Chinese Coronary Artery Disease Patients Research Articles

Association of genetic variations of 3′-UTR in clopidogrel pharmacokinetic-relevant genes with clopidogrel response in Han Chinese patients with coronary artery disease

Dual antiplatelet therapy with aspirin and clopidogrel has reduced ischemic vascular events significantly. Genetic influence, especially those in clopidogrel pharmacokinetic-relevant genes partially accounts for interindividual pharmacodynamic variability of clopidogrel. However, most studies have concentrated on the genetic variations in introns, exons, or promoters of the candidate genes, and the association between genetic variations in 3′-UTR in clopidogrel pharmacokinetic-relevant genes and clopidogrel response is unknown. In our study, ten different algorithms were applied to pick potential miRNAs targeting the clopidogrel pharmacokinetic-relevant genes. Furthermore, the correlation between miRNA expression profiles and mRNA expression of corresponding clopidogrel pharmacokinetic-relevant genes was analyzed. Through comprehensive analysis, including bioinformatics prediction and correlation analysis of miRNA and mRNA expression profiles, miR-218–5p and miR-506–5p were supposed to regulate the expression of PON1 via binding with its 3′-UTR. Moreover, PON1 rs854551 and rs854552 were located in miRNA recognizing sequences and may serve as potential miRSNPs possibly affecting PON1 expression. The rs854552 polymorphism was genotyped and platelet reactivity index (PRI) indicative of clopidogrel response was measured in 341 Chinese coronary artery disease (CAD) patients 24 h after administration of 300 mg clopidogrel. Our results showed that PON1 rs854552 had a significant influence on PRI in CAD patients, especially in patients with CYP2C19 extensive metabolic phenotype. In conclusion, PON1 rs854552 polymorphisms may affect clopidogrel response. Bioinformatics prediction followed by functional validation could aid in decoding the contribution of unexplained variations in the 3′-UTR in drug-metabolizing enzymes on clopidogrel response.

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus

BackgroundCompelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM).ObjectiveThis study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM.MethodsSerum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models.ResultsThis cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05).ConclusionsT2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

High-normal serum bilirubin decreased the risk of lower limb atherosclerosis in type 2 diabetes: a real-world study

BackgroundBilirubin has been found to protect against overt atherosclerotic diseases, but to date, few studies have investigated the effects of bilirubin especially within the normal range on lower limb atherosclerosis. Therefore, we aimed to assess the associations of bilirubin within normal limits including total bilirubin (TB), conjugated bilirubin (CB) and unconjugated bilirubin (UCB) with lower limb atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM).Methods7284 T2DM patients with normal levels of serum bilirubin were included in this cross-sectional, real-world study. Patients were divided into quintiles by TB levels (< 8.7, 8.7-10.19, 10.20-11.99, 12-13.99, > 13.99 µmol/L). Lower limb ultrasonography was conducted to detect lower limb plaque and stenosis. The association between serum bilirubin and lower limb atherosclerosis was explored by multiple logistic regression.ResultsA remarkable decrease in the prevalence of lower limb plaque (77.5, 75.3, 70.7, 71.7 and 67.9%) and stenosis (21.1, 17.2, 13.3, 13.0 and 12.0%) was observed across the TB quintiles. Multivariable regression analysis showed that serum TB levels were negatively correlated with higher risks of lower limb plaque and stenosis, both as a continuous variable [OR (95%CI): 0.870 (0.784–0.964), p = 0.008 for plaque; and 0.835 (0.737–0.946), p = 0.005 for stenosis] and as categorized in quintiles (p = 0.015 and 0.016 for plaque and stenosis). Interestingly, serum CB levels were only negatively correlated with lower limb stenosis [OR (95%CI): 0.767 (0.685–0.858), p < 0.001], whereas serum UCB levels were only negatively associated with lower limb plaque [ OR (95%CI): 0.864 (0.784–0.952), p = 0.003] after a fully-adjusted analysis. Furthermore, serum CRP was significantly decreased across the TB quintiles and negatively associated with serum TB (r = -0.107, p < 0.001), CB (r = -0.054, p < 0.001), and UCB (r = -0.103, p < 0.001).ConclusionsHigh-normal serum bilirubin levels were independently and significantly related to reduced risks of lower limb atherosclerosis in T2DM patients. Furthermore, serum bilirubin levels including TB, CB and UCB were inversely correlated with CRP. These results suggested that higher-normal serum bilirubin may exhibit an anti-inflammatory and protective effect against lower limb atherosclerotic progression in T2DM subjects.

