Gaoqiang Xie

Combination of carotid intima-media thickness and plaque for better predicting risk of ischaemic cardiovascular events

Background Several indices of carotid atherosclerosis have been studied to investigate their associations with the risk of cardiovascular disease. However, the best index of carotid atherosclerosis that predicts the risk of cardiovascular disease remains unclear. Objective To investigate the index that best reflects the relationship between carotid atherosclerosis and subsequent ischaemic cardiovascular disease (ICVD) events. Design An observational longitudinal study with a 5-year follow-up. Participants 1734 Chinese subjects (623 men, 1111 women) aged 43–79 years at baseline. Main outcome measures ICVD events, including coronary heart disease and ischaemic stroke. Results Carotid intima-media thickness (IMT) at baseline was significantly associated with the risk of ICVD among participants without carotid plaque (multivariable adjusted HR=1.59, 95% CI 1.04 to 2.45) but not among those with plaque (HR=1.04, 95% CI 0.78 to 1.39). However, the total area of plaques (HR=1.29, 95% CI 1.08 to 1.55), the number of plaques (HR=1.14, 95% CI 1.02 to 1.27) and the number of segments with plaque (HR=1.45, 95% CI 1.09 to 1.93) were all significantly associated with ICVD in participants with plaque. Thus, carotid IMT and the number of segments with plaque were combined to establish a summary index—the total burden score (TBS) of carotid atherosclerosis—which was shown to improve the prediction of the 5-year risk of ICVD significantly compared with IMT or the number of segments with plaque alone. The c-statistics and net reclassification index showed that TBS improved the risk prediction by increases of 6.0% and 17.1%, respectively, compared with the conventional risk score. Conclusion The TBS could significantly improve the prediction of ICVD risk and should be used in clinical practice and future studies.

Relationship of serum interleukin-10 and its genetic variations with ischemic stroke in a Chinese general population

Background and Purpose Anti-inflammatory cytokine and its genetic variations may play an important role in the process of atherosclerosis. We assessed whether serum interleukin-10 (IL-10) and its genetic variations are associated with ischemic stroke in a Chinese general population. Methods An epidemiological survey on cardiovascular diseases and their risk factors was carried in a general population in Beijing in 2005. Serum IL-10, IL-6, p-selectin, soluble intercellular adhesion molecule-1 and C-reactive protein were analyzed using ELISA kits, while three IL-10 Single Nucleotide Polymorphisms (SNP) (rs1800872, rs1554286 and rs3021094) were genotyped in 1475 participants. Results A high serum IL-10 (top tertile) was significantly associated with ischemic stroke (multivariable adjusted odds ratio (OR) =0.50; 95%CI 0.31-0.81). Rs1800872 (AA vs. AC+CC genotype, OR=1.60; 1.06-2.39), rs1554286(TT vs. CT+CC genotype, OR=1.59; 1.06-2.39), and rs3021094 (CC/CA vs. AA genotype, OR=1.64; 1.04-2.60) were all significantly associated with ischemic stroke even after controlling for age, sex, smoking, systolic blood pressure, total cholesterol, glucose, body mass index and serum IL-10. The SNP score (a summary index of these SNPs) and IL-10 (top tertile) together significantly improved the discriminative power in predicting ischemic stroke by 3.3% (95%CI: 0.2-6.4, p=0.0398) compared to predictions based on conventional risk factors alone. Conclusions The lower serum IL-10 concentration and its selected genetic variations were significantly associated with an increased likelihood of ischemic stroke in this cross-sectional study. Our results suggest that more prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 and its SNPs as new biomarkers to identify a predisposition towards ischemic stroke.

Cross-sectional and longitudinal association of cigarette smoking with carotid atherosclerosis in Chinese adults.

OBJECTIVE To assess the cross-sectional and longitudinal association of cigarette smoking with carotid atherosclerosis in middle-aged and older Chinese adults. METHODS The study population consisted of 1132 residents in Beijing (748 women and 384 men) aged 35 to 64 years. Information on baseline smoking characteristics, including smoking status and pack-years was collected in 1993-1994. The cohort was resurveyed in 2002 and common carotid artery intima-media thickness (CCA-IMT) and carotid plaques were measured by B-mode ultrasound. RESULTS The multivariable-adjusted mean CCA-IMT at resurvey was significantly associated with smoking status at both resurvey and baseline, and was 0.72 mm for consistent current smokers, 0.71 mm for former and inconsistent smokers, and 0.70 mm for consistent never smokers at both surveys, respectively (p-trend<0.01). The multivariable-adjusted odds ratio [OR, 95% confidence interval (CI)] of having carotid plaques was 1.5 (1.0-2.1) for consistent current smokers vs consistent never smokers. In addition, there was a significant dose-response relationship between baseline smoking pack-years and multivariable-adjusted mean CCA-IMT and risk of having carotid plaques at resurvey. CONCLUSION Smoking is associated with carotid atherosclerosis in middle-aged and older Chinese adults both cross-sectionally and longitudinally. Smoking cessation may play a significant role in prevention and control of cardiovascular diseases in China.

