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia-reperfusion injury.
Li Li,Huang Liping,Sung Sun-Sang J,Vergis Amy L,Rosin Diane L,Rose C Edward,Lobo Peter I,Okusa Mark D
Chemokines and their receptors such as CCR2 and CX3CR1 mediate leukocyte adhesion and migration into injured tissue. To further define mechanisms of monocyte trafficking during kidney injury we identified two groups of F4/80-positive cells (F4/80(low) and F4/80(high)) in the normal mouse kidney that phenotypically correspond to macrophages and dendritic cells, respectively. Following ischemia and 3 h of reperfusion, there was a large influx of F4/80(low) inflamed monocytes, but not dendritic cells, into the kidney. These monocytes produced TNF-alpha, IL-6, IL-1alpha and IL-12. Ischemic injury induced in CCR2(-/-) mice or in CCR2(+/+) mice, made chimeric with CCR2(-/-) bone marrow, resulted in lower plasma creatinine levels and their kidneys had fewer infiltrated F4/80(low) macrophages compared to control mice. CX3CR1 expression contributed to monocyte recruitment into inflamed kidneys, as ischemic injury in CX3CR1(-/-) mice was reduced, with fewer F4/80(low) macrophages than controls. Monocytes transferred from CCR2(+/+) or CX3CR1(+/-) mice migrated into reperfused kidneys better than monocytes from either CCR2(-/-) or CX3CR1(-/-) mice. Adoptive transfer of monocytes from CCR2(+/+) mice, but not CCR2(-/-) mice, reversed the protective effect in CCR2(-/-) mice following ischemia-reperfusion. Egress of CD11b(+)Ly6C(high) monocytes from blood into inflamed kidneys was CCR2- and CX3CR1-dependent. Our study shows that inflamed monocyte migration, through CCR2- and CX3CR1-dependent mechanisms, plays a critical role in kidney injury following ischemia reperfusion.
Monocyte-to-High-Density Lipoprotein Cholesterol Ratio Is Independently Associated With All-Cause Mortality in Deceased Donor Kidney Transplant Recipients.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation
OBJECTIVES:The primary objective of this study was to evaluate the impact of monocyte-to-high-density lipoprotein cholesterol ratio on all-cause mortality in deceased donor kidney transplant recipients. MATERIALS AND METHODS:This was a retrospective observational study in which all deceased donor kidney transplant recipients were included. Relevant data for analyses included clinical and demographic features, laboratory values, number of HLA matches, occurrence of delayed graft function, cold ischemia time, and survival status. Kaplan-Meier survival analysis and Cox proportional hazards analysis were performed to determine the effects of monocyte-to-high-density lipoprotein cholesterol ratio on all-cause mortality. RESULTS:Our study included 325 deceased donor kidney transplant recipients (43.1% females, mean age of 44.5 ± 11.2 years). Median value of monocyte-to-high-density lipoprotein cholesterol ratio was 14.0 (interquartile range, 9.94-21.03). The total median observation time was 227 weeks (range, 115-345 weeks). Twenty deaths (12.3%) occurred during the follow-up period in recipients with monocyte-to-highdensity lipoprotein cholesterol ratio below median value, whereas 47 deaths (29%) occurred in recipients with ratio above the median (P < .001). Log-rank test showed significantly higher mortality in the group with monocyte-to high density lipoprotein cholesterol ratio higher than median (P = .001). In the multivariate Cox model, delayed graft function, duration of dialysis, cold ischemia time, and monocyte-to-high-density lipoprotein cholesterol ratio group appeared as independent predictors of all-cause mortality. CONCLUSIONS:Monocyte-to-high-density lipoprotein cholesterol ratio before kidney transplant seems to affect survival independently in deceased donor kidney transplant recipients.
Nature versus Number: Monocytes in Cardiovascular Disease.
Williams Helen,Mack Corinne D,Li Stephen C H,Fletcher John P,Medbury Heather J
International journal of molecular sciences
Monocytes play a key role in cardiovascular disease (CVD) as their influx into the vessel wall is necessary for the development of an atherosclerotic plaque. Monocytes are, however, heterogeneous differentiating from classical monocytes through the intermediate subset to the nonclassical subset. While it is recognized that the percentage of intermediate and nonclassical monocytes are higher in individuals with CVD, accompanying changes in inflammatory markers suggest a functional impact on disease development that goes beyond the increased proportion of these 'inflammatory' monocyte subsets. Furthermore, emerging evidence indicates that changes in monocyte proportion and function arise in dyslipidemia, with lipid lowering medication having some effect on reversing these changes. This review explores the nature and number of monocyte subsets in CVD addressing what they are, when they arise, the effect of lipid lowering treatment, and the possible implications for plaque development. Understanding these associations will deepen our understanding of the clinical significance of monocytes in CVD.
Long-Term Impact of Infection on Human Monocytes.
Ehmen Hauke G,Lüder Carsten G K
Frontiers in cellular and infection microbiology
is a prevalent parasite of mammals and birds including up to 30% of humans world-wide. Primary infection of immunocompetent hosts leads to a robust cell-mediated immune response, which controls but does not clear the infection, thus enabling long-term parasite persistence in brain and muscle tissues. Chronic toxoplasmosis in mice is associated with resistance to heterologous pathogens and this has been related to increased numbers of inflammatory monocytes. Here we have analyzed whether chronic infection impacts the subset distribution and the phenotype of peripheral human monocytes and their responses to parasite infection . CD14 monocytes from -seropositive blood donors expressed significantly less FcγRIII (CD16) than those from seronegative controls, but they did not show a shift in the distribution of classical, intermediate and non-classical monocyte subpopulations. Percentages of CD62L and CD64 monocytes were however decreased and increased, respectively, in chronically infected individuals as compared to naïve controls. Infection of monocyte-enriched PBMCs from both seropositive and seronegative individuals with led to an increase of CD14CD16 classical monocytes and a decrease of CD14CD16 double positive monocytes. Remarkably, after parasite infection, expression of the chemokine receptor CCR2 was severely impaired in monocytes from both, individuals with chronic toxoplasmosis and seronegative controls. In contrast, only monocytes from chronically infected humans but not those from controls dose-dependently up-regulated HLA-DR, DP, DQ expression following infection. Furthermore, monocyte-enriched PBMCs from seropositive individuals up-regulated IL-12 mRNA more vigorously after infection than cells from naïve controls. Collectively, our results establish that infection of humans with exerts long-term effects on the phenotype and responsiveness of blood monocytes. This may have important implications for innate immune responses to and unrelated pathogens.