Impact of epicardial adipose tissue volume on hemodynamically significant coronary artery disease in Chinese patients with known or suspected coronary artery disease.

Epicardial adipose tissue (EAT) is directly related to coronary artery disease (CAD), but little is known about its role in hemodynamically significant CAD. Therefore, our goal is to explore the impact of EAT volume on hemodynamically significant CAD. Patients who underwent coronary computed tomography angiography (CCTA) and received coronary angiography within 30 days were retrospectively included. Measurements of EAT volume and coronary artery calcium score (CACs) were performed on a semi-automatic software based on CCTA images, while quantitative flow ratio (QFR) was automatically calculated by the AngioPlus system according to coronary angiographic images. This study included 277 patients, 112 of whom had hemodynamically significant CAD and showed higher EAT volume. In multivariate analysis, EAT volume was independently and positively correlated with hemodynamically significant CAD [per standard deviation (SD) cm3; odds ratio (OR), 2.78; 95% confidence interval (CI), 1.86-4.15; P < 0.001], but negatively associated with QFRmin (per SD cm3; β coefficient, -0.068; 95% CI, -0.109 to -0.027; P = 0.001) after adjustment for traditional risk factors and CACs. Receiver operating characteristics curve analysis demonstrated a significant improvement in predictive value for hemodynamically significant CAD with the addition of EAT volume to obstructive CAD alone (area under the curve, 0.950 vs. 0.891; P < 0.001). In this study, we found that EAT volume correlated substantially and positively with the existence and severity of hemodynamically significant CAD in Chinese patients with known or suspected CAD, which was independent of traditional risk factors and CACs. In combination with obstructive CAD, EAT volume significantly improved diagnostic performance for hemodynamically significant CAD, suggesting that EAT could be a reliable noninvasive indicator of hemodynamically significant CAD.

Low-normal serum unconjugated bilirubin levels are associated with late but not early carotid atherosclerotic lesions in T2DM subjects.

We aimed to examine the association of serum unconjugated bilirubin (UCB) within normal limits with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM). This cross-sectional, real-world study was performed in 8,006 hospitalized T2DM patients including 4,153 men and 3,853 women with normal UCB. The subjects were stratified into quintiles based on serum UCB levels (<6.2, 6.2-7.9, 8.0-8.9, 9.0-10.9, and >10.9 μmol/l, respectively). Carotid atherosclerotic lesions detected by ultrasonography, including carotid intima-media thickness (CIMT), carotid plaque, and stenosis, were compared among the five groups. The associations of serum UCB levels and quintiles with carotid atherosclerotic lesions were also determined by multiple logistic regression. The prevalence of carotid plaque (55.3%, 49.5%, 47.4%, 43.8%, and 37.5%, respectively; p < 0.001 for trend) and stenosis (15.2%, 12.2%, 9.1%, 7.7%, and 5.4%, respectively; p < 0.001 for trend) was progressively lower across the UCB quintiles even after adjusting for age, sex, and duration of diabetes. Results of a fully adjusted multiple logistic regression analysis revealed that serum UCB levels and quintiles were significantly associated with carotid plaque and stenosis. Compared with the subjects in the lowest UCB quintile, the risk of carotid plaque decreased by 25.5%, 28.7%, 33.5%, and 42.8%, and that of carotid stenosis by 24.6%, 37.4%, 44.9%, and 47.3%, respectively, in those from the second to highest UCB quintiles. High serum UCB within the normal range was a protective factor against carotid plaque [odds ratio (OR) 0.810, 95% confidence interval (CI) 0.747-0.878; p < 0.001] and stenosis [OR 0.722, 95% CI 0.647-0.805; p < 0.001]. However, no significant association was observed between serum UCB and CIMT in T2DM patients. Furthermore, C-reactive protein (CRP) levels were significantly higher in the subjects with carotid atherosclerosis than in those without carotid atherosclerosis and clearly decreased across the UCB quintiles. Serum UCB within normal limits is inversely associated with late carotid atherosclerotic lesions including carotid plaque and stenosis but not CIMT, an early carotid atherosclerotic lesion in T2DM patients. High-normal UCB may be protective against carotid atherosclerosis by its anti-inflammation effect, which was indicated by significantly decreased CRP levels from the lowest to highest UCB quintiles.

