One aim is to summarize evidence from observational studies and clinical trials evaluating the inverse relationship between high-density lipoprotein and coronary heart disease. Other aims are to explore the mechanisms underlying the reported cardioprotective effects of high-density lipoprotein and to evaluate therapeutic modalities to increase high-density lipoprotein levels and functionality.
In addition to reverse cholesterol transport, recent data suggest that high-density lipoprotein possesses antioxidant, anti-inflammatory and fibrinolytic properties and the inverse relationship between high-density lipoprotein cholesterol and coronary heart disease is most evident with associated elevations in low-density lipoprotein cholesterol and triglyceride. Recent data suggest, however, that even after low-density lipoprotein cholesterol is sufficiently reduced, residual coronary heart disease risk persists with low high-density lipoprotein cholesterol. The excess death rate reported with the high-density lipoprotein cholesterol raising drug torcetrapib appears to have been the result of an off-target effect of the drug, rather than an effect attributable to cholesteryl ester transfer protein inhibition.
Low high-density lipoprotein cholesterol remains an important consideration in coronary heart disease risk assessment, however several issues remain unresolved. They include the extent to which low high-density lipoprotein cholesterol in the absence of other risk factors augments risk, the relationship between high-density lipoprotein functionality and levels of high-density lipoprotein cholesterol and whether and to what extent improving these parameters independently offsets coronary heart disease risk.
Department of Medicine, University of Maryland Medical Center, Baltimore, Maryland, USA
Correspondence to Michael Miller, Department of Medicine, University of Maryland Medical Center, 22 South Greene Street, Room S3 B06, Baltimore, MD 21201, USA Tel: +1 410 328 6299; fax: +1 410 328 4382; e-mail: firstname.lastname@example.org