logo logo
TSH enhancement of FT4 to FT3 conversion is age dependent. Strich David,Karavani Gilad,Edri Shalom,Gillis David European journal of endocrinology OBJECTIVE:We previously reported increasing free T3 (FT3) to free T4 (FT4) ratios as thyroid-stimulating hormone (TSH) increases within the normal range in children. It is not known if this phenomenon is age-related among humans, as previously reported in rats. This study examines the relationships between TSH and FT3/FT4 ratios in different ages. DESIGN:Retrospective examination of thyroid tests from patients without thyroid disease from community clinics. METHODS:Free T3, free T4, and TSH levels from 527 564 sera collected from patients aged 1 year or greater were studied. Exclusion criteria were the following: missing data, TSH greater than 7.5mIU/L, and medications that may interfere with thyroid hormone activity. A total of 27 940 samples remaining after exclusion were stratified by age. Samples with available anthropometric data were additionally stratified for body mass index (BMI). Correlations of TSH to FT4, FT3, and FT3/FT4 ratios by age group were examined. RESULTS:Up to age 40, for each increasing TSH quartile, FT3 and the FT3/FT4 ratio increased and FT4 decreased significantly (for both FT3, FT4 and FT3/FT4 ratio, P<0.05 for every TSH quartile when compared with the 1st quartile, except FT3 in the 30-40 age group). In older age groups, increasing TSH was not associated with increased FT3/FT4 ratio. CONCLUSION:As TSH levels increase, FT3/FT4 ratios increase until age 40, but this differential increase does not occur in older age groups. This may reflect a decrease in thyroxine (T4) to triiodothyronine (T3) conversion with age, which may be part of the aging process. 10.1530/EJE-16-0007
Value of FT3/FT4 Ratio in Prognosis of Patients With Heart Failure: A Propensity-Matched Study. Frontiers in cardiovascular medicine Aims:Abnormal thyroid hormone secretions can alter the manifestation and prognosis of cardiovascular disease. To assess the effect of the free triiodothyronine (FT3)/free thyroxine (FT4) ratio on the prognosis of patients with heart failure (HF), we performed a propensity-matched study on patients with well-balanced baseline characteristics. Methods:Overall, 8,887 patients with HF were divided into two groups according to the FT3/FT4 ratio. Propensity scores were calculated from each patient. A cohort comprising 2,164 pairs with high or low ratios and with 34 well-balanced baseline characteristics was then assembled. The endpoints were Cardiovascular (CV) mortality and all-cause mortality. The correlation between FT3/FT4 ratio and prognosis was assessed using matched Cox regression analyses. The mean follow-up was 3.3 years. Results:In the full pre-match cohort, 3,710 (41.7%) patients died, with 2,581 (29.0%) cases of CV mortality. In the matched-pair cohort, all-cause mortality occurred in 923 (1,238/10,000 person-years of follow-up) patients with a high ratio and 1,036 (1,484/10,000 person-years) patients with a low ratio, resulting in a matched HR of 0.841 (95% CI: 0.769-0.919; < 0.001). For CV mortality, the result was 638 (856/10,000 person-years) and 714 (1,023/10,000 person-years) patients, respectively, resulting in a matched HR of 0.844 (95% CI: 0.759-0.940; < 0.001). Subgroup analysis revealed that a low FT3/FT4 ratio had a greater predictive value for all-cause and CV mortality in elderly or male patients and in patients with coronary artery disease (CAD), hypertension, diabetes mellitus, HFmrEF, or HFpEF. Conclusions:A low FT3/FT4 ratio is valuable for predicting CV mortality and all-cause mortality in patients with HF. 10.3389/fcvm.2022.859608
Low FT3/FT4 Ratio Is Linked to Poor Prognosis of Acute Myocardial Infarction in Euthyroid Patients with Type 2 Diabetes Mellitus. Journal of clinical medicine This is an observational, retrospective, single-center study aimed to determine whether the free triiodothyronine (FT3) to free thyroxine (FT4) ratio was related to acute myocardial infarction (AMI) prognosis in individuals with type 2 diabetes mellitus (T2DM). A total of 294 euthyroid T2DM patients with new-onset AMI were enrolled. FT3/FT4 ratio tertiles were used to categorize patients into Group 1 (FT3/FT4 ≥ 4.3), Group 2 (3.5 ≤ FT3/FT4 < 4.3), and Group 3 (FT3/FT4 < 3.5). Major adverse cardiac events (MACE), including nonfatal myocardial infarction, target vessel revascularization (TVR), and cardiac mortality, served as the primary endpoint. Group 3 demonstrated a considerably higher incidence of MACE than the other two groups over the average follow-up duration of 21 ± 6.5 months (all p < 0.001). Multivariable Cox regression analysis showed that a low FT3/FT4 ratio was an independent risk factor for MACE after AMI (Group 1 as a reference; Group 2: hazard ratio [HR] 1.275, 95% confidence interval [CI]: 0.563−2.889, p = 0.561; Group 3: HR 2.456, 95% CI: 1.105−5.459, p = 0.027). Moreover, the area under the receiver-operating characteristic curve (AUC) indicates a good predictive value of FT3/FT4 ratio for MACE (AUC = 0.70). Therefore, in T2DM patients with AMI, a low FT3/FT4 ratio was strongly linked to poor prognosis. 10.3390/jcm11216530