Long-Term Outcomes for Chinese COPD Patients After PCI: A Propensity Score Matched, Double-Cohort Study.

ObjectivesThe aim of this study was to analyze long-term outcomes of Chinese coronary artery disease (CAD) patients with (and without) chronic obstructive pulmonary disease (COPD) after percutaneous coronary intervention (PCI).BackgroundChronic obstructive pulmonary disease is a chronic condition which often develops in conjunction with CAD. PCI is a core therapy for CAD, although we still need to understand CAD-COPD outcomes and to identify factors that influence prognoses, across ethnicities.MethodsThis double-cohort study involved 12,343 Chinese CAD patients who received PCI. Baseline characteristics were collected in two independent, specialty centers. Propensity-score matching was performed to control confounding factors, using a nearest neighbor matching method within a 0.02 caliper and on a propensity score scale of 0.1 for each center. Comorbid CAD-COPD cases were compared to non-COPD patients in terms of major adverse cardiac events (MACEs).ResultsPatients with COPD were generally older than those without COPD (65.4 ± 9.2 vs. 58.2 ± 10.3, p < 0.001). There were no significant differences in the end points between COPD and non-COPD groups after PCI (All p > 0.05); however, the incidence of MACEs increased after 450 days. Further subgroup analysis suggests that COPD is approximately four times more prevalent among those aged over 75 years (HR, 3.818; 95%CI, 1.10–13.29; p = 0.027) and those aged below 55 years (HR = 4.254; 95% CI, 1.55–11.72; p = 0.003).ConclusionHaving COPD does not appear to have a significant impact on CAD outcomes 2 years after PCI, and beyond. However, an increasing number of MACEs was observed after 450 days, which suggests that there may be a double-stage effect of COPD on PCI prognosis. There is a need for focused comorbidity management, specifically for those aged below 55 years and above 75 years.

Retrospective analysis of exercise capacity in patients with coronary artery disease after percutaneous coronary intervention or coronary artery bypass graft

ObjectivesTo describe the current state of exercise capacity as well as to identify its predictors in patients with coronary artery disease (CAD) following percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in the mainland of China. MethodsA retrospective study design was employed. We evaluated 230 CAD patients following PCI or CABG in a cardiac rehabilitation center from January 2019 to October 2019. The patients were referred to undergo incremental cardiopulmonary exercise testing with a cycle ergometer. The Zung Self-Rating Anxiety Scale and the Zung Self-Rating Depression Scale were used to evaluate patients’ mental health. Statistical analysis was performed using the chi-square test, Fisher’s exact test, t-test, Mann-Whitney U test, and binary logistic regression. ResultsAmong the 230 patients, 223 patients demonstrated reduced exercise capacity. Resutlts of the logistic regression analysis showed that anxiety (OR = 1.13, 95% CI 1.01–1.32, P = 0.029) was an independent risk factor for reduced exercise capacity in patients following the PCI or CABG. ConclusionsExercise capacity of Chinese CAD patients after PCI or CABG was relatively poor. Alleviating symptoms of anxiety and making exercise prescriptions according to the results of the cardiopulmonary exercise test should be considered during the intervention to improve CAD patients’ exercise capacity.

Association of Epicardial Fat Volume With Increased Risk of Obstructive Coronary Artery Disease in Chinese Patients With Suspected Coronary Artery Disease.

BackgroundEpicardial adipose tissue may be associated with the pathogenesis of coronary artery disease (CAD), but its effect on obstructive CAD risk is uncertain. Therefore, we aimed to examine the relationship between epicardial adipose tissue and obstructive CAD in Chinese patients with suspected CAD.Methods and ResultsThe present study enrolled 194 consecutive inpatients with suspected CAD who underwent both noncontrast computed tomography and coronary angiography. We measured epicardial fat volume (EFV) and evaluated its association with obstructive CAD, which was defined as coronary stenosis severity ≥70%. Overall, 44.3% patients had obstructive CAD and tend to have higher EFV. Age, body mass index, triglycerides, incidence of hypertension, and hyperlipidemia were higher across tertiles of EFV (P for trend <0.05). In univariate regression analysis, a per‐SD increase in EFV was independently associated with obstructive CAD (odds ratio [OR], 2.31; 95% CI, 1.61–3.32; P<0.001). Consistent with these findings, EFV was still significantly related to obstructive CAD as continuous variable after adjustment for all traditional risk factors and coronary artery calcium (OR per SD, 2.82; 95% CI, 1.68–4.74; P<0.001). Generalized additive model indicated that EFV was linearly associated with risk of obstructive CAD. E‐value analysis suggested robustness to unmeasured confounding.ConclusionsOur results suggested that in Chinese patients with suspected CAD, EFV was significantly and positively associated with the risk of obstructive CAD, independent of traditional risk factors and coronary artery calcium.

