Is raising HDL a futile strategy for atheroprotection?

Area of Science:

• Biochemistry
• Cardiovascular Medicine
• Pharmacology

Background:

• The failure of torcetrapib trials casts doubt on raising high-density lipoprotein cholesterol (HDL-C) for cardiovascular disease treatment.
• HDL metabolism is complex, suggesting HDL's functional quality is more critical than its circulating levels.

Purpose of the Study:

• To review the complexity of HDL metabolism.
• To discuss clinical trial data for HDL-raising agents.
• To consider future HDL-based therapeutic strategies.

Main Methods:

• Literature review of HDL metabolism.
• Analysis of clinical trial data for HDL-raising agents.
• Discussion of torcetrapib's trial failures and future therapeutic potentials.

Main Results:

• Torcetrapib's failure highlights the intricate nature of HDL metabolism.
• HDL functionality may be more important than HDL quantity for cardiovascular health.
• Existing HDL-raising strategies require re-evaluation.

Conclusions:

• Future HDL-based therapies should prioritize enhancing HDL functionality.
• Further research into HDL metabolism is crucial for developing effective cardiovascular treatments.
• A shift from quantity-based to quality-based HDL therapeutics is warranted.