CRIP1 expression in monocytes related to hypertension.
Schweigert Olga,Adler Julia,Längst Natalie,Aïssi Dylan,Duque Escobar Jorge,Tong Teng,Müller Christian,Trégouët David-Alexandre,Lukowski Robert,Zeller Tanja
Clinical science (London, England : 1979)
Hypertension is a complex and multifactorial disorder caused by lifestyle and environmental factors, inflammation and disease-related genetic factors and is a risk factor for stroke, ischemic heart disease and renal failure. Although circulating monocytes and tissue macrophages contribute to the pathogenesis of hypertension, the underlying mechanisms are poorly understood. Cysteine rich protein 1 (CRIP1) is highly expressed in immune cells, and CRIP1 mRNA expression in monocytes associates with blood pressure (BP) and is up-regulated by proinflammatory modulation suggesting a link between CRIP1 and BP regulation through the immune system. To address this functional link, we studied CRIP1 expression in immune cells in relation to BP using a human cohort study and hypertensive mouse models. CRIP1 expression in splenic monocytes/macrophages and in circulating monocytes was significantly affected by angiotensin II (Ang II) in a BP-elevating dose (2 mg/kg/day). In the human cohort study, monocytic CRIP1 expression levels were associated with elevated BP, whereas upon differentiation of monocytes to macrophages this association along with the CRIP1 expression level was diminished. In conclusion, CRIP1-positive circulating and splenic monocytes seem to play an important role in hypertension related inflammatory processes through endogenous hormones such as Ang II. These findings suggest that CRIP1 may affect the interaction between the immune system, in particular monocytes, and the pathogenesis of hypertension.
Monocytes and macrophages in ANCA-associated vasculitis.
Vegting Yosta,Vogt Liffert,Anders Hans-Joachim,de Winther Menno P J,Bemelman Frederike J,Hilhorst Marc L
Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are characterized by inflammation of small-to-medium-sized blood vessels and the presence of autoantibodies against cytoplasmic proteases sited in neutrophils and monocytes. Increasing evidence indicates a substantial role of monocytes and macrophages in the pathogenesis of AAV. Activated monocytes and macrophages contribute to necroinflammation in peripheral vasculitic lesions as well as to central and peripheral mechanisms of autoimmunity. The intermediate monocyte subset (CD14CD16) is increased and monocytes show elevated expression of CD14, Toll-like receptor 2/4, MHCII and integrins, likely reflecting activation and increased monocyte extravasation. Monocytes differentiate locally predominantly into alternatively activated (M2) macrophages, which are known for cell-clearance and phagocytosis, but may ultimately lead to fibrosis. Phagocytotic function of macrophages can be impaired by surface expression of cytoplasmic proteases on apoptotic neutrophils and causes release of inflammatory cytokines and immunogenic contents, presumably resulting in a vicious circle of increased neutrophil, T and B cell activation and consequent ANCA production. Considering their crucial role in initiating necroinflammation as well as fibrogenesis, monocytes and macrophages may represent a logic first-line target for new treatment options in AAV.
Monocytes in myocardial infarction.
Dutta Partha,Nahrendorf Matthias
Arteriosclerosis, thrombosis, and vascular biology
Myocardial infarction (MI) is the leading cause of death in developed countries. Though timely revascularization of the ischemic myocardium and current standard therapy reduce acute mortality after MI, long-term morbidity and mortality remain high. During the first 1 to 2 weeks after MI, tissues in the infarcted myocardium undergo rapid turnover, including digestion of extracellular matrix and fibrosis. Post-MI repair is crucial to survival. Monocytes recruited to the infarcted myocardium remove debris and facilitate the repair process. However, exaggerated inflammation may also impede healing, as demonstrated by the association between elevated white blood cell count and in-hospital mortality after MI. Monocytes produced in the bone marrow and spleen enter the blood after MI and are recruited to the injured myocardium in 2 phases. The first phase is dominated by Ly-6c(high) monocytes and the second phase by Ly-6c(low) monocytes. Yet the number of Ly6C(low) monocytes recruited to the infarct is much lower, and Ly6C(high) monocytes can differentiate to Ly6C(low) macrophages in later healing stages. Understanding the signals regulating monocytosis after MI will help design new therapies to facilitate cardiac healing and limit heart failure.
New prognostic factor for hepatitis B virus-related decompensated cirrhosis: Ratio of monocytes to HDL-cholesterol.
Wu Qianxia,Mao Weilin
Journal of clinical laboratory analysis
AIM:Hepatitis B virus-related decompensated cirrhosis (HBV-DeCi) has a high mortality rate, and it remains a challenge to predict its outcomes in clinical practice. We aimed to determine the association between monocyte-to-HDL-cholesterol ratio (MHR) and short-term prognosis in HBV-DeCi patients. METHODS:A total of 145 HBV-DeCi patients were enrolled. A multivariate analysis was performed to identify predictors of mortality. The findings were validated by a receiver operating characteristic analysis using the area under the curve (AUC). RESULTS:A total of 20 (13.8%) patients had died 30 days after admission. MHR was markedly increased in the non-survivors compared with the survivors. In the multivariate analysis, MHR was identified as an independent risk factor for mortality, with a significant predictive value (AUC = 0.825; sensitivity, 90.0%; specificity, 62.4%). CONCLUSIONS:Elevated MHR is associated with increased mortality rate in HBV-DeCi patients.
Low-density granulocytes and monocytes as biomarkers of cardiovascular risk in systemic lupus erythematosus.