Association of FMO3 rs1736557 polymorphism with clopidogrel response in Chinese patients with coronary artery disease

Dual antiplatelet therapy with aspirin and clopidogrel is commonly used for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention to prevent stent thrombosis and ischemic events. However, some patients show high on-treatment platelet reactivity (HTPR) during clopidogrel therapy. Genetic factors such as loss-of-function variants of CYP2C19 are validated to increase the risk of HTPR. Flavin-containing monooxygenase 3 (FMO3) is reported to be associated with potency of platelet responsiveness and thrombosis. This study aimed to explore the association between FMO3 rs1736557 polymorphism and clopidogrel response. Five hundred twenty-two Chinese CAD patients treated with dual antiplatelet therapy were recruited from Xiangya Hospital. After oral administration of 300mg loading dose (LD) clopidogrel for 12-24h or 75mg daily maintenance dose (MD) clopidogrel for at least 5days, the platelet reaction index (PRI) was determined by vasodilator-stimulated phosphoprotein-phosphorylation assay. FMO3 rs1736557, CYP2C19*2, and CYP2C19*3 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mean PRI value was significantly higher in CYP2C19 poor metabolizers (PMs) and intermediate metabolizers (IMs) than the extensive metabolizers (EMs) (p < 0.001). In addition, FMO3 rs1736557 AA homozygotes showed significantly lower PRI as compared with carriers of the major rs1736557 G allele in the entire cohort and in the MD cohort (p = 0.011, p = 0.008, respectively). The risk of HTPR was decreased significantly in carriers of the rs1736557 A allele (AA vs GG: OR = 0.316, 95% CI: 0.137-0.726, p = 0.005; AA vs GA: OR = 0.249, 95% CI: 0.104-0.597, p = 0.001; AA vs GG+GA: OR = 0.294, 95% CI: 0.129-0.669, p = 0.002), and the association was observed mainly in patients carrying the CYP2C19 LOF allele and in those administered with MD. The FMO3 rs1736557 AA genotype was related to an increased the antiplatelet potency of clopidogrel in Chinese CAD patients. Additional studies are required to verify this finding.

Prediction of Changes in Adherence to Secondary Prevention Among Patients With Coronary Artery Disease.

Healthcare providers are concerned about adherence to provider recommendations in coronary artery disease management. Seeking patient-related factors influencing changes in adherence over time is necessary for formulating suitable intervention measures-especially among diverse populations. To explore whether health literacy, self-efficacy, and disease knowledge predict changes in adherence over time (between baseline and 3 months) to secondary prevention recommendations for Chinese coronary artery disease patients. A longitudinal study was performed for 662 patients following percutaneous coronary intervention in China. Self-reported data were collected at baseline during hospitalization and at a 3-month telephone follow-up. Variables included demographics, health literacy, self-efficacy, disease knowledge, and adherence to secondary prevention recommendations for medication taking and a heart-healthy lifestyle. Multinomial logistic regression identified predictors of adherence changes over time. Patients were categorized into three groups: sustained/declined to nonadherence between baseline and 3 months, improved to adherence, and sustained adherence. The number of patients in sustained/declined to nonadherence group was small. Absence of stents predicted sustained/declined to nonadherence to medication and lifestyle over time. Health literacy was not associated with adherence changes over time. Higher self-efficacy scores were associated with lower likelihood of sustained/declined to nonadherence to a healthy lifestyle over time, whereas higher disease knowledge scores were associated with higher sustained/declined to nonadherence to medication. Adherence to secondary prevention 3 months after discharge was relatively good in Chinese patients with coronary artery disease who received percutaneous coronary intervention. Absence of stents and lower self-efficacy can predict the poor adherence changes, which should be considered in formulating follow-up care.

Association of leptin and leptin receptor polymorphisms with coronary artery disease in a North Chinese Han population.

