High density lipoprotein and cardiovascular diseases

Abstract

Several epidemiological studies have clearly shown that low plasma levels of high density lipoprotein cholesterol (HDL-C) represent a cardiovascular disease (CVD) risk factor. However, it is unclear if there is a causal association between HDL-C concentration and CVD. A recent study published in the Lancet, which performed two Mendelian randomization analyses, showed that increased HDL-C levels were not associated with a decreased risk of myocardial infarction. These findings, together with the termination of the niacin-based AIM-HIGH trial and the discontinuation of cholesteryl ester transfer protein inhibitor dalcetrapib, challenge the concept that raising of plasma HDL-C will uniformly translate into reductions in CVD risk. HDL particles exhibit several anti-atherosclerotic properties, such as anti-inflammatory and anti-oxidative activities and cellular cholesterol efflux activity. Furthermore, HDL particles are very heterogeneous in terms of size, structure, composition and metabolism. HDL functionality may be associated more strongly with CVD risk than the traditional HDL-C levels. More research is needed to assess the association of the structure of HDL particle with its functionality and metabolism.

Keywords: High density lipoprotein, Functionality, Structure, Cardiovascular risk, Niacin, Cholesteryl ester transfer protein inhibitors

Core tip: Epidemiological studies have shown that low plasma levels of high density lipoprotein cholesterol (HDL-C) represent a cardiovascular disease (CVD) risk factor. However, recent studies challenge the concept that an increase of plasma HDL-C will uniformly translate into a reduction in CVD risk. Certain patients with atherosclerosis may have “dysfunctional” HDL despite normal HDL-C levels. Furthermore, HDL-C levels are influenced by dietary patterns, drugs or concomitant diseases. The association of the structure of HDL particle with its functionality and metabolism has not been fully clarified. More research is needed to assess the association of HDL functionality with CVD risk.