Factors explaining the gender disparity in lipid-lowering treatment goal attainment rate in Chinese patients with statin therapy

BackgroundThe lipid-lowering treatment goal attainment rate is lower for women than for men among Chinese patients, but the reasons for this disparity have not been fully explored yet.ObjectivesTo elucidate the potential factors and the significance of their contributions towards the observed discrepancy in lipid-lowering treatment goal attainment rates between Chinese women and men.MethodsWe used data from 1808 patients from 21 tertiary and 6 secondary hospitals in China who received and maintained statin therapy treatment for at least 2 months. Lipid-lowering treatment goal attainment was defined as low-density lipoprotein cholesterol (LDL- C) reaching the treatment targets recommended by the Chinese Guidelines on Prevention and Control of Dyslipidemia in Adults. Logistic Regression was used to explore possible factors associated with gender disparity in goal attainment rates, and to what extent each factor contributes.ResultsA total of 674 women and 1134 men were enrolled in the study. Women had a significantly lower LDL-C goal attainment rate than that of men (46.0% vs 53.8%, P = 0.002), particularly in high and very high CVD risk groups. Among high and very high risk patients, approximately 35%, 7%, 5%, and 5% of gender disparity in LDL-C goal attainment rate was attributable to the gender difference in baseline LDL-C level, cardiovascular co-morbidities and associated risk factors, socioeconomic status, and the dosage of statin treatment, respectively. Approximately 50% of the gender disparity remained unexplained by these factors.ConclusionsAlthough nearly half of the gender disparity in lipid-lowering treatment goal attainment rate can be explained by the gender differences in baseline lipid level, socioeconomic status, cardiovascular co-morbidities and associated risk factors, and the dosage of statin in high and very high CVD risk patients, the other half of the gender disparity remains unexplained and requires further study to fully understand what other factors are at play.

Genome-wide association study on progression of carotid artery intima media thickness over 10 years in a Chinese cohort

BACKGROUND Carotid artery intima media thickness (IMT) in human is a marker of subclinical atherosclerosis with high heritability. Many genome-wide association studies (GWAS) were performed in European and American populations, yet discovery efforts have been limited in Asians. OBJECTIVE To identify the genetic determinants of 10-year progression of IMT using GWA approach in a Chinese cohort. METHODS Cardiovascular epidemiologic survey was carried out in 810 Chinese adults in 2012. 302,218 single-nucleotide polymorphisms (SNP) in whole genome were genotyped using gene chip and carotid IMT was measured. Most of these participants, had previous carotid IMT measurements in 2002 (n = 572), 2005 (n = 750), 2007 (n = 747), and 2010 (n = 671). General linear model (GLM) and multiple linear mixed-model (MLM) were used to assess the association between SNPs and carotid IMT. RESULTS The mean age (SD) of the sample was 61.3 (5.1) years; 33.6% were men. The adjusted GLM showed no SNP with significance association at genome-level (all p > 1 × 10(-7)). However, using MLM, after adjusting for age, sex, number of cigarettes smoked per day, systolic blood pressure, use of antihypertensive drugs in the past 2 weeks, serum cholesterol, body mass index, fasting glucose levels, use of insulin or hypoglycemic drugs, time of measuring IMT and its interaction with SNP, we identified two novel SNPs (rs36071027 in EBF1 gene on chromosome 5 and rs975809 close to PCDH15 gene on chromosome 10) that are significantly associated with carotid IMT at genome level (p < 1 × 10(-7)) and seven novel SNPs (rs2230307 in AGL gene on chromosome 1, rs12040273 in GALNT2 gene on chromosome 1, rs4536103 in NEUROG3 gene on chromosome 10, rs9855415 in LOC647323 gene on chromosome 3, rs2472647 in PCDHGA1 gene on chromosome 5, rs17433780 in GBP3 gene on chromosome 1, and rs7625806 in DLEC1 gene on chromosome 3) which are suggestive of significant association (p < 10(-5)). CONCLUSION The study represents the first GWAS of association between SNPs and carotid IMT in an Asian population. We identified 2 novel loci associated with carotid IMT progression over 10 years.

Relationship between −592A/C polymorphism of interleukin-10 (IL-10) gene and risk of early carotid atherosclerosis

Abstract In a community-based study of 1295 Chinese men and women free of myocardial infarction and stroke we found that interleukin-10 (IL-10) −592C/C genotype was significantly associated with decreased risk of early carotid atherosclerosis compared to −592 A/A genotype. This observed association was significantly modified by known atherogenic risk factors namely smoking and obesity. In people with normal cholesterol (

Baseline Health-Related Quality of Life and 10-Year All-Cause Mortality among 1739 Chinese Adults

