Therapies Targeting HDLc Levels and HDL Function

Abstract Epidemiologic studies have shown that high density lipoprotein cholesterol (HDLc) levels are inversely associated with cardiovascular disease risk. This effect is believed to be mediated by several atheroprotective properties of HDL, including the ability to promote the reverse cholesterol transport and reduce vascular inflammation, oxidative stress and thrombosis. Thus, HDLc has been long considered a valid therapeutic target to reduce residual cardiovascular risk. Unfortunately, results obtained from large clinical trials with drugs increasing HDLc levels have been disappointing and have raised doubts on the effectiveness of this approach. With the recognition that HDLc levels may be a poor indicator of HDL atheroprotective potentials, recent strategies for drug development are focusing on enhancing HDL functions rather than HDLc levels per-se . In this chapter we will review established drugs able to raise HDLc levels as well as emerging HDL-targeting therapies currently undergoing preclinical and clinical research.