López Patricia,Rodríguez-Carrio Javier,Martínez-Zapico Aleida,Pérez-Álvarez Ángel I,Suárez-Díaz Silvia,Mozo Lourdes,Benavente Lorena,Caminal-Montero Luis,Suárez Ana
Rheumatology (Oxford, England)
OBJECTIVE:The aim was to evaluate the most relevant cell populations involved in vascular homeostasis as potential biomarkers of SLE-related cardiovascular disease (CVD). METHODS:Low-density granulocytes (LDGs), monocyte subsets, endothelial progenitor cells, angiogenic T (Tang) cells, CD4+CD28null and Th1/Th17 lymphocytes and serum cytokine levels were quantified in 109 SLE patients and 33 controls in relationship to the presence of subclinical carotid atheromatosis or cardiovascular disease. A second cohort including 31 recent-onset SLE patients was also included. RESULTS:Raised monocyte and LDG counts, particularly those LDGs negative for CD16/CD14 expression (nLDGs), in addition to the ratios of monocytes and nLDGs to high-density lipoprotein-cholesterol (HDLc) molecules (MHR and nLHR, respectively), were present in SLE patients with traditional risk factors or subclinical atheromatosis but not in those who were CV-free, thus revealing their value in the identification of patients at risk of CVD, even at the onset of disease. Accordingly, nLDGs were correlated positively with carotid intima-media thickness (cIMT) and with inflammatory markers (CRP and IL-6). A bias towards more differentiated monocyte subsets, related to increased IFN-α and IL-17 serum levels, was also observed in patients. Intermediate monocytes were especially expanded, but independently of their involvement in CVD. Finally, CD4+CD28null, Th17 and Th1 lymphocytes were increased, with CD4+CD28null and Th17 cells being associated with cIMT, whereas endothelial progenitor and Tang cell levels were reduced in all SLE patients. CONCLUSION:The present study highlights the potential use of MHR and nLHR as valuable biomarkers of CVD risk in SLE patients, even at diagnosis. The increased amounts of nLDGs, monocytes, Th17 and senescent-CD28null subsets, coupled with reduced pro-angiogenic endothelial progenitor cells and Tang cells, could underlie the development of atheromatosis in SLE.
Neutrophil to Lymphocyte Ratio (NLR) is a Better Tool Rather than Monocyte to High-Density Lipoprotein Ratio (MHR) and Platelet to Lymphocyte Ratio (PLR) in Central Retinal Artery Occlusions.
Guven Soner,Kilic Deniz
Ocular immunology and inflammation
: To evaluate the predictive value of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to high-density lipoprotein (HDL) ratio (MHR) and blood lipid profile in central retinal artery occlusion (CRAO) patients.: We included 37 patients with a diagnosis of CRAO and 36 healthy subjects with similar age-sex in the study. We analyzed the medical records of peripheral blood samples retrospectively. NLR, PLR, MHR were obtained by simple manually calculations.: CRAO patients had significantly higher mean NLR in comparison with healthy subjects (p: 0.009). The groups were similar in regard to mean PLR (p: 0.864) and mean MHR (p: 0.581). A cutoff value of >1.62 for NLR was found to be a diagnostic tool in CRAO. The sensitivity and specificity for this cutoff point was 83.8% and 55.6%, respectively.: NLR rather than MHR and PLR may be a beneficial marker for the development of CRAO.
Acute exercise-induced response of monocyte subtypes in chronic heart and renal failure.
Van Craenenbroeck Amaryllis H,Van Ackeren Katrijn,Hoymans Vicky Y,Roeykens Johan,Verpooten Gert A,Vrints Christiaan J,Couttenye Marie M,Van Craenenbroeck Emeline M
Mediators of inflammation
PURPOSE:Monocytes (Mon1-2-3) play a substantial role in low-grade inflammation associated with high cardiovascular morbidity and mortality of patients with chronic kidney disease (CKD) and chronic heart failure (CHF). The effect of an acute exercise bout on monocyte subsets in the setting of systemic inflammation is currently unknown. This study aims (1) to evaluate baseline distribution of monocyte subsets in CHF and CKD versus healthy subjects (HS) and (2) to evaluate the effect of an acute exercise bout. Exercise-induced IL-6 and MCP-1 release are related to the Mon1-2-3 response. METHODS:Twenty CHF patients, 20 CKD patients, and 15 HS were included. Before and after a maximal cardiopulmonary exercise test, monocyte subsets were quantified by flow cytometry: CD14(++)CD16(-)CCR2(+) (Mon1), CD14(++)CD16(+)CCR2(+) (Mon2), and CD14(+)CD16(++)CCR2(-) (Mon3). Serum levels of IL-6 and MCP-1 were determined by ELISA. RESULTS:Baseline distribution of Mon1-2-3 was comparable between the 3 groups. Following acute exercise, %Mon2 and %Mon3 increased significantly at the expense of a decrease in %Mon1 in HS and in CKD. This response was significantly attenuated in CHF (P < 0.05). In HS only, MCP-1 levels increased following exercise; IL-6 levels were unchanged. Circulatory power was a strong and independent predictor of the changes in Mon1 (β = -0.461, P < 0.001) and Mon3 (β = 0.449, P < 0.001); and baseline LVEF of the change in Mon2 (β = 0.441, P < 0.001). CONCLUSION:The response of monocytes to acute exercise is characterized by an increase in proangiogenic and proinflammatory Mon2 and Mon3 at the expense of phagocytic Mon1. This exercise-induced monocyte subset response is mainly driven by hemodynamic changes and not by preexistent low-grade inflammation.
Monocyte Subsets and Inflammatory Cytokines in Acute Decompensated Heart Failure.