FT3/FT4 ratio is correlated with all-cause mortality, cardiovascular mortality, and cardiovascular disease risk: NHANES 2007-2012. Frontiers in endocrinology Background:Thyroid hormones play a vital role in maintaining the homeostasis of the cardiovascular system. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral sensitivity of thyroid hormones. There is no study to investigate its relationship with death and cardiovascular disease (CVD) in the general population. Methods:This retrospective cohort study involved 8,018 participants with measured thyroid function and no prior thyroid disease who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015. Results:During a median of 87 months of follow-up, we observed 699 all-cause deaths, including 116 cardiovascular deaths. In multivariate adjusted models, higher free thyroxine (FT4) was linked to increased all-cause mortality (HR, 1.15 per SD; 95% CI, 1.09-1.22), cardiovascular mortality (HR, 1.18 per SD; 95% CI, 1.01-1.39), and CVD risk (HR, 1.17 per SD; 95% CI, 1.08-1.27). Higher free triiodothyronine (FT3) was linked to decreased all-cause mortality (HR 0.81 per SD; 95% CI, 0.70-0.93). Higher FT3/FT4 ratio was linked to decreased all-cause mortality (HR, 0.77 per SD; 95% CI, 0.69-0.85), cardiovascular mortality (HR, 0.79 per SD; 95% CI, 0.62-1.00), and CVD risk (HR, 0.82 per SD; 95% CI, 0.74-0.92). The FT3/FT4 ratio stratified findings were broadly consistent with the overall results. Conclusions:FT3, FT4, and the FT3/FT4 ratio were all independent predictors of all-cause death. FT4 and the FT3/FT4 ratio, but not FT3, were independent predictors of cardiovascular mortality and CVD risk. Along with FT3 and FT4, we should pay equal attention to the FT3/FT4 ratio in the general population. 10.3389/fendo.2022.964822
FT3 IS HIGHER IN MALES THAN IN FEMALES AND DECREASES OVER THE LIFESPAN. Strich David,Karavani Gilad,Edri Shalom,Chay Cherut,Gillis David Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists OBJECTIVE:Normal changes in free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels over the lifespan and differences between sexes are not well documented, mainly because even the largest-scale studies available include relatively small cohorts. The aim of this study was to define age-related trends including sex differences based on reliable data. METHODS:A large database including serum thyroid tests drawn in community clinics was studied. FT3, FT4, and TSH levels from 527,564 sera samples taken from patients age 1 year or greater were included. After highly extensive exclusion criteria applied to remove all samples that may have been taken from unhealthy people, 27,940 samples remained. These were stratified by decades of age and by sex. RESULTS:FT3 decreases throughout life, significantly more so among females, with equalization between sexes with greater age. FT4 declines to a lesser extent, also more among females than among males. Among the very old, females have higher levels of FT4. In contrast, TSH declines until age 50 and then increases slightly in both sexes. CONCLUSION:This study provides reliable data regarding trends in hormonal levels by age and sex, with the major finding being higher FT3 in males throughout life except in the very young and very old. These results have important implications for diagnosing and treating thyroid conditions. ABBREVIATIONS:ANOVA = analysis of variance; BMI = body mass index; FT3 = free triiodothyronine; FT4 = free thyroxine. 10.4158/EP171776.OR
Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention. Frontiers in endocrinology Objectives:In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods:A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results:Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion:A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI. 10.3389/fendo.2024.1322969
