Evolving concepts on benefits and risks associated with therapeutic strategies to raise HDL

To provide an update on high-density lipoprotein (HDL) biology and emerging new HDL-based therapies for athero-thrombosis.

Atherosclerotic cardiovascular disease remains a major public health threat despite a significant decline over the past three decades. Although current medical therapies, specifically low-density lipoprotein lowering with statins, reduce cardiovascular events by about 25-35%, a substantial residual risk remains, leading to a search for additional therapeutic interventions. In this regard, HDL has emerged as one important target because of epidemiologic evidence linking HDL levels inversely to cardiovascular events, known vascular protective actions of HDL and experimental and clinical research supporting athero-protective actions of HDL. However, complexities of HDL composition, particle size, and metabolism have suggested that HDL functionality, and how HDL is increased, may be important determinants of its protective effects.

Thus the possibility that HDL modification could address the residual risk has brought renewed focus on an old HDL-raising drug, niacin, and a number of newer strategies to exploit the vascular benefits of HDL.