Goonewardena Sascha N,Stein Adam B,Tsuchida Ryan E,Rattan Rahul,Shah Dhavan,Hummel Scott L
Journal of cardiac failure
BACKGROUND:Distinct monocyte subsets predict cardiovascular risk and contribute to heart failure progression in murine models, but they have not been examined in clinical acute decompensated heart failure (ADHF). METHODS AND RESULTS:Blood samples were obtained from 11 healthy control subjects (HCs) and at admission and discharge from 19 ADHF patients. Serologic markers of inflammation were assessed at admission and discharge. Monocyte populations were defined with the use of flow cytometry for cell-surface expression of CD14 and CD16: CD14++CD16- (classic), CD14++CD16+ (intermediate), and CD14+CD16++ (nonclassic). In ADHF patients, C-reactive protein (CRP) and interleukin-6 (IL-6) were higher compared with HCs (both P < .001) and decreased from admission to discharge (CRP: 12.1 ± 10.1 to 8.6 ± 8.4 mg/L [P = .005]; IL-6: 19.8 ± 34.5 to 7.1 ± 4.7 pg/mL [P = .08]). In ADHF patients, the admission proportion of CD14++CD16- monocytes was lower (68% vs 85%; P < .001) and that of CD14++CD16+ (15% vs 8%; P = .002) and CD14+CD16++ (17% vs 7%, P = .07) monocytes higher compared with HCs. Additionally, the proportion of CD14++CD16- monocytes increased (68% to 79%, P = .04) and the CD14+CD16++ monocytes decreased (17% to 7%, P = .049) between admission and discharge. CONCLUSIONS:Following standard treatment of ADHF, the monocyte profile and circulating inflammatory markers shifts to more closely resemble those of HC, suggesting a resolution of the acute inflammatory state. Functional studies are warranted to understand how specific monocyte subsets and systemic inflammation may contribute to ADHF pathophysiology.
Impact of monocyte to high-density lipoprotein ratio on the identification of prevalent coronary heart disease: insights from a general population.
BACKGROUND:Recent studies have identified monocyte to high-density lipoprotein ratio (MHR) as a simple, practical surrogate of atherosclerosis. Considering atherosclerosis is a major mechanism of coronary heart disease (CHD). The present study aims to evaluate the association between MHR and the prevalence of CHD. METHODS AND RESULTS:The present cross-sectional work included 6442 participants (mean age: 59.57 years, 60.2% females), all of them were included from rural areas of northern China between October 2019 to April 2020. MHR was acquired as monocytes count divided by high-density lipoprotein concentration. Prevalent CHD researched 3.14%. After adjustment of sex, age, current drinking and smoking, BMI, WC, diabetes, hypertension, LDL-C, TG, eGFR, lipid-lowering therapy and cerebrovascular disease history, each standard deviation increase of MHR cast a 39.5% additional CHD risk. Furthermore, the top quartile of MHR had an additional 89.0% CHD risk than the bottom quartile. Besides, smooth curve fitting revealed a linear pattern of the association. Additionally, the stratified evaluation showed a robust correlation among the subgroups divided by CHD risk factors. Finally, area under the curve demonstrated an advancement when including MHR into common CHD risk factors (0.744 vs 0.761, p < 0.001). Consistently, reclassification analysis indicated the improvement from MHR (all P = 0.003). CONCLUSION:Our work suggests the robust and linear relationship between MHR and the prevalent CHD in a general population, providing epidemiological evidence for laboratory studies. More importantly, the findings implicate the efficacy of MHR to be a potential indicator to identify the prevalent CHD.
Compared with the monocyte to high-density lipoprotein ratio (MHR) and the neutrophil to lymphocyte ratio (NLR), the neutrophil to high-density lipoprotein ratio (NHR) is more valuable for assessing the inflammatory process in Parkinson's disease.
Liu Zhu,Fan Qingli,Wu Shizheng,Wan Yaqi,Lei Yancheng
Lipids in health and disease
BACKGROUND:The inflammatory response plays essential roles in the pathological process and prognosis of Parkinson's disease (PD). This research investigated the predictive value of the neutrophil to high-density lipoprotein ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to high-density lipoprotein ratio (MHR) for PD. METHODS:Patients with PD (n = 98) were divided into three groups according to disease duration: < 6 years (n = 55), 6-10 years (n = 29) and > 10 years (n = 14). Based on the classification system of Hoehn and Yahr, grades 1 ~ 2.5 were considered early-stage PD (n = 44), and grades 3 ~ 5 were considered advanced-stage PD (n = 54). In addition, healthy subjects (n = 98) matched to the above PD patients in the same period were selected as the control group. Differences in the NHR, NLR, MHR and other indicators among the groups were evaluated. RESULTS:Smoking, drinking, the neutrophil count and the NHR and NLR were remarkably greater and hypertension, index of body mass, the lymphocyte count, and the levels of cholesterol in total, triglycerides, lipoprotein cholesterol with low density and uric acid were sharply lower in the PD group compared with in the control group. Analysis of multifactor logistic regression indicated that the NHR (odds ratio (adjusted OR) = 1.576, 95% CI: 1.053 ~ 2.358, P = 0.027) and NLR (adjusted OR = 1.734, 95% CI: 1.046 ~ 2.876, P = 0.033) were factors of risk for PD, while the MHR was not significantly correlated with PD. The areas under the receiver operating characteristic (ROC) curve (AUCs) for the prediction of PD by the NHR and NLR were 0.654 (95% CI: 0.583 ~ 0.721, P = 0.0001) and 0.69 (95% CI: 0.62 ~ 0.754, P < 0.0001), respectively, and the optimal cutoff values were 1.848 × 10/mmol and 2.62 × 10/mmol. Spearman's correlation analysis indicated that the NHR was correlated with the disease duration significantly negatively and that the MHR was positively correlated with disease severity. CONCLUSIONS:In summary, the NHR not only has strong predictive value for PD but is also closely related to disease duration. The NHR may be a better prediction for the long-period clinical results in PD patients than the MHR and NLR. TRIAL REGISTRATION:Clinical medical reserach center project of Qinghai Province (2017-SF-L1).
Correlation of monocyte/HDL ratio (MHR) with inflammatory parameters in obese patients diagnosed with polycystic ovary syndrome.