The Impact of Age- and Sex-Specific Reference Ranges for Serum Thyrotropin and Free Thyroxine on the Diagnosis of Subclinical Thyroid Dysfunction: A Multicenter Study from Japan. Thyroid : official journal of the American Thyroid Association Reference ranges for serum thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) established without considering age- and sex-based differences are currently used to evaluate thyroid function. Therefore, we investigated age- and sex-based differences in serum TSH and thyroid hormone levels in euthyroid individuals. We performed cross-sectional analyses of retrospective data collected from two Japanese institutions. We estimated sex-specific 95% reference ranges for TSH and fT4 according to age strata. We included data from 14,860 participants undergoing screening with a Siemens thyroid testing kit and 8,132 participants undergoing screening with an Abbott kit during annual health check-ups at Takasaki Hidaka Hospital. In addition, 515 participants visiting a specialized thyroid-focused hospital were evaluated using Tosoh kits. The median TSH level of women in their 30s was 1.5 mIU/L (2.5th percentile, 0.5; 97.5th percentile, 4.6) using the Siemens kit, while that of women in their 60s was 1.9 (0.7-7.8) mIU/L. The corresponding levels were lower in men; the age-associated increase was small. The median serum fT4 level of men in their 30s was 1.3 (1.0-1.7) ng/dL and that of men in their 60s was 1.2 (1.0-1.6) ng/dL. These levels gradually but significantly decreased with age. fT4 levels in women were lower than those in men and remained consistent with age. Serum fT3 levels were significantly higher in men than in women and gradually but significantly decreased with age. The Abbott and Tosoh kits showed similar results. When using the Siemens kit, ∼60% (216/358) of women diagnosed with subclinical hypothyroidism using manufacturer-recommended reference ranges had normal results when age- and sex-specific reference ranges were applied, demonstrating the high percentage of overdiagnosis, especially in those aged ≥60 years. Conversely, some middle-aged individuals with normal thyroid function were reassessed and classified as having subclinical hyperthyroidism by age- and sex-specific reference ranges. Age- and sex-specific reference ranges should be used to avoid over- and underdiagnosis of subclinical thyroid dysfunction and appropriate therapies. 10.1089/thy.2022.0567
Low Free Triiodothyronine Level as a Predictor of Cardiovascular Events and All-Cause Mortality in Patients Undergoing Hemodialysis: The DREAM Cohort. Yamazaki Yuko,Shoji Tetsuo,Miyashima Masako,Nagata Yuki,Kakutani Yoshinori,Ochi Akinobu,Morioka Tomoaki,Nakatani Shinya,Mori Katsuhito,Tsujimoto Yoshihiro,Emoto Masanori Journal of atherosclerosis and thrombosis AIM:Low T3 syndrome is characterized by low serum triiodothyronine (T3) levels without elevation of thyroid-stimulating hormone (TSH) in patients without apparent thyroid disease, which is known to be associated with worse clinical outcomes in various populations including those with kidney failure. In this study, we examined whether low free T3 (FT3) levels are independent predictor of cardiovascular disease (CVD) events in patients undergoing hemodialysis. METHODS:This was a prospective cohort study of patients with chronic kidney disease undergoing hemodialysis. From the total of 518 patients, we excluded patients with treated or untreated hyperthyroidism or hypothyroidism and those treated with corticosteroids. RESULTS:We analyzed data from 438 eligible patients. During the 5-year follow-up, 154 new CVD events and 86 all-cause deaths were recorded. Kaplan-Meier analysis showed that lower FT3 levels were associated with higher risks for new cardiovascular events and all-cause death. This inverse association of FT3 and new CVD events remained significant after adjustment for age, sex, duration of hemodialysis, diabetic kidney disease, hypertension, dyslipidemia, and smoking; however, it was no longer significant after further adjustment for prior CVD or N-terminal fragment of probrain natriuretic peptide (NT-proBNP). FT3 did not show an independent association with all-cause mortality. CONCLUSIONS:Our results indicate that low FT3 status is not an independent predictor of new CVD events and that the following factors are closely associated: prior CVD, low FT3 and high NT-proBNP levels at present, and future risk of new CVD events in hemodialysis patients. 10.5551/jat.60624
