HDL Phospholipid and ABCA1-Mediated Cholesterol Efflux Are Reduced in Patients with Very High HDL-C Who Develop Early Coronary Artery Disease

BACKGROUND: 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. OBJECTIVE: We identified a number of individuals with high HDL-C levels who develop CAD, a paradoxical phenotype and hypothesized that such individuals may have HDL with altered structure and function, and compared controls with similarly high HDL-C and no coronary disease. METHODS: 55 subjects with HDL-C above the 90th percentile, early CAD, and no major known risk factors for coronary disease were identified. We selected 120 controls without CAD, each matched for race, gender, and HDL-C level. RESULTS: Comparison of HDL particle characteristics between cases and controls demonstrated a significant reduction in HDL phospholipid composition and cholesterol efflux capacity in cases as compared to controls. CONCLUSION: Reduced cholesterol efflux capacity in cases with elevated HDL-C and CAD may explain the development of early coronary artery disease. Cholesterol efflux capacity may in fact be a better predictor of the risk of coronary disease then HDL-C levels alone. The reduction in HDL phospholipid in the cases may help account for impaired cholesterol efflux.