A review attributes the excess deaths seen with torcetrapib to an off-target effect, not to CETP inhibition, while low HDL remains an important risk marker (Curr Opin Endocrinol Diabetes Obes 2008)

Purpose Of Review: 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.

Recent Findings: 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.

Summary: 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.