Low Free Triiodothyronine Predicts 3-Month Poor Outcome After Acute Stroke. Suda Satoshi,Shimoyama Takashi,Nagai Koichiro,Arakawa Masafumi,Aoki Junya,Kanamaru Takuya,Suzuki Kentaro,Sakamoto Yuki,Takeshi Yuho,Matsumoto Noriko,Nishiyama Yasuhiro,Nito Chikako,Mishina Masahiro,Kimura Kazumi Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association BACKGROUND AND PURPOSE:The association between thyroid hormone levels and long-term clinical outcome in patients with acute stroke has not yet been thoroughly studied. The purpose of the present study was to test the hypothesis that thyroid hormone levels are associated with 3-month functional outcome and mortality after acute stroke. METHODS:We retrospectively analyzed 702 consecutive patients with acute stroke (251 women; median age, 73 years) who were admitted to our department. General blood tests, including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were performed on admission. Neurological severity was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores on admission and modified Rankin Scale (mRS) scores at 3 months after stroke onset. Poor outcome was defined as an mRS score of 3-5 or death. The impact of thyroid function on 3-month outcome was evaluated using multiple logistic regression analysis. RESULTS:Poor functional outcome was observed in 295 patients (42.0%). Age (P < .0001), female sex (P < .0001), admission NIHSS score (P < .0001), smoking (P = .0026), arterial fibrillation (P = .0002), preadmission mRS (P < .0001), estimated glomerular filtration rate (P = .0307), and ischemic heart disease (P = .0285) were significantly associated with poor functional outcome, but no relationship between FT4, TSH, and poor functional outcome was found. A multivariate logistic regression analysis showed that low FT3 values (<2.00 pg/mL) were independently associated with poor functional outcome (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.60-6.24) and mortality (OR, 2.55; 95% CI, 1.33-4.91) at 3 months after stroke onset. CONCLUSIONS:Our data suggest that a low FT3 value upon admission is associated with a poor 3-month functional outcome and mortality in patients with acute stroke. 10.1016/j.jstrokecerebrovasdis.2018.06.009
The neutrophil lymphocyte ratio in coronary heart disease. Balta Sevket,Demirkol Sait,Aparcı Mustafa,Celik Turgay,Ozturk Cengiz International journal of cardiology 10.1016/j.ijcard.2014.06.098
Clinical Value of Platelet Indices in Premature Coronary Artery Disease. International heart journal Platelets play an important role in the pathophysiology of coronary artery disease. However, the clinical value of platelet indices in premature coronary heart disease remains largely unknown.Consecutive patients referred for coronary angiography were evaluated (n = 1675). Patients were stratified into premature coronary heart disease (n = 679, age < 55 for male and age < 65 for female), late-onset coronary heart disease (n = 772, age ≥ 55 for male and age ≥ 65 for female), and control (n = 224, age < 55 for male and age < 65 for female). Their clinical and laboratory parameters were collected. The relationship between platelet indices and premature coronary artery disease was analyzed.In univariate analysis, platelet indices showed no significant association with the presence of premature coronary heart disease (P > 0.05). After adjustment for traditional risk factors, mean platelet volume (0.823 [0.683-0.993], P = 0.042) and platelet-large cell ratio (0.976 [0.954-0.999], P = 0.040) were negatively correlated with the presence of premature coronary heart disease. The platelet-to-lymphocyte ratio was statistically significant among different numbers of coronary lesions (P = 0.035). In subgroup analysis, platelet-large cell ratio (1.190 [1.010-1.403], P = 0.038) was an independent risk factor of coronary restenosis after percutaneous coronary intervention.Platelet indices were associated with the prevalence, severity, and coronary restenosis after percutaneous coronary intervention suggesting their possible clinical application in premature coronary heart disease. 10.1536/ihj.22-442
Systemic immune-inflammation index predicts the severity of coronary stenosis in patients with coronary heart disease. Liu Yehong,Ye Ting,Chen Liang,Jin Tianhui,Sheng Ying,Wu Gangyong,Zong Gangjun Coronary artery disease BACKGROUND:Coronary atherosclerosis is a systemic chronic inflammatory disease with variable occurrence and progression. Some laboratory parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein (CRP) level, are used to evaluate the degree of inflammation and the severity of coronary artery disease (CAD). The neutrophil*platelet/lymphocyte is a novel systemic immune-inflammation index (SII), and its relationship with the development and severity of CAD is unclear. OBJECTIVE:To investigate the association between the SII and the severity of CAD. METHODS:Three-hundred and ninety-five patients who underwent coronary angiography were enrolled; among whom, 285 patients were included in the CAD group and 110 patients were included in the non-CAD group according to the WHO guidelines. Patients with CAD were further divided according to the Gensini score into the severe coronary stenosis group