Background and Purpose Health-related quality of life (HRQOL) may be associated with the longevity of patients; yet it is not clear whether this association holds in a general population, especially in low- and middle-income countries. The objective of this study was to determine whether baseline HRQOL was associated with 10-year all-cause mortality in a Chinese general population. Methods A prospective cohort study was conducted from 2002 to 2012 on 1739 participants in 11 villages of Beijing. Baseline data on six domains of HRQOL, chronic diseases and cardiovascular risk factors were collected in either 2002 (n = 1290) or 2005 (n = 449). Subjects were followed through the end of the study period, or until they were censored due to death or loss to follow-up, whichever came first. Results A multivariable Cox model estimated that Total HRQOL score (bottom 50% versus top 50%) was associated with a 44% increase in all-cause mortality (Hazard Ratio [HR] = 1.44; 95% confidence interval [CI]: 1.00-2.06), after adjusting for sex, age, education levels, occupation, marital status, smoking status, fruit intake, vegetable intake, physical exercise, hypertension, history of a stroke, myocardial infarction, chronic respiratory disease, and kidney disease. Among the six HRQOL domains, the Independence domain had the largest fully adjusted HR (HR = 1.66; 95% CI: 1.13-2.42), followed by Psychological (HR = 1.47; 95% CI: 1.03-2.09), Environmental (HR = 1.43, 95% CI: 1.003-2.03), Physical (HR = 1.38; 95% CI: 0.97-1.95), General (HR = 1.37; 95% CI: 0.97-1.94), and the Social domain (HR = 1.15; 95% CI: 0.81-1.65). Conclusion Lower HRQOL, especially the inability to live independently, was associated with a significantly increased risk of 10-year all-cause mortality. The inclusion of HRQOL measures in clinical assessment may improve diagnostic accuracy to improve clinical outcomes and better target public health promotions.

The impact of severity of hypertension on association of PGC-1alpha gene with blood pressure and risk of hypertension.

BackgroundLittle is known about the impact of severity of hypertension on the association of genes with high blood pressure, which may cause the inconsistently reported associations of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene with blood pressure.MethodsA cardiovascular epidemiology survey and genotyping were performed in a population-based sample of 1642 apparently healthy residents (648 men and 994 women aged 35–91 years).ResultsAfter adjusting for age, sex, body mass index, and antihypertensive medication, G482S and +2962A/G polymorphisms were significantly associated with systolic blood pressures in hypertension patients with medication use (p = 0.023 and 0.022 for G482S and +2962A/G respectively) but not in all participants, normotensives, and patients with no medication use. Multivariable logistic models showed that the two polymorphisms were significantly associated with severe hypertension (SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg regardless of medication use), with an OR of 0.6(95% confidence interval [CI]: 0.4–0.98) for S482S vs. G482G and an OR of 1.9(95% CI: 1.2–3.0) for +2962G/G vs. +2962A/A, but not with regular hypertension (SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg or current use of antihypertensive medications), with an OR of 0.9(95% CI: 0.7–1.2) for S482S vs. G482G and an OR of 0.9(95% CI: 0.7–1.4) for +2962G/G vs. +2962A/A. Haplotype combination analyses showed a significant synthetic effect (OR of severe hypertension for persons with G482X and +2962G/G = 2.6, 95%CI: 1.5–4.4, with reference to persons with S482S and +2962A/X).ConclusionIn this study, we found that G482S and +2962A/G polymorphisms of PGC-1α gene were only significantly associated with severe hypertension defined by occasional clinic blood pressure measurements. This finding suggested severe hypertension rather than regular hypertension should be used as the outcome in studies on association of genes with blood pressure or hypertension, in order to have a better power.

Factors associated with compliance to lipid-lowering treatment in China:

Background: There are an estimated 200 million people in China with dyslipidaemia. We sought to explore factors that influence compliance to treatment of dyslipidaemia, using a multi-centre sample in China. Methods: Through review of medical notes and direct interviews at two points in time (2006 and 2007) of 2094 patients in 27 hospitals receiving lipid-lowering therapy since 2004, 1890 patients were recruited who had been on treatment for more than one year. Good compliance (GC) was defined as days taking lipid-lowering drugs/total days of follow-up ≥80%. Logistic regression models were used to assess factors associated with GC. Results: In patients with one, two and three years of treatment respectively, GC was greater in those with higher versus lower medical insurance cover – odds ratios 2.8 (95%CI 2.2–3.7), 2.0 (1.5–2.7), 4.3 (2.3–8.1); in patients in province-level versus county-level hospitals–2.0 (1.5–2.6), 2.9 (2.0–4.1), 4.6 (1.8–12.0); in patients treated by non-cardiology physicians compared to cardiologists −1.7 (1.1–2.5), 2.0 (1.3–3.0), 4.0 (1.5–10.3) and in patients using a statin versus other forms of medication for dyslipidaemia −1.7 (1.2–2.2), 1.7 (1.2–2.3), 4.4 (2.3–8.5). Conclusions: Better medical insurance cover, care in a province-level hospital rather than county-level hospital, treatment by a non-cardiologist and use of a statin were associated with better compliance to lipid-lowering treatment.

Prescription of statins at discharge and 1-year risk of major clinical outcomes among acute coronary syndromes patients with extremely low LDL-cholesterol in clinical pathways for acute coronary syndr

The aim of this study was to investigate statin description on discharge and the benefit on the long‐term outcomes in acute coronary syndromes (ACS) patients with very low baseline LDL‐cholesterol (LDL‐c).