Is high-density lipoprotein a modifiable treatment target or just a biomarker for cardiovascular disease?

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Lipid Metabolism

Background:

• Epidemiological studies consistently show an inverse relationship between high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular risk.
• Despite decades of research, pharmaceutical interventions aimed at increasing HDL-C have yielded disappointing clinical outcomes.

Purpose of the Study:

• To review the established evidence linking HDL-C levels to cardiovascular risk.
• To discuss the implications of recent clinical trial data for cholesteryl ester transfer protein (CETP) inhibitors.

Main Methods:

• Review of epidemiological data supporting the association between HDL-C and cardiovascular risk.
• Analysis of clinical trial results for CETP inhibitors and their impact on cardiovascular outcomes.

Main Results:

• Cholesteryl ester transfer protein inhibitors effectively raise circulating HDL-C levels by altering lipoprotein metabolism.
• Recent large-scale clinical trials of CETP inhibitors have failed to demonstrate a significant clinical benefit in reducing cardiovascular events.

Conclusions:

• While HDL-C is a recognized marker for cardiovascular risk, interventions targeting HDL-C elevation via CETP inhibition have not translated into improved patient outcomes.
• Further research is needed to understand the complex role of HDL-C and to develop effective strategies for cardiovascular risk reduction.