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CETP Inhibition: does the future look promising?

Peter P Toth1

  • 1Director of Preventive Cardiology, Sterling Rock Falls Clinic, IL 61081, USA. peter.toth@srfc.com

Current Cardiology Reports
|September 13, 2011
PubMed

Insights

Inhibiting cholesteryl ester transfer protein (CETP) increases high-density lipoprotein cholesterol (HDL-C) but its effect on coronary artery disease (CAD) risk remains uncertain. Further research is needed to determine if CETP inhibition reduces cardiovascular events.

Area of Science:

  • Cardiovascular Disease Research
  • Lipid Metabolism
  • Pharmacology

Background:

  • Epidemiologic studies show an inverse relationship between high-density lipoprotein cholesterol (HDL-C) and coronary artery disease (CAD) risk.
  • Low HDL-C levels are prevalent and increasing globally, necessitating therapeutic interventions.
  • Cholesteryl ester transfer protein (CETP) plays a role in neutral lipid transfer between lipoproteins.

Purpose of the Study:

  • To explore the therapeutic potential of CETP inhibition for modulating HDL-C levels.
  • To evaluate the complex relationship between CETP function, HDL-C, and cardiovascular risk.
  • To assess the predicted impact of CETP inhibition on atherosclerosis progression and cardiovascular events.

Main Methods:

  • Review of epidemiologic studies and genetic data related to CETP function and CAD risk.
  • Analysis of pharmacologic strategies targeting CETP activity.
  • Consideration of clinical trial outcomes, such as with torcetrapib.

Main Results:

  • CETP inhibition can significantly elevate HDL-C levels.
  • Loss-of-function mutations in CETP are associated with reduced CAD risk.
  • Clinical experience with torcetrapib highlights complexities in predicting outcomes.

Conclusions:

  • CETP inhibition is a controversial approach to increasing HDL-C due to unpredictable cardiovascular outcomes.
  • The relationship between CETP activity, HDL-C levels, and atherosclerosis is complex.
  • Predicting the efficacy of CETP inhibitors in reducing cardiovascular events requires further investigation.

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