Dongfang Su

Association between Serum Interleukin-6 Concentration and Mortality in Patients with Coronary Artery Disease

Objectives. To evaluate whether serum interleukin-6 (IL-6) is associated with increased risk of mortality in coronary artery disease (CAD) patients. Methods. We performed a prospective cohort study of 718 CAD patients from the Guangzhou Cardiovascular Disease Cohort (GCDC) study. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 with all-cause and cardiovascular mortality. Results. During the 1663 person-years of followup, the cumulative all-cause mortality and cardiovascular mortality were 6.5% (n = 47) and 3.3% (n = 24), respectively. The mean length of followup was 2.32 ± 0.81 years. In the multivariable analyses, a one-SD increment in log-transformed serum IL-6 was positively associated with an increased risk of all-cause and cardiovascular mortality, with hazard ratios (HR) of 2.93 (95% CI, 2.11–4.08) and 2.04 (95% CI, 1.34–3.68) within the patients combined and 2.98 (95% CI, 2.12–4.18) and 3.10 (95% CI, 1.98–4.85) within males, respectively. Patients in the highest serum IL-6 tertile versus the lowest tertile were at higher risk of all-cause and cardiovascular mortality, with HR of 17.12 (95% CI 3.11–71.76) and 8.68 (95% CI, 1.88–37.51), respectively. Conclusions. In hospitalized patients with CAD, serum IL-6 is significantly associated with all-cause and cardiovascular mortality.

Relationship between lipid profiles and plasma total homocysteine, cysteine and the risk of coronary artery disease in coronary angiographic subjects

BackgroundHomocysteine and cysteine are considered as risk factors of cardiovascular disease. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice model. We aimed therefore to evaluate whether homocysteine and cysteine are associated with lipid parameters, and the joint effects of them on the risk of coronary artery disease (CAD). Plasma total homocysteine (tHcy), cysteine (tCys) and lipid markers were measured in 2058 consecutive coronary artery angiographic patients.ResultsPlasma tHcy but not tCys correlated negatively with ApoA-I (r = -0.153, P < 0.001) and with HDL cholesterol (r = -0.148, P < 0.001), and correlated positively with the risk of CAD (OR: 1.61; 95% confidence interval; 1.26 to 2.05). Combination of high tHcy and high tCys levels was associated with decreased ApoA-I and HDL cholesterol levels, and with increased risk of CAD (OR: 1.696, 95% CI (1.301-2.211)). Furthermore, low HDL cholesterol combined with low tHcy or high tHcy all had increased risk for CAD (OR: 1.254, 95% CI (1.114-1.565); OR: 1.332, 95% CI (1.093-1.624); respectively) whereas high HDL cholesterol counteracted the harmful effect of high tHcy on the risk of CAD. However, only the combination of high tHcy and high ApoA-I had an increased risk for CAD (OR: 1.438, 95% CI (1.170-1.768)).ConclusionsThe association of homocysteine and cysteine, ApoA-I or HDL cholesterol and their joint effects provide new insights on its role on CAD.

Hyperglycemia and Mortality Among Patients With Coronary Artery Disease

OBJECTIVE Known diabetes is an independent predictor for mortality in coronary artery disease (CAD) patients; however, whether other glucose abnormalities are associated with death risk in CAD patients is unclear. The goal of this study was to examine the association between different glucose states and the risks of all-cause and cardiovascular disease (CVD) mortality among CAD patients. RESEARCH DESIGN AND METHODS The study cohort included 1,726 CAD patients who were 40–85 years of age in the Guangdong Coronary Artery Disease Cohort. Cox proportional hazards regression models were used to estimate the association of baseline glucose status with risk of mortality. RESULTS During a median follow-up of 3.1 years, 129 deaths were recorded, 109 of which were due to CVD. The multivariable-adjusted (age; sex; education; marriage; leisure-time physical activity; smoking; alcohol drinking; BMI; systolic blood pressure; total and HDL cholesterol; glomerular filtration rate; type, severity, duration, and treatment of CAD; history of heart failure; and use of antihypertensive, cholesterol-lowering, and antiplatelet drugs) hazard ratios in normoglycemia, impaired glucose regulation (IGR), newly diagnosed diabetes, and known diabetes were 1.00, 1.58 (95% CI 0.90–2.77), 2.41 (1.42–4.11), and 2.29 (1.36–3.84) for all-cause mortality and 1.00, 1.89 (1.01–3.54), 2.74 (1.50–5.01), and 2.73 (1.52–4.91) for CVD mortality. Assessing fasting plasma glucose only, impaired fasting glucose and newly diagnosed and known diabetes were also associated with increased risks of all-cause and CVD mortality compared with normoglycemia. CONCLUSIONS CAD patients with IGR, newly diagnosed diabetes, and known diabetes have increased risk of CVD mortality.