and the mild coronary stenosis group. The SII was calculated using the following formula: neutrophil*platelet/lymphocyte. RESULTS:When the cutoff value of the SII was set at 439.44, the predictive power of CAD was the highest, with a sensitivity and specificity of 64.6 and 68.2%, respectively. When the cutoff value of the SII was set at 652.83, the predictive power of severe coronary stenosis was the highest, with a sensitivity and specificity of 71.0 and 86.0%, respectively. The area under the curve of the SII in predicting severe coronary stenosis was greater than that of the NLR, PLR and CRP level. CONCLUSION:The SII is an independent risk factor for the occurrence and severity of CAD. 10.1097/MCA.0000000000001037
Genetically Predicted Neutrophil-to-Lymphocyte Ratio and Coronary Artery Disease: Evidence From Mendelian Randomization. Circulation. Genomic and precision medicine 10.1161/CIRCGEN.121.003553
Leukocyte count and coronary heart disease: implications for risk assessment. Madjid Mohammad,Awan Imran,Willerson James T,Casscells S Ward Journal of the American College of Cardiology Inflammation is a key feature of atherosclerosis and its clinical manifestations. The leukocyte count is a marker of inflammation that is widely available in clinical practice. This paper reviews the available epidemiologic evidence for a relationship between the leukocyte count and coronary heart disease (CHD). Numerous epidemiologic and clinical studies have shown leukocytosis to be an independent predictor of future cardiovascular events, both in healthy individuals free of CHD at baseline and in patients with stable angina, unstable angina, or a history of myocardial infarction. This relationship has been observed in prospective and retrospective cohort studies, as well as in case-control studies. It is strong, consistent, temporal, dose-dependent, and biologically plausible. The relationship persists after adjustment for multiple CHD risk factors, including smoking. Elevated differential cell counts, including eosinophil, neutrophil, and monocyte counts, also predict the future incidence of CHD. Leukocytosis affects CHD through multiple pathologic mechanisms that mediate inflammation, cause proteolytic and oxidative damage to the endothelial cells, plug the microvasculature, induce hypercoagulability, and promote infarct expansion. In summary, leukocytosis has been consistently shown to be an independent risk factor and prognostic indicator of future cardiovascular outcomes, regardless of disease status. The leukocyte count is inexpensive, reliable, easy to interpret, and ordered routinely in inpatient and outpatient settings. However, its diagnostic and prognostic utility in CHD is widely unappreciated. Further studies are needed to assess the true impact of leukocytosis on CHD, compare it with other inflammatory markers such as C-reactive protein and lipoprotein phospholipase A(2) levels, and promote its use in CHD prediction. 10.1016/j.jacc.2004.07.056
Prognostic impact of monocyte-to-lymphocyte ratio in coronary heart disease: a systematic review and meta-analysis. The Journal of international medical research OBJECTIVE:Inflammatory biomarkers are novel tools to assess the prognosis of different cardiovascular diseases. We evaluated the impact of the monocyte-to-lymphocyte ratio (MLR) on clinical outcomes in patients with coronary heart disease (CHD). METHODS:We systematically screened English-language articles in PubMed, Scopus, and Web of Science to 31 August 2022. Relevant articles reporting the MLR and its association with clinical outcomes (major adverse cardiovascular events (MACE), coronary artery disease (CAD) severity, mortality, cardiac rupture, subclinical CAD, acute coronary syndrome (ACS) prediction, thin-cap fibroatheroma, no-reflow phenomenon, MLR-related differences in percutaneous coronary intervention, heart failure hospitalization, and depression) in patients with CHD were collected for further analysis. RESULTS:Nineteen articles were selected. The mean MLR was 0.34. A higher MLR was significantly associated with an increased risk of MACE among patients with CHD. The MLR was an independent predictor of MACE in patients with ACS. No significant association was found for CAD severity. A complementary analysis was not performed because of few studies focusing on the other predefined endpoints. CONCLUSIONS:The MLR is a simple and widely available tool to predict MACE in patients with CHD. This biomarker can be utilized in emergency settings to prioritize high-risk patients and optimize therapeutic interventions. 10.1177/03000605231204469