INTRODUCTION: Leptin (LEP) is a peptide hormone that acts via leptin receptor (LEPR) binding. Genetic evidence from different human populations has implicated LEP/LEPR in the pathogenesis of coronary artery disease (CAD), and suggests that certain LEP/LEPR gene polymorphisms may increase the risk of CAD. The aim of this study was to assess two single nucleotide polymorphisms (SNPs) in LEP genes (rs2167270 and rs7799039) and two in LEPR genes (rs6588147, rs1137100) for association with CAD.METHODS: We enrolled 271 North Chinese Han CAD patients, and 113 healthy age- and sex-matched controls. Genomic DNA was extracted from whole blood, and the four SNPs were assessed using a MassArray system.RESULTS: The G allele frequency at rs2167270 was significantly higher among CAD cases than among controls. The AG genotype at rs7799039 was associated with a significantly decreased risk of CAD unlike the AA genotype used as the reference. The A allele was significantly associated with the CAD patient group. Interestingly, statistically significant differences in genotype and allele frequency at LEP rs2167270 and rs7799039 existed among females but not among males. CONCLUSIONS: The current study detected a significant association between genetic variations at LEP rs7799039 and rs2167270 and the risk of CAD in a north Chinese population, and revealed that LEP rs2167270 and rs7799039 gene polymorphisms might act as predisposing factors for CAD.

Predictors of adherence to home-based cardiac rehabilitation program among coronary artery disease outpatients in China.

BackgroundCardiac rehabilitation (CR) has proven beneficial for patients with coronary artery disease. However, adherence to CR programs is the key to the health improvement in those patients. Identifying predictors for adherence, which is very much unknown in China, would be valuable for effective rehabilitation. This study aims to determine the adherence to home-based CR programs in Chinese coronary artery disease patients and determine predictors of adherence.MethodsThe current study included 1033 outpatients with coronary heart disease in the First Medical Center of Chinese PLA General Hospital in Beijing from July 2015 to June 2017. Participants were given an exercise prescription and took part in home-based exercise training lasting for 3–24 months. A questionnaire was used to evaluate the completion of the CR program, understanding of the program, motivation of the patients, and family/peer support.ResultsTwo thirds of the patients adhered well to the home-based CR program. Elder patients (≥ 65-year-old) adhere to the program better, while men adhered better than women. Patients who used to exercise (B = 6.756, P < 0.001), understood the program (B = 0.078, P = 0.002), with stronger motivation to participate (B = 0.376, P < 0.001), and received better family support (B = 0.487, P < 0.001) also adhere better to the program.ConclusionsUnderstanding the program, self-motivation of patients, and family support help to keep patients engaged in a home-based CR program. Improvement of family support by educating both patients and families may be helpful in improving adherence to home-based CR programs.

Relationship between drug application and mortality rate in Chinese older coronary artery disease/chronic heart failure patients with and without low glomerular filtration rate

BackgroundThis analysis was designed to investigate the relationship between drug application and mortality rate in Chinese older coronary artery disease (CAD)/chronic heart failure (CHF) patients with and without low glomerular filtration rate (GFR).MethodsAll 1050 Chinese hospitalized patients with diagnosed CAD were included in this analysis, and Cox Regression was used to analyze the relationship between drug application and mortality rate after multivariate adjustment. Low GFR was defined as GFR < 60 ml/min/1.73m2.ResultsThere were 372 patients (35.4%) with low GFR in patients with CAD (1050 patients), and 168 patients (51.4%) in patients with CHF (327 patients). In CAD patients without low GFR, clopidogrel [P = 0.028, odds ratio (OR): 0.620, 95% confidence interval (CI): 0.404–0.951] rather than aspirin (P = 0.173) was significantly associated with lower mortality rate. Statins (P < 0.001, OR: 0.287, 95% CI: 0.180–0.456) were significantly associated with lower mortality rate. In CAD patients with low GFR, aspirin, clopidogrel and statins had no significant relationship with mortality rate (P > 0.05 for all). In CHF patients without low GFR, statins were significantly associated with lower mortality rate (P < 0.001, OR: 0.220, 95% CI: 0.098–0.490). In CHF patients with low GFR, statins had no significant relationship with mortality rate (P > 0.05 for all).ConclusionClopidogrel but not aspirin was beneficial in Chinese older CAD patients without low GFR rather than those with low GFR, and statins benefited for Chinese older CAD/CHF patients without low GFR rather than those with low GFR. These discoveries might offer some help for the therapy of Chinese older patients with cardiovascular/renal diseases.