Herkiloglu Dilsad,Gokce Sefik
OBJECTIVES:Monocyte/high density lipprotein (HDL) ratio (MHR) has been reported to be associated with obesity and polycystic ovarian syndrome (PCOS). In this study, it was aimed to evaluate whether there is a relationship between PCOS and MHR and inflammatory parameters, to investigate the relationship level of MHR and lymphocyte/monocyte ratio (LMR), which are easily accessible inflammatory and oxidative stress markers, with obese women with PCOS, and to determine the usability of MHR as a predictive marker for PCOS. MATERIAL AND METHODS:The study included 64 PCOS-patients who were admitted to Gynecology clinics and 52 healthy women. RESULTS:The mean MHR (12.5 ± 4.6) in the PCOS group was significantly higher than the control group (10.4 ± 4.0) (p = 0.01). In the examination performed by combining the groups PCOS and obesity status, the mean MHR value in the PCOS-obese group was significantly higher than all the other groups (p = 0.004). In the ROC analysis, the threshold value of 10.1 for MHR was found to have a sensitivity of 84.8% and specificity of 58.5% in determining the association between PCOS and obesity (AUC: 0.721; p < 0.001; LB: 0.628; UB: 0.814; CI 95%). Accordingly, the rate of those with MHR level of 10.1 and above was significantly higher in the PCOS group compared to the control group (67.2% vs 40.4%) (p = 0.001). In the logistic regression analysis, the determination is increased by 3,026 times (odds ratio; 1.401-6.535) in predicting the presence of PCOS in those with MHR value of 10.1 and above, and 7,576 times (Odds ratio; 2.652-21.646) in predicting the presence of PCOS + obesity was found to be. Correlation analysis in PCOS patients revealed that the MHR value was negatively correlated with age (p = 0.001; r = -0.412), LMR (p = 0.003; r = -0.377), and total cholesterol [p = 0.018; correlation coefficient (r) = -0.302]. CONCLUSIONS:This study findings showed that MHR level is significantly related to PCOS, and especially MHR values above 10.1 may be a significant predictive marker for PCOS. Our study findings also show that an association of PCOS and obesity is a very important trigger on MHR.
Monocyte to High-Density Lipoprotein Ratio (MHR) as a predictor of mortality and Major Adverse Cardiovascular Events (MACE) among ST Elevation Myocardial Infarction (STEMI) patients undergoing primary percutaneous coronary intervention: a meta-analysis.
Villanueva Danielle Louis E,Tiongson Marc Denver,Ramos John Daniel,Llanes Elmer Jasper
Lipids in health and disease
BACKGROUND:Monocyte to High Density Lipoprotein Ratio (MHR) is a new marker that has been associated with major adverse cardiovascular outcomes among STEMI patients. We sought to strengthen the association between MHR and mortality and major adverse cardiovascular events (MACEs) among STEMI patients who underwent primary percutaneous coronary intervention. METHODS:Studies were included if they satisfied the following criteria:1) Observational Studies; 2) Adult patients with ST-elevation Myocardial Infarction (STEMI) who underwent primary percutaneous intervention (PCI); and 3) Reported data on mortality and major adverse cardiovascular events. Using MEDLINE, Clinical Key, Science Direct, Scopus, and Cochrane Central Register of Controlled Trials databases, a search for eligible studies was conducted until September 2017. Our primary outcome of interest was all-cause cardiovascular (CV) mortality. We also investigated the association between MHR and major adverse cardiovascular events (MACEs). RESULTS:We identified 3 studies involving 2793 STEMI patients, showing that in STEMI patients who underwent primary PCI, a high admission MHR is associated with a significantly higher in-hospital mortality [RR 4.71, (95% CI 2.36 to 9.39, p < 0.00001] and in-hospital MACE [RR 1.90, (95% CI 1.44 to 2.50), p < 0.00001]. This significant association was not observed in long term mortality or MACE. CONCLUSION:A high admission MHR among STEMI patients who underwent primary PCI is associated with a higher in-hospital mortality and MACE. This novel marker can be used as an inexpensive and readily available tool for risk stratification.
Investigating the relationship between the severity of coronary artery disease and inflammatory factors of MHR, PHR, NHR, and IL-25.
Manoochehri Hamed,Gheitasi Reza,Pourjafar Mona,Amini Razieh,Yazdi Amirhossein
Medical journal of the Islamic Republic of Iran
Coronary artery disease (CAD), as a most common cause of death, is mainly caused by atherosclerosis. Due to the role of inflammation in the process of atherosclerosis, in the present study, the relationship between the severity of coronary artery disease and inflammatory factors of monocyte to HDL-C ratio (MHR), platelet-to-HDL-C ratio (PHR), neutrophil to HDL-C ratio (NHR), and IL-25 was investigated. In this cross-sectional study, 64 patients with diagnosis of coronary artery disease who were undergoing angiography in Farshchian heart center in Hamadan were studied. For each patient, the count of monocytes, neutrophils, platelet, and HDL-C, and IL-25 were measured from their blood and serum samples. Also, demographic information, such as age, gender, diabetes, smoking, and history of hypertension, was collected using a checklist. Data were described using frequency, percent, mean, and standard deviation. Statistical analysis was performed using independent t test, Mann-Whitney, Wilcoxon, and Spearman rank correlation tests, and multiple linear regression by SPSS version 25.0 SPSS Inc). P <.05 was considered as significant. The results of this study showed that IL-25 and MHR index has a significant correlation with coronary artery disease and Gensini score (P ˂.001). The PHR index was associated with coronary artery disease. Also, qualitative variables, such as history of hypertension, history of smoking, and gender, have a significant association with the severity of coronary artery disease (P <.05). Among the inflammatory markers examined, IL-25 and MHR are stronger markers for assessing the severity of coronary artery disease. Simple and available IL-25 and MHR measurements may be able to, along with common risk factors and lipid profiles, predict the amount of vascular occlusion in treatment centers as an alternative of angiography as well as screening high risk patients prone to cardiovascular disease.
May Monocyte/HDL Cholesterol Ratio (MHR) and Neutrophil/Lymphocyte Ratio (NLR) Be an Indicator of Inflammation and Oxidative Stress in Patients with Keratoconus?
Katipoğlu Zeynep,Mirza Enver,Oltulu Refik,Katipoglu Bilal
Ocular immunology and inflammation
OBJECTIVE:To evaluate monocyte/high-density lipoprotein cholesterol ratio (MHR) and neutrophil/lymphocyte ratio (NLR) in patients with keratoconus (KC). METHODS:Thirty-one patients with KC (group 1) and 31 healthy control subjects (group 2) were included in the study. All participants' ocular examination findings, clinical and laboratory parameters were obtained from file records and laboratory archives. RESULTS:When group 1 was compared with group 2, MHR (13.7 ± 5.0 vs. 9.1 ± 3.7; < .001) and NLR (2.3 ± 0.8 vs. 1.7 ± 0.6; < .001) were statistically significantly higher in group 1. Optimal MHR cutoff value for KC was calculated as 10.2 with 77.4% sensitivity and 64.5% specificity, and optimal NLR cut-off value for KC was found as 1.9 with 71.4% sensitivity and 55% specificity. CONCLUSION:MHR and NLR values recognized as indicators of oxidative stress and systemic inflammation were significantly higher in patients with KC compared to the control group.
