Cholesterol Efflux Capacity and Measurement Assays: A Novel Biomarker of High-Density Lipoprotein (HDL) Function

Abstract Biomarkers of high-density lipoprotein (HDL) function may provide better cardiovascular risk discrimination compared to HDL-cholesterol (HDL-C) mass measurements. Cholesterol efflux from macrophages to plasma reflects the first critical step of reverse cholesterol transport (RCT) and is considered one of the key anti-atherosclerotic functions of HDL. Population-based studies in low and high-risk atherosclerotic cardiovascular disease (ASCVD) cohorts have consistently demonstrated an inverse relationship between the cholesterol efflux capacity (CEC) of human plasma and death or major adverse cardiovascular events (MACE) independent of endogenous HDL-C concentration. Despite the importance of CEC as a biomarker of HDL function and a potential surrogate for clinical outcomes, its measurement has not been standardized to a single, reliable, and reproducible assay. The methodologies to measure CEC vary, often making comparisons between studies difficult. In this presentation, we review the pathways of cholesterol efflux, reverse cholesterol transport, and describe the methodology of measuring CEC ex vivo and the findings linking CEC to human disease.