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Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration.

ABSTRACT: Coronary endothelial dysfunction (ED)-an early marker of atherosclerosis-increases the risk of cardiovascular events.We tested the hypothesis that cholesterol efflux capacity and high-density lipoprotein (HDL) particle concentration predict coronary ED better than HDL-cholesterol (HDL-C).We studied 80 subjects with nonobstructive (<30% stenosis) coronary artery disease. ED was defined as <50% change in coronary blood flow in response to intracoronary infusions of acetylcholine during diagnostic coronary angiography. Cholesterol efflux capacity and HDL particle concentration (HDL-PIMA) were assessed with validated assays. Cholesterol efflux capacity and HDL-PIMA were both strong, inverse predictors of ED (P<0.001 and 0.005, respectively). In contrast, HDL-C and other traditional lipid risk factors did not differ significantly between control and ED subjects. Large HDL particles were markedly decreased in ED subjects (33%; P=0.005). After correction for HDL-C, both efflux capacity and HDL-PIMA remained significant predictors of ED status. HDL-PIMA explained cholesterol efflux capacity more effectively than HDL-C (r=0.54 and 0.36, respectively). The efflux capacities of isolated HDL and serum HDL correlated strongly (r=0.49).Cholesterol efflux capacity and HDL-PIMA are reduced in subjects with coronary ED, independently of HDL-C. Alterations in HDL-PIMA and HDL itself account for a much larger fraction of the variation in cholesterol efflux capacity than does HDL-C. A selective decrease in large HDL particles may contribute to impaired cholesterol efflux capacity in ED subjects. These observations support a role for HDL size, concentration, and function as markers-and perhaps mediators-of coronary atherosclerosis in humans.

SUBMITTER: Monette JS

PROVIDER: S-EPMC4920704 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration.

Monette Jeffrey S JS Hutchins Patrick M PM Ronsein Graziella E GE Wimberger Jake J Irwin Angela D AD Tang Chongren C Sara Jaskanwal D JD Shao Baohai B Vaisar Tomas T Lerman Amir A Heinecke Jay W JW

Circulation research 20160425 1

<h4>Rationale</h4>Coronary endothelial dysfunction (ED)-an early marker of atherosclerosis-increases the risk of cardiovascular events.<h4>Objective</h4>We tested the hypothesis that cholesterol efflux capacity and high-density lipoprotein (HDL) particle concentration predict coronary ED better than HDL-cholesterol (HDL-C).<h4>Methods and results</h4>We studied 80 subjects with nonobstructive (<30% stenosis) coronary artery disease. ED was defined as <50% change in coronary blood flow in respons ...[more]

PMID: 27114438

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Project description:BackgroundPoor cholesterol efflux capacity (CEC) has been proposed to be an independent risk factor for cardiovascular diseases. However, current evidence is inconsistent, especially in rheumatoid arthritis (RA) patients. This meta-analysis aims to identify whether CEC is impaired or altered by drug therapy in RA.MethodsThe PubMed/MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov databases were browsed to identify studies on CEC in RA patients. The searches mainly focused on studies in human subjects that were published before November 14, 2020, without any language restrictions. The effect size was pooled by the standardized mean differences and mean differences (SMD & MD) as well as the corresponding 95% confidence intervals (CIs) in a random or fixed effect model. Heterogeneity across the studies was tested using Cochran's Q test and I2 statistic. Newcastle-Ottawa Scale and the Downs and Black scale (D&B) were applied to evaluate the quality of included studies. The GRADE-system with its 4-grade evidence scale was used to assess the quality of evidence.ResultsA total of 11 eligible articles, including 6 observational and 5 interventional studies, were retrieved. The pooled results showed that in patients with RA, CEC was not significantly different than in healthy controls (SMD: -0.34, 95% CI: - 0.83 to 0.14), whereas the plasma HDL-C levels was significantly lower (MD: -3.91, 95% CI: - 7.15 to - 0.68). Furthermore, in the before-after studies, the CEC of RA patients (SMD: 0.20, 95% CI: 0.02 to 0.37) increased, but the plasma HDL-C levels (MD: 3.63, 95% CI: - 0.13 to 7.39) remained at a comparable quantity after anti-rheumatic treatment comparing with the baseline. In addition, the funnel plot of included studies displayed a lightly asymmetry, while Egger's and Begg's test did not suggest the existence of publication bias. The quality of evidence was rated according to GRADE as moderate to very low.ConclusionThe current meta-analysis demonstrated that HDL-mediated CEC can be improved by the early control of inflammation and anti-rheumatic treatment in RA patients, which is independent of the plasma HDL-C levels. However, the results should be interpreted with caution because of low-quality and limited quantity of evidence. Future randomized controlled trials are needed to determine whether therapeutic strategies to enhance CEC in RA patients have beneficial effects for preventing CVD.

