Abstract 387: HDL Structure and Function in Individuals with Extreme High HDL-C Who Have Coronary Artery Disease Compared with Those Without CAD

Abstract

Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD) in epidemiologic studies, and high HDL-C is generally associated with apparent ‘protection’ from CAD. We have been recruiting individuals with high HDL-C for about 15 years, and while most have no CAD, a minority has premature CAD, a paradoxical phenotype. We hypothesize that such individuals may have HDL with altered structure and/ or function, and are systematically comparing these individuals (cases) to older individuals with extreme high HDL-C without CAD (controls) and a healthy control group with normal HDL-C levels. We identified 60 subjects with HDL-C above the 90th percentile, premature CAD, and no other major risk factors for coronary disease. We selected 2 controls per case, each matched for age, race, gender, and HDL level. Demographic information and lipid profile (mean ± SD) of the study groups are shown below. Controls are well matched to the cases. Studies are well underway to assess HDL size distribution by NMR, HDL composition, total and ABCA1-specific cholesterol efflux capacity, lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in cases and controls. We will also compare to a group of healthy controls with normal HDL-C levels. We expect that the findings from this study will provide insight into the etiology of CAD in this paradoxical phenotype.