Is raising HDL a futile strategy for atheroprotection?
The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein inhibitor torcetrapib has led to considerable doubt about the value of raising high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These results have underscored the intricacy of HDL metabolism, with functional quality perhaps being a more important consideration than the circulating quantity of HDL. As a result, HDL-based therapeutics that maintain or enhance HDL functionality warrant closer investigation. In this article, we review the complexity of HDL metabolism, discuss clinical-trial data for HDL-raising agents, including possible reasons for the failure of torcetrapib, and consider the potential for future HDL-based therapies.
Joy
Tisha
T
Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5K8.
Hegele
Robert A
RA
D000577:Amides; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D004952:Esters; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010743:Phospholipids / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000627:therapeutic use; D016896:Treatment Outcome
D000577:Amides; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D004952:Esters; D008075:Lipoproteins, HDL; D010743:Phospholipids; D011804:Quinolines; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; C483909:torcetrapib