Abstract 1695: The Cholesterol Efflux Capacity of Serum Predicts Carotid Intimal-Medial Thickness Independently of HDL-C and Apo A-I Levels
Background: Plasma levels of HDL-C and apo A-I are inversely correlated to coronary heart disease. However, recent studies raise the possibility that HDL functionality, possibly independent of HDL-C and apo A-I levels, is important in atheroprotection. The main mechanism by which HDL is thought to be protective against atherosclerosis is via reverse cholesterol transport, the process by which cholesterol effluxed from peripheral tissues is returned to the liver for excretion.
Methods and Results: We measured the cholesterol efflux capacity of serum in a cohort of adults without cardiovascular disease in whom carotid intimal-medial thickness (IMT) was also measured (n = 265). Cholesterol efflux capacity was measured using a validated in vitro system: the serum HDL fraction from each subject was incubated with c-AMP treated J774 cells to upregulate ABCA1, at a concentration equivalent to 2% serum. Cholesterol efflux capacity was positively correlated to apo A-I after correction for a basic regression model that included age, gender, race, blood pressure and BMI as well as HDL-C levels (p < 0.001). Cholesterol efflux capacity was negatively associated with IMT (r2 = −0.12, p = 0.05) in univariate analysis. This negative association became stronger in multivariate analysis that included the basic control variables and HDL-C (p = 0.008) and remained significant after additionally controlling for apo A-I (p = 0.002).
Conclusion: Cholesterol efflux capacity of serum negatively correlates with carotid IMT independently of HDL-C and apo A-I levels. These data are consistent with the concept that measures of HDL functionality may provide value in predicting cardiovascular risk beyond measures of HDL mass, and suggest that cholesterol efflux capacity may be useful in this capacity.