Zhongxia Li

Purified Anthocyanin Supplementation Improves Endothelial Function via NO-cGMP Activation in Hypercholesterolemic Individuals

BACKGROUND Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown. METHODS In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8). RESULTS Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs -1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model. CONCLUSIONS Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.

Anti-inflammatory effect of purified dietary anthocyanin in adults with hypercholesterolemia: a randomized controlled trial.

BACKGROUND AND AIM Atherosclerosis is a chronic inflammatory disease and previous studies have demonstrated that anthocyanin inhibits atherosclerosis. In the present study, we explored the effects of anthocyanins on inflammatory cytokines in hypercholesterolemic adults and cell lines. METHODS AND RESULTS A total of 150 subjects with hypercholesterolemia consumed a purified anthocyanin mixture (320 mg/d) or a placebo twice a day for 24 weeks in a randomized, double-blind trial. Anthocyanin consumption significantly decreased the levels of serum high sensitivity C-reactive protein (hsCRP) (-21.6% vs. -2.5%, P = 0.001), soluble vascular cell adhesion molecule-1 (sVCAM-1) (-12.3% vs. 0.4%, P = 0.005) and plasma IL-1β (-12.8% vs. -1.3%, P = 0.019) compared to the placebo. We also found a significant difference in the LDL-cholesterol (-10.4% vs. 0.3%, P = 0.030) and HDL-cholesterol level changes (14.0% vs. -0.9%, P = 0.036) between the two groups. In cell culture assays in vitro, purified anthocyanin mixture, delphinidin-3-Ο-β-glucoside (Dp-3g) and cyanidin-3-Ο-β-glucoside (Cy-3g) inhibited IL-6 and IL-1β-induced CRP production (P < 0.05) in HepG2 cell line and LPS-induced VCAM-1 secretion (P < 0.05) in porcine iliac artery endothelial cell line respectively in a dose-dependent manner. In addition, the reduction of inflammatory cytokines associated with anthocyanin mixture was stronger when compared with the effects of Dp-3g and Cy-3g separately (P < 0.05). CONCLUSIONS Anthocyanin mixture reduced the inflammatory response in hypercholesterolemic subjects. In addition, different anthocyanin compounds were found to have additive or synergistic effects in mediating anti-inflammatory responses in vitro cell culture assays.

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.

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.

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.

Dietary n-3 Polyunsaturated Fatty Acid Intakes Modify the Effect of Genetic Variation in Fatty Acid Desaturase 1 on Coronary Artery Disease

Background Previous studies suggested that dietary fatty acids could affect blood lipids by interacting with genetic variations in fatty acid desaturase 1 (FADS1). However, little is known about their direct effects on coronary artery disease (CAD). The aim of this study was to evaluate whether dietary n-3 long-chain polyunsaturated fatty acids (LCPUFAs) -eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could modulate the effect of FADS1 rs174547 polymorphism on CAD. Methods FADS1 single-nucleotide polymorphisms rs174547 genotypes were measured in 440 CAD patients and 838 healthy controls. Dietary EPA and DHA intakes were assessed with a validated quantitative frequency food questionnaire. The association between FADS1 rs174547 and CAD was estimated using logistic regression under both dominant and additive genetic models. The interactions between rs174547 polymorphism and LCPUFAs were analyzed by using multiple logistic regression and the “genotype × n-3 LCPUFAs” interaction term was included into the model. Results We found that the minor T allele of FADS1 rs174547 increased CAD risk (OR = 1.36, 95%CIs 1.03-1.80), and observed significant interaction between rs174547 and dietary EPA intakes on CAD (P-interaction = 0.028). The T-allele was only associated with higher CAD risk among individuals with lower dietary EPA intakes, but not in those with higher EPA intakes. Similarly, significant interaction was also observed between rs174547 and dietary DHA intakes on CAD (P-interaction = 0.020). Conclusions Dietary n-3 LCPUFA intakes could modulate the association between FADS1 rs174547 polymorphism and CAD. High dietary n-3 LCPUFA intakes could negate the unfavorable effect of genetic variation in FADS1 on CAD in middle-aged and elderly Chinese population.