Association between serum visfatin levels and atherosclerotic plaque in patients with type 2 diabetes

BackgroundVisfatin is a multifaceted protein that plays an important role in regulating a variety of physiological and pathological processes, including obesity, diabetes and cardiovascular disease. However, circulating visfatin levels in atherosclerosis plaque progression in patients with type 2 diabetes, or its association with the vascular territory affected remain unclear.MethodsWe evaluated the relationship between visfatin levels and carotid or femoral artery atherosclerosis in Chinese patients with type 2 diabetes. Serum levels of visfatin were measured by enzyme-linked immunosorbent assay (ELISA) in 97 inpatients with type 2 diabetes. Carotid and/or femoral atherosclerotic plaques were detected by B-mode ultrasound.ResultsSerum visfatin levels were elevated in the group with atherosclerotic plaques compared to the control group without plaques [0.68 (0.46–1.58) versus 0.45 (0.23–0.76) ng/mL, respectively, P = 0.0002]. Patients with carotid plaques showed higher visfatin levels than those with or without femoral plaques. Pearson’s correlation analysis showed that serum visfatin levels were positively correlated with waist circumference (r = 0.226, P = 0.029), waist-hip ratio (r = 0.221, P = 0.032), TG (r = 0.222, P = 0.030) and number of plaques (r = 0.275, P = 0.009). Logistic regression analysis showed that a higher serum visfatin level was an independent predictor for the presence of atherosclerotic plaques.ConclusionsIn conclusion, among patients with T2DM, serum visfatin levels were elevated in those with atherosclerotic plaques, especially in patients with carotid atherosclerotic plaques. Serum visfatin may serve as a predictor of atherosclerotic plaques in patients with T2DM.

Association of Toll-like receptor 4 polymorphisms with the risk of coronary artery disease in the ethnic Zhuang population of the Guangxi Province of China

ObjectivesToll-like receptor 4 (TLR4) is known to be involved in the innate immunity and inflammatory responses that plays a crucial role in the pathogenesis of coronary artery disease (CAD). This study aimed to examine the potential relationship of TLR4 polymorphisms and serum TLR4 protein levels and the risk of CAD in the ethnic Zhuang population of China. Methods1171 serum samples were collected from Zhuang patients, including 556 CAD cases (≥50% luminal stenosis of any coronary vessel) and 615 normal healthy controls (subjects with no luminal stenosis in coronary arteries). Detection of TLR4 polymorphisms was by single base extension polymerase chain reaction (Snapshot PCR) and DNA sequencing (rs11536879A/G and rs11536889G/C) gene sequence in all subjects. Serum TLR4 protein concentrations was measured by ELISA. ResultsThere are significant differences in the allele and genotype frequencies of TLR4 gene rs11536889 between Chinese Zhuang CAD patients and controls, especially in the males. Male carriers of rs11536879 andrs11536889 variant alleles show an increased risk of CAD compared to non-carriers. Serum TLR4 protein levels of CAD patients are higher than controls and the levels tended to increase with the number of coronary artery lesions. Serum TLR4 protein levels of CAD patients showed no correlation with rs11536879 and rs11536889 polymorphisms. ConclusionsThe rs11536879 and rs11536889 polymorphisms of TLR4 gene and serum TLR4 protein levels may contribute to the occurrence and development of CAD. However, the rs11536879 and rs11536889 polymorphisms have no significant effects on the expression of serum TLR4 protein in Zhuang patients with CAD.

Serum Metrnl is associated with the presence and severity of coronary artery disease.

Meteorin‐like (Metrnl) is a novel adipokine that is highly expressed in white adipose tissue. Metrnl stimulates energy expenditure and improves glucose tolerance in rodents. However, whether Metrnl plays a role in coronary artery disease (CAD) remains to be elucidated. The present study aimed to investigate the association of serum Metrnl with CAD in Chinese patients. A total of 193 patients with CAD and 156 control subjects were enrolled in this study. Serum Metrnl concentration was measured by enzyme‐linked immunosorbent assay. Anthropometric phenotypes, fasting glucose, serum lipids, and inflammatory cytokines were measured. Serum Metrnl was lower in CAD patients when compared to those controls (132.41 vs 173.17 pg/mL, P < 0.001). Serum Metrnl was negatively correlated with metabolic parameters, including body mass index, total cholesterol, and low‐density lipoprotein cholesterol as well as inflammatory markers including high‐sensitivity C‐reactive protein, IL‐1β, and IL‐11 even after adjustment for potential confounding variables (P < 0.05). In multivariable logistic regression analyses, compared to those in the highest tertile of serum Metrnl levels, subjects in the lowest tertile had the highest risks for CAD (adjusted OR = 2.63, 95% CI = 1.46‐4.27, P = 0.001). After adjustment for potential confounding variables, serum Metrnl was also decreased as the number of stenosed vessels increased (P < 0.001). Furthermore, decreased Metrnl level was negatively correlated with the severity of CAD quantified by the Gensini score. This first case‐control study shows significant associations of serum Metrnl with the presence and severity of CAD, suggesting Metrnl might be a new promising therapeutic target for CAD.