Predictive value of in-hospital white blood cell count in Chinese patients with triple-vessel coronary disease. Zhao Xueyan,Jiang Lin,Xu Lianjun,Tian Jian,Xu Yujun,Zhao Yanyan,Feng Xinxing,Wu Yajie,Zhang Yin,Wang Dong,Sun Kai,Xu Jingjing,Liu Ru,Xu Bo,Zhao Wei,Hui Rutai,Gao Runlin,Song Lei,Yuan Jinqing European journal of preventive cardiology AIMS:The predictive value of white blood cells in triple-vessel coronary artery disease (TVD) remains unclear. This study aimed to examine the relationship between WBC counts and long-term prognosis of TVD. METHODS:A total of 8943 consecutive patients with triple-vessel coronary artery disease were enrolled from April 2004 to February 2011. The primary endpoint was all-cause death and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs; a composite of all-cause death, myocardial infarction or stroke). RESULTS:After a median of 7.5 years of follow-up, 7678 patients were included in the final analysis. Multivariable analysis showed that the white blood cell count was an independent predictor of death (hazard ratio: 1.04, p < 0.01) and MACCE (hazard ratio: 1.03, p = 0.02). In white blood cell differential analysis, increased monocytes (hazard ratio: 1.93, p = 0.001) and eosinophils (hazard ratio: 1.82, p < 0.01), and decreased lymphocytes (hazard ratio: 0.89, p = 0.02) were independent predictors of death. Increased monocytes (hazard ratio: 1.62, P = 0.002) and eosinophils (hazard ratio: 1.55, p < 0.01) were independent predictors of MACCE. A combination of monocyte, lymphocyte and eosinophil counts with the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score improved the predictive value for mortality (area under the curve from 0.569 to 0.611; integrated discrimination improvement = 0.012; net reclassification improvement = 0.299) and improved slightly with SYNTAX score II (all p < 0.05). CONCLUSION:Total and differential white blood cell counts are independent prognostic factors of long-term mortality and MACCE in triple-vessel coronary artery disease. A combination of monocyte, lymphocyte and eosinophil counts improved the predictive value for mortality with the SYNTAX score, and improved it slightly with SYNTAX score II. 10.1177/2047487319826398
Platelets, coronary heart disease, and stress. Brydon Lena,Magid Kesson,Steptoe Andrew Brain, behavior, and immunity Coronary heart disease is the leading cause of death in Western society, and its development is associated with chronic stress and other psychosocial factors. Atherosclerosis, the disorder underlying this disease, is an inflammatory process in which leukocytes interact with structurally intact but dysfunctional endothelium of the arteries. Platelets play a key role in this process by binding to leukocytes and promoting their recruitment to the endothelium. Platelet-leukocyte interactions also stimulate the release of pro-inflammatory and pro-thrombotic factors which promote atherosclerosis. Elevated circulating levels of platelet-leukocyte aggregates have been reported in cardiac patients and in individuals of low socioeconomic status, a factor associated with chronic psychological stress. Increased platelet activation has also been observed in individuals prone to depression or hostility, and in people subject to high levels of work stress. Acute psychological stress increases circulating platelet-leukocyte aggregates in healthy individuals and this effect is prolonged in cardiac patients. Platelet activation may be a mechanism linking psychosocial stress with increased coronary risk, and may also play a role in the emotional triggering of acute coronary syndromes in patients with advanced coronary disease. 10.1016/j.bbi.2005.08.002
Leukocyte Telomere Length as a Molecular Biomarker of Coronary Heart Disease. Genes BACKGROUND:This work is a review of preclinical and clinical studies of the role of telomeres and telomerase in the development and progression of coronary heart disease (CHD). MATERIALS AND METHODS:A search for full-text publications (articles, reviews, meta-analyses, Cochrane reviews, and clinical cases) in English and Russian was carried out in the databases PubMed, Oxford University Press, Scopus, Web of Science, Springer, and E-library electronic library using keywords and their combinations. The search depth is 11 years (2010-2021). RESULTS:The review suggests that the relative leukocyte telomere length (LTL) is associated with the development of socially significant and widespread cardiovascular diseases such as CHD and essential hypertension. At the same time, the interests of researchers are mainly focused on the study of the relative LTL in CHD. CONCLUSIONS:Despite the scientific and clinical significance of the analyzed studies of the relative length of human LTL as a biological marker of cardiovascular diseases, their implementation in real clinical practice is difficult due to differences in the design and methodology of the analyzed studies, as well as differences in the samples by gender, age, race, and ethnicity. The authors believe that clinical studies of the role of the relative length of leukocyte telomeres in adult patients with coronary heart disease are the most promising and require large multicenter studies with a unified design and methodology. 10.3390/genes13071234