Plasma S-adenosylhomocysteine is associated with the risk of cardiovascular events in patients undergoing coronary angiography: a cohort study

BACKGROUND Although cross-sectional studies have shown that plasma S-adenosylhomocysteine (SAH), the metabolic precursor of homocysteine, is associated with cardiovascular disease, the prospective relation between plasma SAH and cardiovascular disease risk is unknown. OBJECTIVE The aim of this study was to prospectively evaluate the association between plasma SAH and cardiovascular disease risk in coronary angiography patients. DESIGN Baseline plasma SAH and homocysteine concentrations were measured in 1003 patients aged between 21 and 87 y who underwent coronary angiography. Cox proportional hazards models were used to analyze the association between SAH and homocysteine and the risk of cardiovascular events, including fatal cardiovascular diseases, nonfatal myocardial infarction, and stroke. RESULTS During the median follow-up period of 3.0 y, 93 participants developed cardiovascular events (32.7/1000 person-years). The age- and sex-adjusted hazard ratio of cardiovascular events was 3.38 (95% CI: 2.12, 5.39) for each 1-SD increase in the natural log-transformed SAH concentration. The age- and sex-adjusted hazard ratios of cardiovascular events across quartiles of SAH concentrations were 1.0, 2.25, 2.72, and 3.40 (P-trend = 0.007). Further adjustment for other cardiovascular disease risk factors and plasma homocysteine affected the results only slightly. This positive association between SAH and cardiovascular disease risk did not change when participants were stratified by age group, sex, and other baseline covariates. The results among a subset of participants with significant coronary stenosis were similar. CONCLUSION Higher concentrations of plasma SAH are independently associated with an increased risk of cardiovascular events among patients undergoing coronary angiography. This trial was registered at www.chictr.org as ChiCTR-RNRC-08000270.

The association between smoking quantity and hypertension mediated by inflammation in Chinese current smokers.

Objectives: Previous studies indicated that cigarette smokers were more likely to develop hypertension, and both smoking and hypertension were associated with inflammation. Whether inflammation mediates the relationship of them is unclear. This study aims to examine whether inflammation mediates the association between smoking and hypertension. Methods: Nine hundred and eighty-four Chinese current smokers from a community-based chronic diseases survey in Guangzhou and Zhuhai were interviewed about sociodemographics, smoking, chronic conditions, and other health-related variables. Hypertension was defined according to 2007 European Society of Hypertension and European Society of Cardiology (ESH-ESC) Practice Guidelines. Inflammatory markers including C-reactive protein (CRP), interleukin (IL)-6, IL-1&bgr;, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-&agr; (TNF-&agr;), and vascular cell adhesion molecule-1 (VCAM-1) were measured by flow cytometry. Logistic regressions were performed to assess the mediation of inflammation on the relationship between smoking quantity and hypertension. Results: We observed a positive association between smoking quantity and hypertension (P < 0.05). After controlling for potential confounders, daily cigarette consumption was significantly associated with higher level of CRP and VCAM-1 and lower level of TNF-&agr; among six measured inflammatory markers, and the current smokers with hypertension had significantly higher level of MCP-1 and CRP than those smokers who were normotensive. Furthermore, the association between smoking quantity and hypertension was mediated by CRP, which accounted for 58.59% of the estimated causal effect of smoking on hypertension. Conclusion: We have confirmed previous observations that smoking quantity was positively associated with hypertension, and the results of our study suggested that the association between smoking and hypertension was probably mediated by CRP.

Serum levels of monocyte chemoattractant protein-1 and all-cause and cardiovascular mortality among patients with coronary artery disease.

Background Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors. Methods MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk. Results During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method. Conclusions Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.

Serum Lipids, Apolipoproteins, and Mortality among Coronary Artery Disease Patients

The proatherogenic effect of low-density lipoprotein cholesterol (LDL-C) and antiatherogenic effect of high-density lipoprotein cholesterol (HDL-C) have been confirmed in general population. But controversy arises among coronary artery disease (CAD) patients. The goal of this study was to identify the association of different lipid measurements with CAD prognosis. The study cohort included 1916 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of baseline 6 lipid factors and 3 ratios with all-cause and cardiovascular (CVD) mortality. During a median follow-up of 3.1 years, 147 deaths were recorded, 113 of which were due to CVD. When lipid factors were categorized, HDL-C showed a U-shape association with all-cause and CVD mortality after adjustment for major CVD risk factors. Serum LDL-C, apoB, LDL/HDL ratio, and apoB/apoA-I ratio were positively, and apoA-I level was inversely associated with the risk of CVD mortality. After further pairwise comparison of lipid-related risk, LDL/HDL ratio and LDL-C had stronger association with all-cause and CVD mortality than other proatherogenic measurements among Chinese CAD patients.