Project description:It is unclear whether high-density lipoprotein (HDL) cholesterol concentration plays a causal role in atherosclerosis. A more important factor may be HDL cholesterol efflux capacity, the ability of HDL to accept cholesterol from macrophages, which is a key step in reverse cholesterol transport. We investigated the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular disease outcomes in a large, multiethnic population cohort.We measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at baseline in 2924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probability-based population sample. The primary end point was atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes. The median follow-up period was 9.4 years.In contrast to HDL cholesterol level, which was associated with multiple traditional risk factors and metabolic variables, cholesterol efflux capacity had minimal association with these factors. Baseline HDL cholesterol level was not associated with cardiovascular events in an adjusted analysis (hazard ratio, 1.08; 95% confidence interval [CI], 0.59 to 1.99). In a fully adjusted model that included traditional risk factors, HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in the highest quartile of cholesterol efflux capacity versus the lowest quartile (hazard ratio, 0.33; 95% CI, 0.19 to 0.55). Adding cholesterol efflux capacity to traditional risk factors was associated with improvement in discrimination and reclassification indexes.Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events in a population-based cohort. (Funded by the Donald W. Reynolds Foundation and others.).

Project description:BackgroundAlthough HDL cholesterol concentrations are strongly and inversely associated with risk of coronary heart disease, interventions that raise HDL cholesterol do not reduce risk of coronary heart disease. HDL cholesterol efflux capacity-a prototypical measure of HDL function-has been associated with coronary heart disease after adjusting for HDL cholesterol, but its effect on incident coronary heart disease risk is uncertain.MethodsWe measured cholesterol efflux capacity and assessed its relation with vascular risk factors and incident coronary heart disease events in a nested case-control sample from the prospective EPIC-Norfolk study of 25 639 individuals aged 40-79 years, assessed in 1993-97 and followed up to 2009. We quantified cholesterol efflux capacity in 1745 patients with incident coronary heart disease and 1749 control participants free of any cardiovascular disorders by use of a validated ex-vivo radiotracer assay that involved incubation of cholesterol-labelled J774 macrophages with apoB-depleted serum from study participants.FindingsCholesterol efflux capacity was positively correlated with HDL cholesterol concentration (r=0·40; p<0·0001) and apoA-I concentration (r=0·22; p<0·0001). It was also inversely correlated with type 2 diabetes (r=-0·18; p<0·0001) and positively correlated with alcohol consumption (r=0·12; p<0·0001). In analyses comparing the top and bottom tertiles, cholesterol efflux capacity was significantly and inversely associated with incident coronary heart disease events, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterol concentration, log-triglycerides, and HDL cholesterol or apoA-I concentrations (odds ratio 0·64, 95% CI 0·51-0·80). After a similar multivariable adjustment the risk of incident coronary heart disease was 0·80 (95% CI 0·70-0·90) for a per-SD change in cholesterol efflux capacity.InterpretationHDL cholesterol efflux capacity might provide an alternative mechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterol concentration to help reduce risk of coronary heart disease.FundingUS National Institutes of Health, UK Medical Research Council, Cancer Research UK.

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Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration.

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Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration.

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