NPAS4 Polymorphisms Contribute to Coronary Heart Disease (CHD) Risk. Cardiovascular toxicology As genetic inheritance is an inevitable risk factor in the development of coronary heart disease (CHD), it is critical to identify the polymorphisms of CHD risk. This study explored whether the NPAS4 polymorphisms are related to the CHD risk in the Chinese Han population. Five SNPs in NPAS4 were genotyped using Agena Mass ARRAY from 499 CHD and 500 controls. RT-PCR detected the NPAS4 expression levels in peripheral blood mononuclear cells from 50 CHD and 50 controls. χ test compared the distributions of gender, allele and genotypes frequencies between cases and controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). MDR analyzed the SNP-SNP interactions on risk of CHD. U test compared the differences in gene expression between different groups. The results showed that rs4466842 was correlated with an increased CHD risk in overall, males and age ≤ 60; rs117186164 and rs12785321 were significantly related to an increased CHD risk in male and age ≤ 60, respectively; haplotype AC was significantly correlated with an increased CHD risk. SNP-SNP interactions results showed that the best model was the four-locus model was the combination of rs117770654, rs117957381, rs12785321, and rs4466842 (CVC = 10/10, Testing Sensitivity = 0.647). The expression levels of NPAS4 in the case group (0.365 ± 0.139) were significantly lower than that in the control group (0.782 ± 0.224) (P < 0.001). The results revealed that SNPs in NPAS4 may play an important role in the occurrence and development of CHD. 10.1007/s12012-022-09735-9
Interleukin‑37 is increased in peripheral blood mononuclear cells of coronary heart disease patients and inhibits the inflammatory reaction. Li Huimin,Shen Chen,Chen Bingni,Du Jing,Peng Bin,Wang Wei,Chi Fanwu,Dong Xiaoqiang,Huang Zhong,Yang Chao Molecular medicine reports It has been universally acknowledged that interleukin‑37 (IL‑37) has an immunosuppressive effect on various inflammatory disorders. However, whether IL‑37 participates in the acute inflammation associated with coronary heart disease (CHD) has not yet been clarified. In the present study, the association between the serum levels of IL‑37 and the clinical indexes of CHD were analysed. In addition, the anti‑inflammatory effects of IL‑37 on peripheral blood mononuclear cells (PBMCs) were studied in CHD patients. PBMCs from 46 healthy controls (HCs) and 92 CHD patients were cultured in vitro and stimulated using the recombinant IL‑37 protein. The protein levels, as well as the mRNA expression of inflammatory cytokines (TNF‑α, IL‑1β, IL‑6, and IL‑17) were analysed by enzyme‑linked immunosorbent assay (ELISA) and real‑time polymerase chain reaction (RT‑PCR). Spearman's correlation test was performed to examine the association between the serum level of IL‑37 and the levels of pro‑inflammatory cytokines, certain clinical indexes, and disease activity during CHD. Compared to the HCs, the CHD patients, especially those with acute myocardial infarction, exhibited higher levels of IL‑37 in their PBMCs and sera. Serum levels of IL‑37 were associated with the levels of IL‑17, IL‑6, and TNF‑α, and clinical indexes such as the left ventricular ejection fraction (LVEF), amino‑N‑terminal pro‑plasma brain natriuretic peptide (NT‑proBNP) levels, and cardiac troponin T (cTnT) levels in CHD patients. Compared to the HC group, the production of inflammatory cytokines such as IL‑17, IL‑6, TNF‑α, and IL‑1β increased in the PBMCs of CHD patients and significantly decreased after the stimulation of the cells with recombinant IL‑37. The IL‑37 levels in CHD patients were high, and were correlated with the levels of CHD‑related pro‑inflammatory cytokines and disease activity. Notably, the expression of CHD‑related pro‑inflammatory cytokines in the PBMCs of CHD patients decreased following the stimulation of the cells with recombinant IL‑37, indicating that IL‑37 exerts anti‑inflammatory effects during CHD. 10.3892/mmr.2019.10805
