CHOLESTEROL EFFLUX CAPACITY AND ITS ASSOCIATION WITH METABOLIC SYNDROME IN A MULTI-ETHNIC POPULATION (DALLAS HEART STUDY): A CROSS-SECTIONAL STUDY

Metabolic syndrome (MetS) is a multi-component risk factor for cardiovascular disease (CVD) and type 2 diabetes. MetS has been found to be associated with increased risk of incident CVD, cardiovascular morbidity and mortality, and prevalence atherosclerosis. Cholesterol efflux capacity (CEC) is a measure of the functional property of high-density lipoprotein cholesterol (HDL-C). In addition, it characterizes the ability of HDL-C to accept cholesterol from extra-hepatic cells in the periphery to the liver and has been shown in clinical studies to be inversely associated with atherosclerosis cardiovascular disease (ASCVD) and incident cardiovascular disease (CVD) . Low HDL-C is one of the components of MetS and it is important to understand how the functionality of HDL captured through CEC is affected in MetS. The aim of this study was to evaluate the association between CEC and MetS in a multi-ethnic population. In addition, the results obtained based on the labeled cholesterol used in the efflux assay were compared for similarities and differences. A cross-sectional study was performed using data obtained from participants at the entry into Dallas Heart Study phase 2 (DHS 2). DHS 2 is a subset of participants from DHS 1, a multiethnic probability-based cohort study of Dallas County residents supplemented by recruitment of participants’ spouses or significant others. Multivariate regression analyses were performed to assess the relationship between CEC and MetS. A total of 2942 participants were included in the study. The mean age was 49.4 years. A total of 40% of the participants were men and 52% were non-Hispanic Black. CEC measured using radiolabeled cholesterol was found to be inversely associated with MetS in the unadjusted model (odds ratio per 1-SD 0.86; 95%CI 0.80 – 0.93; P=0.0002). This finding remained significant after adjusting for demographics, modifiable risk factors, lipids, post menopausal status, and history of cardiovascular disease. CEC measured using fluorescent labeled cholesterol was not significantly associated with MetS in the unadjusted model, but significant after adjusting for lipids (low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol) (adjusted odds ratio per 1-SD 0.82; 95%CI 0.73 – 0.93; P=0.0013). There was an inverse relationship between cholesterol efflux capacity, irrespective of the labeled cholesterol used in the efflux assay, and metabolic syndrome. With the observed association between cholesterol efflux capacity and metabolic syndrome, cholesterol efflux capacity can serve as a marker to predict metabolic syndrome and to understand the functionality of HDL-C in metabolic syndrome, ultimately allowing for early detection and intervention in reducing the risk of cardiovascular disease

Abstract 15297: High-Density Lipoprotein Function Associates With GlycA, a Novel Inflammation Marker, but Does Not Explain the Association Between GlycA and Incident Cardiovascular Events

Background: High-density lipoproteins (HDL) exert anti-atherosclerotic effects via reverse cholesterol transport, yet this process is impaired in the setting of inflammation. GlycA, a novel integrated glycosylation marker of five acute phase reactants, is linked to CV events. We assessed the hypothesis that GlycA is associated with impaired HDL function measures and that the association between GlycA and incident CV events is partially explained by dysfunctional HDL. Methods: Baseline measurements of HDL cholesterol (HDL-C), HDL particle concentration (HDL-P), and cholesterol efflux capacity were obtained from the Dallas Heart Study, a multi-ethnic cohort of 2225 adults without CVD. GlycA was derived from NMR spectral features. The primary end point was first nonfatal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 11.4 years (N=171). Results: Median age was 43 with 56% women and 47% blacks. The correlation between GlycA and hs-CRP was 0.54 (p\u3c0.0001). HDL-P, HDL-C, and cholesterol efflux were inversely associated with GlycA when adjusted for traditional risk factors, hs-CRP, and all HDL measures (standardized beta estimates: -0.10, -0.20, and -0.06, respectively; all p\u3c0.0002). In Cox proportional hazards models adjusted for risk factors, GlycA was directly associated with incident CV events (HR for Q4 vs. Q1: 2.25, 95% CI 1.33 to 3.82). Further adjustment for cholesterol efflux did not attenuate this association (HR for Q4 vs. Q1: 2.13, 95% CI 1.25 to 3.63), while cholesterol efflux remained inversely associated (HR for Q4 vs. Q1: 0.59, 95% CI 0.39 to 0.89) with the primary outcome (Figure). Conclusions: Worsening inflammation as reflected by higher GlycA levels is associated with lower HDL-C, HDL-P, and cholesterol efflux. Cholesterol efflux does not appear to mediate the association between GlycA and incident CV events. Further studies are warranted to investigate the impact of inflammation on HDL function and CV disease. Download figure Footnotes Author Disclosures: K.A. Riggs: None. P.H. Joshi: Consultant/Advisory Board; Modest; Regeneron. A. Khera: None. K. Singh: None. O. Akinmolayemi: None. C.R. Ayers: None. A. Rohatgi: Research Grant; Significant; Merck. Other Research Support; Modest; NIH, AHA. Consultant/Advisory Board; Modest; Merck, CSL Limited, HDL Diagnostics, Cleveland HeartLabs

Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events.

High-density lipoproteins (HDL) exert anti-atherosclerotic effects via reverse cholesterol transport, yet this salutary property is impaired in the setting of inflammation. GlycA, a novel integrated glycosylation marker of five acute phase reactants, is linked to cardiovascular (CV) events. We assessed the hypothesis that GlycA is associated with measures of impaired HDL function and that dysfunctional HDL may contribute to the association between GlycA and incident CV events. Baseline measurements of HDL cholesterol (HDL-C), HDL particle concentration (HDL-P), apoliprotein A1 (Apo A1), cholesterol efflux capacity, GlycA and high-sensitivity C-reactive protein (hs-CRP) were obtained from the Dallas Heart Study, a multi-ethnic cohort of 2643 adults (median 43 years old; 56% women, 50% black) without cardiovascular disease (CVD). GlycA was derived from nuclear magnetic resonance imaging. Participants were followed for first nonfatal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 12.4 years (n = 197). The correlation between GlycA and hs-CRP was 0.58 (p \u3c 0.0001). In multivariate models with HDL-C, GlycA was directly associated with HDL-P and Apo A1 and inversely associated with cholesterol efflux (standardized beta estimates: 0.08, 0.29, -0.06, respectively; all p ≤ 0.0004) GlycA was directly associated with incident CV events (adjusted hazard ratio (HR) for Q4 vs. Q1: 3.33, 95% confidence interval (CI) 1.99, 5.57). Adjustment for cholesterol efflux mildly attenuated this association (HR for Q4 vs. Q1: 3.00, 95% CI 1.75 to 5.13). In a multi-ethnic cohort, worsening inflammation, as reflected by higher GlycA levels, is associated with higher HDL-P and lower cholesterol efflux. Impaired cholesterol efflux likely explains some of the association between GlycA and incident CV events. Further studies are warranted to investigate the impact of inflammation on HDL function and CV disease