Browsing by Subject "Cholesterol, HDL"
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Item Cholesterol Efflux Capacity: Biological and Clinical Determinants in a Large Multi-Ethnic Population Study (Dallas Heart Study)(2018-01-23) Akinmolayemi, Oludamilola; Rohatgi, AnandBACKGROUND: Cholesterol efflux capacity characterizes the ability of HDL to accept cholesterol from extrahepatic cells in the periphery to the liver, which is a crucial step in reverse cholesterol transport. Cholesterol efflux capacity has been shown in clinical studies to be inversely correlated with prevalent coronary disease and incidence of cardiovascular events, but it is still unclear what biological and clinical determinants drive cholesterol efflux capacity. OBJECTIVES : To determine the biological and clinical variables that associate with cholesterol efflux capacity measured with two different methods in a large multi-ethnic population study (Dallas Heart Study 2) and how these associations differ by sex, race, history of diabetes, and history of cardiovascular disease. METHODS: Cholesterol efflux capacity was measured in the cohort (DHS-2) using both fluorescence (BODIPY) and radiolabeled methods. Statistical analysis was performed using Jonckheere-Terpstra trend test, Mann-Whitney test, and multivariate linear regression. Two-sided p values <0.05 were considered to indicate statistical significance. RESULTS: A total of 2373 participants were included. The median age was 51 years, 57% were women, 51% were black, 5% had history of CVD, and 17% had history of diabetes. Cholesterol efflux capacity measured by radiolabeled method was significantly higher in women than in men (P<0.001). Blacks had the lowest cholesterol efflux capacity measured by both BODIDY (p=0.010) and radiolabeled (p<0.001) methods. Participants without history of CVD had higher cholesterol efflux capacity measured by radiolabeled method compared to those with history of CVD (p=0.048). In multivariate regression, risk factors and circulating markers explained more of the variance in efflux using radiolabel than the variance in efflux using BODIPY (R2 0.195 vs. 0.099) with some overlapping and some distinct markers. Stratification by history of CVD, history of diabetes, race, and sex categories did not alter the findings. CONCLUSION: Our analysis revealed that biological and clinical variables that associate with cholesterol efflux capacity vary with measurement methods, but further studies with different study population validating these differences are needed. An understanding of these differences will be useful in identifying targets to improve cholesterol efflux capacity.Item Impaired Cholesterol Efflux Capacity May Help Explain Development of Early Coronary Artery Disease in Subjects with Very High HDL-C(2014-02-04) Agarwala, Anandita; Rodrigues, Amrith; Trinidade, Kevin; Risman, Marjorie; Qu, Liming; Cuchel, Marina; Billheimer, Jeffrey; Rader, Daniel J.Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with apparent 'protection' from CAD. A minority of individuals with very high HDL-C levels also develops CAD, a paradoxical phenotype. We hypothesize that such individuals may have HDL with altered structure and/ or function, and compared these individuals (cases) to individuals with very high HDL-C without CAD (controls). We identified 55 subjects with HDL-C above the 90th percentile, early CAD, and no major risk factors for coronary disease. We selected 120 controls without CAD, each matched for race, gender, and HDL-C level. Controls were selected to be the same age or no more than 10 years older than the cases. Studies to assess HDL composition and size distribution, cholesterol efflux capacity, and lecithin-cholesterol acyltransferase (LCAT) activity in cases and controls were conducted. Comparison of HDL particle characteristics between cases and controls demonstrated a significant reduction in HDL phospholipid composition between cases and controls (92 ± 37 mg/dl vs. 109 ± 43 mg/dL, p value 0.0095). The mean plasma total cholesterol efflux capacity was significantly reduced in subjects with elevated HDL-C and CAD as compared to controls (1.96 ± 0.39 % efflux/ 2hr/ 1% plasma vs. 2.11 ± 0.43 % efflux/ 2hr/ 1% plasma, p value 0.040). The reduction became even more significant when looking at mean ABCA1- selective cholesterol efflux between cases and controls 0.60 ± 0.24 % efflux/ 2hr/ 1% plasma vs. 0.71 ± 0.32 % efflux/ 2hr/ 1% plasma, p value 0.033). Furthermore, there was a significant reduction in mean efflux per HDL particle in cases as compared to controls (0.023 ± 0.005 % efflux/ 2hr/ 1% plasma vs. 0.025 ± 0.006 % efflux/ 2hr/ 1% plasma, p value 0.029). No significant difference was observed between cases and controls in HDL particle size or plasma LCAT activity. Reduced cholesterol efflux capacity in cases with elevated HDL-C and CAD may explain the development of early coronary artery disease. This finding reinforces the belief that cholesterol efflux capacity may in fact be a better predictor of the risk of coronary disease then HDL-C levels alone. Furthermore, the reduction in HDL phospholipid in the cases may help account for impaired cholesterol efflux.