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The potential for CETP inhibition to reduce cardiovascular disease risk
Benjamin Ansell1, F D Richard Hobbs
1Division of General Internal Medicine/Health Services Research, University of California Los Angeles School of Medicine, Los Angeles, CA 90095, USA.
Insights
Inhibiting cholesteryl ester transfer protein (CETP) may raise high-density lipoprotein cholesterol (HDL-C) levels, potentially reducing cardiovascular risk. Pharmacological CETP inhibition shows promise for increasing HDL-C more consistently than vaccine-based approaches.
Area of Science:
- Cardiology
- Metabolic Research
- Pharmacology
Background:
- Cardiovascular disease (CVD) remains a significant risk despite low-density lipoprotein cholesterol (LDL-C) reduction.
- Higher high-density lipoprotein cholesterol (HDL-C) levels correlate with reduced CVD risk.
- Cholesteryl ester transfer protein (CETP) activity inversely affects HDL-C, making it a therapeutic target.
Purpose of the Study:
- Review evidence for HDL-C's atheroprotective role.
- Examine CETP's function in cholesterol metabolism.
- Evaluate CETP inhibition as a strategy to decrease cardiovascular risk.
Main Methods:
- Searched MEDLINE, EMBASE, and conference proceedings for CETP inhibition clinical trials.
- Included studies from 1966 to June 2006.
- Analyzed both vaccine-based and pharmacological CETP inhibition studies.
Main Results:
- Identified thirteen reports on CETP inhibition (vaccine and pharmacological).
- Vaccine-based CETP inhibition yielded modest, inconsistent HDL-C increases.
- Pharmacological CETP inhibitors demonstrated greater and more consistent HDL-C elevation.
Conclusions:
- CETP inhibition is a promising strategy for increasing HDL-C and potentially reducing cardiovascular disease.
- Preliminary data indicate CETP inhibition benefits serum lipid profiles.
- Further studies are needed to confirm effects on atherosclerosis and clinical cardiovascular events.
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.
Objectives:
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.
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