CRISPLD1 rs12115090 polymorphisms alters antiplatelet potency of clopidogrel in coronary artery disease patients in Chinese Han

BackgroundDual antiplatelet therapy (DAPT) with aspirin and clopidogrel is a recommended treatment for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) to reduce the rate of ischemic events and stent thrombosis. However, high on-treatment platelet reactivity (HTPR) during clopidogrel therapy for some patients may lead to outcome failure and occurrence of cardiovascular events. Amounts of studies have proved that genetic factors may contribute to HTPR. In our study, we explored the predictive value of 10 single nucleotide polymorphisms (SNPs) in 8 genes indicated by exome sequencing with clopidogrel efficacy. MethodsTwo hundred and forty-one Han Chinese CAD patients (mean age: 61 ± 10 years) receiving dual antiplatelet therapy were recruited, among which 118 patients administered with 300 mg loading dose (LD) clopidogrel for 12–24 h and 123 subjects administered with 75 mg/day maintain dose (MD) clopidogrel for at least 5 days before discharge. The platelet reaction index (PRI) was determined to reflect clopidogrel response in the patients. Venous blood samples were drawn from all participants to extract genomic DNA. MassARRAY, Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to determine the genotypes of 10 SNPs. ResultsAllelic tests showed significant differences in genotype distribution between HTPR and normal on-treatment platelet reactivity (NTPR) patients for 3 SNPs including CYP2C19 rs4244285 (CYP2C19*2) (co-dominant model: p = 0.003, dominant model: p = 0.004, recessive model: p = 0.012), CRISPLD1 rs12115090 (co-dominant model: p = 0.011, dominant model: p = 0.004), and LTA4H rs11108379 (dominant model: p = 0.041). After adjusting for covariates including clinical characteristics of patients, concomitant medications and complications, we confirmed that carriers of the CYP2C19*2 showed significantly increased risk of HTPR (*2/*2 vs *1/*1: OR = 12.266, 95% CI: 1.336–112.592, p = 0.027; *1/*2 + *2/*2 vs *1/*1: OR = 2.202, 95% CI: 1.083–4.480, p = 0.029). Contrarily, carriers of the CRISPLD1 rs12115090 C allele showed significantly reduced risk of HTPR (CC vs AA: OR = 0.242, 95% CI: 0.078–0.752, p = 0.014; CA + CC vs AA: OR = 0.457, 95% CI: 0.232–0.904, p = 0.024) in Chinese CAD patients. In addition, carriers of the CYP2C19*2 allele showed significantly increased PRI (*1/*2 vs *1/*1: p = 0.008, 2/*2 vs 1/*1: p < 0.001, *2/*2 vs 1/*2: p = 0.011), while patients carrying the rs12115090 C allele showed significantly decreased PRI than the wild-type AA homozygotes (CA vs AA: p = 0.046, CA + CC vs AA: p = 0.023). ConclusionCYP2C19*2 reduced the antiplatelet potency of clopidogrel and increased the risk of HTPR, while CRISPLD1 rs12115090 A>C polymorphism increased the antiplatelet potency of clopidogrel. Genetic tests, especially for CYP2C19*2 are recommended in Han Chinese CAD patients before using of clopidogrel.

Type D Personality, Social Support, and Depression Among Ethnic Chinese Coronary Artery Disease Patients Undergoing a Percutaneous Coronary Intervention: An Exploratory Study.

