HDL modification: recent developments and their relevance to atherosclerotic cardiovascular disease

In the last 2 years, significant advances in the understanding of HDL particle structure and the associations between particle structure, function, and atherosclerosis have been made. We will review and provide clinical and epidemiological context to these recent advances.

Several recent studies have analyzed the associations between HDL particle size distribution, number, and particle function and specific environmental, behavioral, and pharmacologic exposures. Detailed phenotyping of HDL-associated protein complements, particularly apolipoproteins, strongly suggests structural subspecies of HDL exist with differential associations with HDL function and ASCVD risk.

The recent data on biological and structural variation in HDL suggests the existence of relatively discrete particle species, which share a similar structure and function. We propose that the classical taxonomy that clusters HDL particles by cholesterol content is incomplete. Detailed phenotyping of HDL subspecies in clinical and epidemiological research may yield insights into new risk markers and biochemical pathways that could provide targets for atherosclerotic cardiovascular disease (ASCVD) therapy and prevention in the future.