The potential for CETP inhibition to reduce cardiovascular disease risk.
BACKGROUND
Although reductions in cardiovascular risk can be achieved by lowering low-density lipoprotein cholesterol, treated patients remain at substantial risk. Epidemiological studies have established that higher levels of high-density lipoprotein cholesterol (HDL-C) are strongly associated with reduced cardiovascular risk, and therefore raising levels of HDL-C may be beneficial. The activity of cholesteryl ester transfer protein (CETP) appears to be inversely correlated with HDL-C levels and thus CETP is an attractive target for intervention to raise levels of HDL-C and potentially reduce residual cardiovascular risk.


OBJECTIVE
This paper reviews the evidence for an atheroprotective role of higher levels of HDL-C, the function of CETP in cholesterol metabolism, and the concept of CETP inhibition as a potential new strategy for decreasing cardiovascular risk. An analysis of clinical studies of CETP inhibition was also performed.


METHODS
MEDLINE (1966 to June 2006), EMBASE (1974 to June 2006), and cardiology conference proceedings were searched for clinical trials of CETP inhibition.


RESULTS
Thirteen reports involving vaccine-based and pharmacological inhibition of CETP were found. Modest and inconsistent elevation of HDL-C was observed with vaccine-based therapy, whereas HDL-C elevation with pharmacological inhibitors was greater and more consistent.


CONCLUSIONS
Elevation of HDL-C via CETP inhibition appears to be a potentially promising approach to reduce cardiovascular disease. Preliminary studies suggest benefits of CETP inhibition on serum lipid levels, and ongoing studies should establish the effects on atherosclerosis and cardiovascular events.
Ansell
Benjamin
B
Division of General Internal Medicine/Health Services Research, University of California Los Angeles School of Medicine, Los Angeles, CA 90095, USA.
Hobbs
F D Richard
FD
D050197:Atherosclerosis / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood / Q000502:physiology; D006801:Humans; D011804:Quinolines / Q000627:therapeutic use; D012307:Risk Factors; D014611:Vaccination
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D011804:Quinolines; C483909:torcetrapib; D002784:Cholesterol