This study investigated the relationships between Type D personality, depression, and social support among ethnic Chinese coronary artery disease (CAD) patients undergoing percutaneous coronary interventions. Type D personality is associated with CAD, and may increase patients' depression and mortality rate. However, very few studies have explored the relationships between depression and social support among ethnic Chinese Type D CAD patients. A longitudinal, repeated-measures design was used; 105 Taiwanese CAD patients undergoing a percutaneous coronary intervention were recruited between January and December 2015. A demographic questionnaire, Type D Scale, ENRICHD Social Support Inventory, and Patient Health Questionnaire-9 were completed by 102 participants (mean age = 64.42, SD = 13.67 years) at hospitalization, and at the second week and third month after discharge. Data were analyzed using t tests and a generalized estimating equation. Results indicated that 46.7% of participants who had Type D personality had lower social support and higher depression than did the remaining (non-Type D) participants. At two weeks after discharge, the improvement in social support was higher among Type D patients than non-Type D participants; the same was true for depression at two weeks and three months after discharge each. Type D Taiwanese CAD patients showed lower perceived social support and higher depression during hospitalization than did non-Type D participants. Furthermore, the more social support patients received at home, the lower was their depression. Health-care providers should provide continuous mental health care, conduct early screening of mental health issues, and ensure that patients receive sufficient social support to reduce depression.

Occurrence of composite cardiac endpoints with change in resting heart rate among Chinese patients with coronary artery disease: Chinese cohort from the real-world BISO-CAD study

Objective: We evaluated change in resting heart rate (RHR) and its impact on prognosis in Chinese coronary artery disease (CAD) patients treated with bisoprolol, and also assessed drug safety and tolerability.Methods: This phase IV, single arm observational study was a sub-study of the BISO-CAD study conducted across 20 hospitals in China between October 2011 and July 2015 with follow-up at 6, 12 and 18 months after baseline. The primary endpoint was occurrence of composite cardiac events.Results: A total of 663 CAD patients (baseline RHR 75.47 ± 6.62 bpm) were enrolled in the intent-to-treat (ITT) set, and 513 patients were included in the efficacy analysis (EA) set. In the ITT set, the risk and the number of composite cardiac events in patients with mean RHR 69–74 bpm were significantly higher than in the <65 bpm group (ITT: estimate 1.03 ± 0.47, p = .029). The incidence of the composite cardiac endpoint was not affected by continuous mean RHR (p = .5070). RHR significantly decreased from baseline to 18 months, most obviously in the first 6 months (p < .0001). Ejection fraction and fractional shortening significantly improved in both the ITT and EA sets. An average RHR of 69–74 bpm had a significant effect on admission to hospital for acute coronary syndrome in the ITT (estimate 1.10, HR 3.004, p = .0196) and EA (estimate 1.26, HR 3.526, p = .0132) groups. Seven (1.1%) patients reported drug related adverse events.Conclusion: Reduction in RHR with bisoprolol lowered the incidence of composite cardiac events along with an acceptable safety and tolerability profile.

Is there an incremental value to use myocardial perfusion imaging with or without CT attenuation for the diagnosis of coronary artery disease? A study in Chinese patients.

To evaluate whether computed tomography attention correction (CTAC) has incremental diagnostic value for single photon emission tomography (SPET) myocardial perfusion imaging (MPI) for the detection of coronary artery disease (CAD) in Chinese patients. This retrospective study consisted of 181 suspected CAD patients who underwent one-stop SPET examination by MPI combined with a CT scan. Two observers independently evaluated non-attenuation correction (NAC) and CTAC MPI images, and coronary angiography (CAG) results were used as reference standards. The diagnostic efficacies of the two methods were compared. a) In the whole group, the sensitivity, specificity and accuracy for the detection of CAD were found to be 75.7%, 55.1% and 63.5% for NAC images and 52.7%, 86.9% and 72.9% for CTAC images, respectively; the areas under the receiver operating characteristic curves (AUC) were 0.654 and 0.698 (P>0.05). b) The accuracy of CTAC and the AUC were significantly higher than those for NAC in Chinese males. c) The accuracy of CTAC was also significantly increased for the right coronary artery (RCA) territory and in overweight patients (BMI≥24), although differences in the AUC were marginally insignificant. Compared to NAC MPI, CTAC improved SPET MPI specificity but decreased sensitivity, leading to no obvious improvement in overall accuracy for the diagnosis of CAD in Chinese patients. However, CTAC might be of value in the subgroups of males and overweight patients and for the RCA territory. In routine clinical application, the integration of NAC and CTAC findings combined with CAD pre-test probability could improve MPI diagnostic performance.