The opposite associations of long-chain versus very long-chain monounsaturated fatty acids with mortality among patients with coronary artery disease

Objective Epidemiological evidence suggests that different lengths of carbon chains might predict cardiovascular disease (CVD) events differently. However, little data exist concerning the effects of specific types of monounsaturated fatty acids (MUFAs) stratified by chain length. Therefore, the study aimed to explore whether the associations of long-chain MUFAs (LC-MUFAs: 16:1n-7 and 18:1n-9) and very long-chain MUFAs (VLC-MUFAs: 20:1n-9, 22:1n-9 and 24:1n-9) with mortality were different among patients with coronary artery disease (CAD). Methods Erythrocyte membrane fatty acids were measured at baseline in 1320 Chinese patients with CAD (56.2% were newly diagnosed) in the Guangdong Coronary Artery Cohort from 2008 to 2011. Cox proportional hazards models were used to estimate the association of each MUFA with risk of all-cause mortality and CVD mortality. Results During 4229 person-years of follow-up, 104 deaths occurred, 80 of which were due to CVD. There were no statistically significant associations between overall MUFAs and all-cause mortality and CVD mortality. When we stratified MUFAs, comparing with the lowest quartile, multivariable-adjusted HRs in the top quartile of LC-MUFAs were 0.40 (95% CI 0.21 to 0.75) for all-cause mortality and 0.41 (95% CI 0.20 to 0.85) for CVD mortality, whereas multivariable-adjusted HRs in the highest quartile of VLC-MUFAs were 2.72 (95% CI 1.47 to 5.01) for all-cause mortality and 2.58 (95% CI 1.30 to 5.10) for CVD mortality. Conclusions This study showed an inverse association between LC-MUFAs and mortality and a positive association between VLC-MUFAs and mortality among patients with CAD. These findings may help explain some of the reported controversial effects of MUFAs.

Lack of association between four SNPs in the SLC22A3-LPAL2-LPA gene cluster and coronary artery disease in a Chinese Han population: a case control study

BackgroundLipoprotein (a) (Lp [a]) is known being correlated with coronary artery disease (CAD). The SLC22A3-LPAL2-LPA gene cluster, relating with modulating the level of plasma Lp (a), has recently been reported to be associated with CAD in Caucasians. The purpose of this study was to verify whether this finding can be expanded to the Chinese Han population.Methods and ResultsUsing a Chinese Han sample, which consisted of 1012 well-characterized CAD patients and 889 healthy controls, we tested the associations of four SNPs (rs2048327, rs3127599, rs7767084 and rs10755578) in the SLC22A3-LPAL2-LPA gene cluster, and their inferred haplotypes with the risk of CAD. Allelic, genotypic and haplotype association analyses all showed that the gene cluster was not associated with CAD in this Chinese Han sample.ConclusionsWe for the first time explored the association of the four SNPs in the SLC22A3-LPAL2-LPA gene cluster with CAD in a large Chinese Han sample. Nevertheless, this study did not reveal any significant evidence of this gene cluster to increase the risk of CAD in this population.

Body Mass Index, High-Sensitivity C-Reactive Protein and Mortality in Chinese with Coronary Artery Disease

Background To investigate single and joint associations of body mass index (BMI) and serum high-sensitivity C-reactive protein (hsCRP) with death. Methods The study included 1871 coronary artery disease (CAD) patients aged 40–85 year-old recruited from 2008 to 2011. Cox regression models were used to estimate the association of BMI and hsCRP with mortality. The data was analyzed in 2014. Results During 3.1 years follow-up, 141 deaths were recorded, 110 died of cardiovascular disease (CVD). After adjustment of major CVD risk factors, there was a J-shaped association between BMI and all-cause and CVD mortality, and a positive association between hsCRP and mortality. The J-shaped association of BMI with mortality was present among patients who never smoked or with elevated hsCRP (≥3.0 mg/L). Compared with overweight (BMI 24–27.9 kg/m2) patients with normal hsCRP (<3.0 mg/L), obese patients (BMI≥28 kg/m2) with elevated hsCRP had a 3.41-fold risk of all-cause mortality (95% CI 1.49–7.80) and a 3.50-fold risk of CVD mortality (1.40–8.75), lean patients (BMI<24 kg/m2) with elevated hsCRP concentration had a 2.54-fold risk of all-cause mortality (1.36–4.74) and a 2.36-fold risk of CVD mortality (1.19–4.70). Conclusions The association pattern between baseline BMI and mortality changed among different baseline hsCRP concentrations, indicating that low-grade inflammation may be related to BMI and secondary prognosis of CAD.