[Association of RAGE gene polymorphisms with MHR ratio and heart rate variability among patients with coronary heart disease].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics
OBJECTIVE:To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD). METHODS:120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed. RESULTS:The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency. CONCLUSION:Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.
Gender, BMI and fasting hyperglycaemia influence Monocyte to-HDL ratio (MHR) index in metabolic subjects.
Battaglia Stefano,Scialpi Natasha,Berardi Elsa,Antonica Gianfranco,Suppressa Patrizia,Diella Francesco Arcangelo,Colapietro Francesca,Ruggieri Roberta,Guglielmini Giuseppe,Noia Alessia,Graziano Giusi,Sabbà Carlo,Cariello Marica
Metabolic Syndrome (MS) is characterized by a low-grade inflammatory state causing an alteration of non-invasive indexes derived from blood count, namely monocyte-to-HDL ratio (MHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). We analyse a population of 771 subjects (394 controls and 377 MS patients) to evaluate the best predictive index of MS. The diagnosis of MS was made according to the 2006 criteria of the International Diabetes Federation (IDF). We performed ROC curve analyses to evaluate the best predictor index of MS. MHR cut-off value was used to classify the population in two different groups and to create the outcome variable of the Recursive Partitioning and Amalgamation (RECPAM) analysis. This method is a tree-structured approach that defines "risk profiles" for each group of dichotomous variables. We showed that MHR index is significantly linked to body mass index (BMI), waist circumference, creatinine, C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR). ROC curve defined an MHR cut-off value of 6.4, which was able to identify two patient groups with significant differences in waist circumference, blood pressure, creatinine, estimated glomerular filtration rate and fasting plasma glucose. RECPAM analysis demonstrated that gender, BMI categorization and hyperglycaemia were the most important risk determinants of increased MHR index that can be considered bona fide a useful and easily obtainable tool to suggest the presence of peculiar metabolic features that predict MS.
Correlation between GPR, MHR and elderly essential hypertension with unstable angina pectoris.
Liu Xiaoteng,Zhang Ying,Jin Fengbiao,Liu Huiqing,Li Qinglian,Gao Yu,Hou Ruitian,Zhang Zhimin
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
OBJECTIVES:To investigate the level and significance of serum γ-glutamyl transferase-to-platelet ratio (GPR) and monocyte count to high-density lipoprotein ratio (MHR) in patients with essential hypertension (EH) and unstable angina (UA). METHODS:A total of 218 patients with coronary angiography aged ≥60 years, who were admitted to the EH hospital of the Department of Cardiac Medicine, Affiliated Hospital of Chengde Medical College, were selected from September 2018 to September 2019. They were divided into an EH+UA group (=113) and an EH group (=105). In addition, 106 patients with normal coronary angiography who were diagnosed with coronary heart disease were selected as a control group. The general data, blood biochemical indicators, GPR and MHR in each group were compared, and partial correlation analysis and receiver operator characteristic (ROC) curve analysis were performed. RESULTS:Compared with the control group, patients in the EH+UA group and the EH group had higher body mass index (BMI), tyiglyceride (TG), GPR, and MHR, and lower high-density lipoprotein-cholesterol (HDL-C) (all <0.05); and patients in the EH+UA group had higher white blood cell counts, alanine aminotransferase (ALT), and uric acid (all <0.05). Compared with the EH group, patients in the EH+UA group had higher GPR and MHR (both <0.05). Partial correlation analysis showed that after controlling the antihypertensive drugs and lipid-lowering drugs, GPR was found to be positively correlated with BMI, white blood cell count, ALT, TG, and uric acid (=0.160, 0.111, 0.205, 0.250, 0.154, respectively, all <0.05), which was negatively correlated with HDL-C (=-0.238, <0.05); MHR was positively correlated with BMI, ALT, TG, uric acid, and GPR (=0.186, 0.307, 0.157, 0.141, 0.223, respectively, all <0.05), and negatively correlated with HDL-C (=-0.610, <0.001). ROC curve analysis showed that GPR had higher specificity and positive predictive value, while MHR had higher sensitivity. When the two indicators were combined, the sensitivity and positive predictive value were higher. CONCLUSIONS:There is a correlation between GPR, MHR and EH combined with UA pectoris, and the combined detection of the two indicators has adjuvant diagnostic value for elderly EH combined with UA.
The role of plasma triglyceride/high-density lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease.
Sonmez Alper,Yilmaz Mahmut Ilker,Saglam Mutlu,Unal Hilmi Umut,Gok Mahmut,Cetinkaya Hakki,Karaman Murat,Haymana Cem,Eyileten Tayfun,Oguz Yusuf,Vural Abdulgaffar,Rizzo Manfredi,Toth Peter P
Lipids in health and disease
BACKGROUND:Cardiovascular disease (CVD) risk is substantially increased in subjects with chronic kidney disease (CKD). The Triglycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C) ratio is an indirect measure of insulin resistance and an independent predictor of cardiovascular risk. No study to date has been performed to evaluate whether the TG/HDL-C ratio predicts CVD risk in patients with CKD. METHODS:A total of 197 patients (age 53±12 years) with CKD Stages 1 to 5, were enrolled in this longitudinal, observational, retrospective study. TG/HDL-C ratio, HOMA-IR indexes, serum asymmetric dimethyl arginine (ADMA), high sensitivity C-reactive protein (CRP), parathyroid hormone (PTH), calcium, phosphorous, estimated glomerular filtration rate (eGFR), and albumin levels were measured. Flow mediated vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasonography. RESULTS:A total of 11 cardiovascular (CV) deaths and 43 nonfatal CV events were registered in a mean follow-up period of 30 (range 9 to 35) months. Subjects with TG/HDL-C ratios above the median values (>3.29) had significantly higher plasma ADMA, PTH, and phosphorous levels (p=0.04, p=0.02, p=0.01 respectively) and lower eGFR and FMD values (p=0.03, p<0.001 respectively). The TG/HDL-C ratio was an independent determinant of FMD (β=-0.25 p=0.02) along with TG, HDL-C, hsCRP, serum albumin, phosphate levels, systolic blood pressure, PTH, eGFR and the presence of diabetes mellitus. The TG/HDL-C ratio was also a significant independent determinant of cardiovascular outcomes [HR: 1.36 (1.11-1.67) (p=0.003)] along with plasma ADMA levels [HR: 1.31 (1.13-1.52) (p<0.001)] and a history of diabetes mellitus [HR: 4.82 (2.80-8.37) (p<0.001)]. CONCLUSION:This study demonstrates that the elevated TG/HDL-C ratio predicts poor CVD outcome in subjects with CKD. Being a simple, inexpensive, and reproducible marker of CVD risk, the TG/HDL-C ratio may emerge as a novel and reliable indicator among the many well-established markers of CVD risk in CKD. SYSTEMATIC REVIEW REGISTRATION:Clinical trial registration number and date: NCT02113462 / 10-04-2014.
