This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Forrester, J. S. Articles by Shah, P.K. Search for Related Content PubMed PubMed Citation Articles by Forrester, J. S. Articles by Shah, P.K. Related Collections Cardiovascular Pharmacology Primary prevention Secondary prevention Pathophysiology Type 2 diabetes Lipid and lipoprotein metabolism

(Circulation. 2005;111:1847-1854.)
© 2005 American Heart Association, Inc.

Contemporary Reviews in Cardiovascular Medicine

Increasing High-Density Lipoprotein Cholesterol in Dyslipidemia by Cholesteryl Ester Transfer Protein Inhibition

An Update for Clinicians

James S. Forrester, MD; Rajenda Makkar, MD; P.K. Shah, MD

From the Cardiology Division, Cedars-Sinai Medical Center, Los Angeles, Calif.

Correspondence to James S. Forrester, MD, Burns and Allen Professor, Division of Cardiology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail forrester{at}cshs.org

Received July 9, 2004; revision received August 21, 2004; accepted October 19, 2004.

Reduced HDL cholesterol may be a risk factor comparable in importance to increased LDL cholesterol. Interventions that raise HDL are antiatherosclerotic, presumably through acceleration of reverse cholesterol transport and by antioxidant and antiinflammatory effects. In the hypercholesterolemic rabbit, HDL levels can be increased by >50% by inhibition of cholesteryl ester transfer protein (CETP), a molecule that plays a central role in HDL metabolism. This HDL-raising effect is antiatherosclerotic in moderately severe hyperlipidemia but appears to be ineffective in the presence of severe hypertriglyceridemia. In humans, mutations resulting in CETP inhibition have been associated with both reduced and increased risk of atherosclerosis. Proposed explanations for these apparently disparate observations are that the antiatherosclerotic effect of CETP inhibition varies with either the metabolic milieu or the degree of CETP inhibition. We now have pharmacological inhibitors of CETP that are capable of increasing HDL by as much as 50% to 100% in humans. The importance of this development is that reduced HDL is a risk factor independent of LDL and that these new agents alter HDL by a magnitude comparable to that of statins on LDL. Clinical trials, now beginning, will need to identify the patient subsets in which CETP inhibition may be more or less effective.

Key Words: atherosclerosis • cholesterol • lipids • metabolism • statins

This article has been cited by other articles:

				G. Ferns and V. Keti HDL-cholesterol modulation and its impact on the management of cardiovascular risk Ann Clin Biochem, March 1, 2008; 45(2): 122 - 128. [Abstract] [Full Text] [PDF]

				U. Tchoua, W. D'Souza, N. Mukhamedova, D. Blum, E. Niesor, J. Mizrahi, C. Maugeais, and D. Sviridov The effect of cholesteryl ester transfer protein overexpression and inhibition on reverse cholesterol transport Cardiovasc Res, March 1, 2008; 77(4): 732 - 739. [Abstract] [Full Text] [PDF]

				A. Isaacs, Y. S. Aulchenko, A. Hofman, E. J. G. Sijbrands, F. A. Sayed-Tabatabaei, O. H. Klungel, A.-H. Maitland-van der Zee, B. H. Ch. Stricker, B. A. Oostra, J. C. M. Witteman, et al. Epistatic Effect of Cholesteryl Ester Transfer Protein and Hepatic Lipase on Serum High-Density Lipoprotein Cholesterol Levels J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2680 - 2687. [Abstract] [Full Text] [PDF]

				C. Harder, P. Lau, A. Meng, S. C. Whitman, and R. McPherson Cholesteryl Ester Transfer Protein (CETP) Expression Protects Against Diet Induced Atherosclerosis in SR-BI Deficient Mice Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 858 - 864. [Abstract] [Full Text] [PDF]

				S. Waxman, F. Ishibashi, and J. E. Muller Detection and Treatment of Vulnerable Plaques and Vulnerable Patients: Novel Approaches to Prevention of Coronary Events Circulation, November 28, 2006; 114(22): 2390 - 2411. [Full Text] [PDF]

				R. V. Milani and C. J. Lavie Cholesteryl Ester Transfer Protein Inhibition: The Next Frontier in Combating Coronary Artery Disease? J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1791 - 1792. [Full Text] [PDF]

				P. Paramsothy and R. Knopp Management of dyslipidaemias. Heart, October 1, 2006; 92(10): 1529 - 1534. [Full Text] [PDF]

				J. T. Mallare, A. H. Karabell, P. Velasquez-Mieyer, S. R.S. Stender, and M. L. Christensen Current and Future Treatment of Metabolic Syndrome and Type 2 Diabetes in Children and Adolescents Diabetes Spectr, October 1, 2005; 18(4): 220 - 228. [Abstract] [Full Text] [PDF]

				A. Gauthier, P. Lau, X. Zha, R. Milne, and R. McPherson Cholesteryl Ester Transfer Protein Directly Mediates Selective Uptake of High Density Lipoprotein Cholesteryl Esters by the Liver Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2177 - 2184. [Abstract] [Full Text] [PDF]