Cholesterol Efflux Capacity: Biological and Clinical Determinants in a Large Multi-Ethnic Population Study (Dallas Heart Study)

BACKGROUND: 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.