High-density lipoprotein cholesterol and arterial calcification in midlife women: the contribution of estradiol and C-reactive protein.
Swabe Gretchen,Matthews Karen,Brooks Maria,Janssen Imke,Wang Norman,El Khoudary Samar R
Menopause (New York, N.Y.)
OBJECTIVE:Studies suggest a reversal in the protective association of high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease in women traversing menopause. Decreasing estrogen levels during the transition, as well as inflammation, may explain this reversal. We tested whether either estradiol or C-reactive protein (CRP) concentrations modified the association of HDL-C with aortic (AC) or coronary artery calcification (CAC). METHODS:A total of 478 participants between ages 46 to 59 from the Study of Women's Health Across the Nation Heart baseline visit were included. AC and CAC presence were defined as Agatston score of 100 or higher and 10 or higher, respectively. Logistic regression was used for analysis. RESULTS:A total of 112 (23.53%) participants had AC 100 or higher and 104 (21.76%) had CAC 10 or higher. In unadjusted models, a 1-mg/dL higher in HDL-C was associated with 3% lower odds of AC (95% CI: 0.95-0.99) and 4% lower odds of CAC (95% CI: 0.95-0.98). In adjusted models, a significant interaction between HDL-C and estradiol with respect to AC but not CAC was detected, such that higher HDL-C level was protective at the highest estradiol quartile (odds ratio: 0.91, 95% CI: 0.84-0.99 per 1 mg/dL higher HDL-C, P = 0.03) but tended to associate with greater risk at the lowest quartile (odds ratio: 1.04, 95% CI: 0.98-1.10 per 1 mg/dL higher HDL-C, P = 0.16). CRP did not modify any association. CONCLUSIONS:The protective cardiovascular association of higher HDL-C levels on AC was modified by estradiol but not CRP concentrations. The pathways through which estradiol might influence this association should be further investigated.
Association between high-density lipoprotein subfractions and low-grade inflammation, insulin resistance, and metabolic syndrome components: The ELSA-Brasil study.
Generoso Giuliano,Bensenor Isabela M,Santos Raul D,Santos Itamar S,Goulart Alessandra C,Jones Steven R,Kulkarni Krishnaji R,Blaha Michael J,Toth Peter P,Lotufo Paulo A,Bittencourt Marcio Sommer
Journal of clinical lipidology
BACKGROUND:High-density lipoprotein cholesterol (HDL-C) can be divided into subfractions, which may have variable effects in atherogenesis. The results about the association between HDL-C subfractions and risk factors for cardiovascular disease are mixed. OBJECTIVE:The objective of this study was to analyze the association between HDL-C subfractions and each metabolic syndrome component, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and C-reactive protein (CRP). METHODS:Four thousand five hundred thirty-two individuals between 35 and 74 years old without previous manifest cardiovascular disease not using fibrates were enrolled. HDL-C subfractions were separated by vertical ultracentrifugation (vertical auto profile-in mg/dL) into HDL-C and HDL-C. HDL-C/HDL-C ratio, HOMA-IR, and high-sensitivity CRP were also included in the analysis. RESULTS:Mean age of participants was 51 ± 9 years, and 54.8% were women. In univariate analysis, HDL-C, HDL-C, and HDL-C were all inversely associated with each of the metabolic syndrome defining factors, HOMA-IR values, and serum CRP. We also observed a negative association between HDL-C/HDL-C ratio with the variables aforementioned even after adjusting for smoking, alcohol use, physical activity, and HDL-C levels (P < .01). CONCLUSION:HDL-C and its subfractions (HDL-C and HDL-C) are inversely associated with the defining features of metabolic syndrome, insulin resistance, and systemic inflammation. In addition, the HDL-C/HDL-C ratio measured by vertical auto profile is significantly associated with the former factors even after comprehensive adjustment for HDL-C and other confounding variables.
Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment.