Association between sensitivity to thyroid hormones and dyslipidemia in patients with coronary heart disease. Endocrine BACKGROUND:Thyroid hormones affect lipid metabolism via central and peripheral regulation. However, there have been few studies on the association between thyroid hormone sensitivity and dyslipidemia. We aimed to investigate the association between thyroid hormone sensitivity and dyslipidemia in patients with coronary heart disease (CHD). METHODS:A total of 31,678 patients with CHD were included in this large multicenter retrospective study. Central thyroid hormone sensitivity was evaluated using the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyroid-stimulating hormone index (TSHI), and thyrotropin thyroxine resistance index (TT4RI); peripheral thyroid hormone sensitivity was assessed by the ratio of free triiodothyronine (FT3)/free thyroxine (FT4). Logistic regression analysis was used to analyze the association between thyroid hormone sensitivity and dyslipidemia. RESULTS:Among 31,678 participants, 21,648 (68.34%) had dyslipidemia. In the multi-adjusted models, the risk of dyslipidemia was positively correlated with TFQI (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.03-1.05), PTFQI (OR: 1.09; 95% CI: 1.06-1.12), TSHI (OR: 1.08; 95% CI: 1.06-1.11), and TT4RI (OR: 1.08; 95% CI: 1.05-1.11). Conversely, the risk of dyslipidemia was negatively correlated with FT3/FT4 (OR: 0.94; 95% CI: 0.92-0.97). In stratified analyses, the association between thyroid hormone sensitivity and dyslipidemia was statistically significant for different sexes, glucose levels, and blood pressure states. CONCLUSION:There is a significant association between sensitivity to thyroid hormones and dyslipidemia, regardless of sex, glucose level, or blood pressure. Graphical abstract. 10.1007/s12020-022-03254-x
Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Blood Glucose in Coronary Heart Disease. Frontiers in endocrinology Context:Thyroid hormones influence glucose homeostasis through central and peripheral regulation. To date, the association between thyroid hormone sensitivity and elevated blood glucose (EBG) in patients with coronary heart disease (CHD) remains unknown. The purpose of this study was to investigate the association between thyroid hormone sensitivity and risk of EBG in patients with CHD, and to further explore their association in different sexes and ages. Methods:This large multicenter retrospective study included 30,244 patients with CHD (aged 30-80 years) between 1 January 2014 and 30 September 2020. Parameters representing central and peripheral sensitivity to thyroid hormones were calculated. Central sensitivity to thyroid hormones was assessed by calculating the Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), and Thyrotropin Thyroxine Resistance Index (TT4RI), and Parametric Thyroid Feedback Quantile-based Index (PTFQI); peripheral sensitivity to thyroid hormones was evaluated using the ratio of free triiodothyronine (FT3) /free thyroxine (FT4). Taking normal glucose tolerance (NGT) as a reference, logistic regression was used to analyse the relationship between central and peripheral thyroid hormone sensitivity and EBG in patients with CHD. Results:Among the 30,244 participants, 15,493 (51.23%) had EBG. The risk of EBG was negatively correlated with TSHI (OR: 0.91; 95%CI: 0.91 to 0.92; < 0.001), TT4RI (OR: 0.99; 95% CI: 0.99 to 0.99; <0.001), TFQI (OR: 0.82; 95%CI: 0.80 to 0.84; 0.001) and PTFQI (OR: 0.76; 95%CI: 0.74 to 0.78; <0.001). Compared to males and patients aged 60 and below, the OR value for EBG was lower in females and in patients aged over 60 years old. Conversely, EBG risk was positively associated with FT3/FT4 (OR: 1.08; 95% CI: 1.07 to 1.09; 0.001) and in the sex-categorized subgroups, males had higher OR values than females. Conclusions:This study showed that thyroid hormone sensitivity is significantly associated with EBG in patients with CHD. This association is higher in females than in males, and the association in those aged over 60 years old is higher than that in patients aged 60 years and below. 10.3389/fendo.2022.895843
Leukocytes and coronary heart disease. Hoffman Michael,Blum Arnon,Baruch Roni,Kaplan Eli,Benjamin Moshe Atherosclerosis Inflammation has been demonstrated to be an important risk factor for the development of cardiovascular events. Patients with elevated white blood cell counts have been shown to be in a higher risk of developing acute myocardial infarction and acute coronary and vascular events. We review the clinical data of high white blood cell counts and the prognosis, and demonstrate several possible mechanisms. It is possible that measuring white blood cell count and subpopulations could be used for a better way of risk stratification of patients admitted with acute vascular events. 10.1016/s0021-9150(03)00164-3