Ansell Benjamin J,Navab Mohamad,Hama Susan,Kamranpour Naeimeh,Fonarow Gregg,Hough Greg,Rahmani Shirin,Mottahedeh Rachel,Dave Ravi,Reddy Srinivasa T,Fogelman Alan M
BACKGROUND:The inflammatory/antiinflammatory properties of HDL were compared with HDL cholesterol in 2 groups of patients and in age- and sex-matched control subjects. METHODS AND RESULTS:Group 1 consisted of 26 patients not yet taking a statin who presented with coronary heart disease (CHD) or CHD equivalents by National Cholesterol Education Program Adult Treatment Panel III criteria studied before and 6 weeks after 40 mg/d of simvastatin. Group 2 consisted of 20 patients with documented CHD and HDL cholesterol > or =84 mg/dL. The inflammatory/antiinflammatory properties of HDL were determined by the ability of the subject's HDL to alter LDL-induced monocyte chemotactic activity (MCA) in a human artery wall coculture. Induction of MCA by a control LDL was determined in the absence or presence of the subject's HDL. Values in the absence of HDL were normalized to 1.0. Values >1.0 after the addition of HDL indicated proinflammatory HDL; values <1.0 indicated antiinflammatory HDL. Group 1 values before simvastatin were LDL cholesterol, 118+/-24 mg/dL; HDL cholesterol, 57+/-13 mg/dL; triglycerides, 125+/-64 mg/dL; and high-sensitivity C-reactive protein (hs-CRP), 1.7+/-1.9 mg/L; and MCA values were 1.38+/-0.91, compared with 0.38+/-0.14 for control subjects (P=1.5x10(-5)). After simvastatin, values were LDL cholesterol, 73+/-24 mg/dL; HDL cholesterol, 61+/-14 mg/dL; triglycerides, 99+/-52 mg/dL; and hs-CRP, 1.3+/-1.3 mg/L; and MCA values were 1.08+/-0.71. In group 2, values were LDL cholesterol, 108+/-34 mg/dL; HDL cholesterol, 95+/-14 mg/dL; triglycerides, 89+/-44 mg/dL; and hs-CRP, 0.8+/-0.7 mg/L; and MCA values were 1.28+/-0.29, compared with 0.35+/-0.11 for control subjects (P=1.7x10(-14)). Similar results were obtained with the cell-free assay. CONCLUSIONS:The inflammatory/antiinflammatory properties of HDL distinguished patients from control subjects better than HDL cholesterol and were improved with simvastatin.
The association between reduction in inflammation and changes in lipoprotein levels and HDL cholesterol efflux capacity in rheumatoid arthritis.
Liao Katherine P,Playford Martin P,Frits Michelle,Coblyn Jonathan S,Iannaccone Christine,Weinblatt Michael E,Shadick Nancy S,Mehta Nehal N
Journal of the American Heart Association
BACKGROUND:Potent anti-inflammatory rheumatoid arthritis (RA) treatments are associated with reduced cardiovascular risk as well as increases in low-density lipoprotein (LDL) cholesterol. This apparent paradox may be explained by favorable changes in other lipid measurements. The objective of this study was to determine the longitudinal association between changes in inflammation with advanced lipoprotein measurements and high-density lipoprotein (HDL) cholesterol efflux capacity. METHODS AND RESULTS:We conducted this study in a longitudinal RA cohort from a large academic center, including subjects with high-sensitivity C-reactive protein (hs-CRP) reduction ≥10 mg/L at 2 time points 1 year apart. Subjects receiving statins during the study period or preceding 6 months were excluded. We compared total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B, and apolipoprotein A1 levels and HDL cholesterol efflux capacity at baseline and 1-year follow-up by using the paired t test. We also assessed the correlations between reductions in hs-CRP with percentage change in lipid parameters. We studied 90 RA subjects (mean age 57 years, 89% female), all of whom were receiving disease-modifying antirheumatic drugs. We observed a 7.2% increase in LDL cholesterol levels (P=0.02) and improvement in efflux capacity by 5.7% (P=0.002) between baseline and follow-up, with a median hs-CRP reduction of 23.5 mg/L. We observed significant correlations between reductions in hs-CRP with increases in apolipoprotein A1 (r=0.27, P=0.01) and HDL cholesterol efflux capacity (r=0.24, P=0.02). CONCLUSION:Among RA subjects experiencing reductions in hs-CRP, we observed increased LDL cholesterol levels and concomitant improvements in HDL cholesterol efflux capacity. These findings provide further insight into lipid modulation and the beneficial effect of reduction in inflammation on lipids in vivo.
Inflammation Alters Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW-CKD.
Kim Jae Young,Park Jung Tak,Kim Hyung Woo,Chang Tae-Ik,Kang Ea Wha,Ahn Curie,Oh Kook-Hwan,Lee Joongyub,Chung Wookyung,Kim Yong-Soo,Kim Soo Wan,Yoo Tae-Hyun,Kang Shin-Wook,Han Seung Hyeok,
Journal of the American Heart Association
Background The function of high-density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high-density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high-density lipoprotein cholesterol (HDL-C) level. Presence of inflammation was defined by hs-CRP (high-sensitivity C-reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person-years of follow-up, overall incidence of the primary outcome was 15.8 per 1000 person-years. In multivariable Cox analysis after adjusting for confounders, HDL-C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL-C for risk of extended major adverse cardiovascular events (=0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL-C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50-1.82), 0.95 (0.50-1.82), and 0.42 (0.19-0.95), respectively, compared with HDL-C of 40 to 49 mg/dL. However, the significant association for HDL-C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL-C groups (HRs [95% CIs], 0.73 [0.37-1.43], 1.24 [0.59-2.61], and 1.56 [0.71-3.45], respectively), but without statistical significance. Conclusions The association between HDL-C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.
High density lipoprotein cholesterol / C reactive protein ratio in heart failure with preserved ejection fraction.
ESC heart failure
AIMS:The impacts of high density lipoprotein cholesterol (HDL-C) as an anti-inflammatory and C reactive protein (CRP) as inflammatory properties on the pathogenesis of heart failure were reported. At present, the clinical significance of the HDL-C/CRP ratio in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. METHODS AND RESULTS:We examined the data on 796 consecutive HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT-HFpEF registry, a prospective, multicentre observational study. We calculated the HDL/CRP ratios and evaluated the relationship between the values and clinical outcomes, including degree of cardiac function. The mean follow-up duration was 420 ± 346 days. All-cause death occurred in 118 patients, of which 51 were cardiac deaths. HDL/CRP ≤ 4.05 was independently and significantly associated with all-cause death (odds ratio = 1.84, 95% CI: 1.06-3.20, P = 0.023), and HDL/CRP ≤ 3.14 was associated with cardiac death by multivariate Cox proportional hazard analysis (odds ratio = 2.86, 95% CI: 1.36-6.01, P = 0.003). HDL-C/CRP ratio significantly correlated with the product of the left atrial volume and left ventricular mass index as well as the tricuspid annular plane systolic excursion by multiple regression analysis (standardized beta-coefficient = -0.085, P = 0.034 and standardized beta-coefficient = 0.081, P = 0.044, respectively). CONCLUSIONS:HDL-C/CRP ratio was a useful marker for predicting all-cause death and cardiac death and correlated with left ventricular diastolic function and right ventricular systolic function in HFpEF patients.