HDL, Atherosclerosis, and Emerging Therapies

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• High-density lipoproteins (HDLs) are associated with cardioprotection.
• HDL particles possess antiatherosclerotic properties, including cholesterol efflux, antioxidant effects, and modulation of vascular inflammation.
• Epidemiological data show a strong association between HDL-C or apoA-I levels and cardiovascular health.

Purpose of the Study:

• To review HDL properties and their cardioprotective effects.
• To discuss emergent HDL therapies in light of current understanding of HDL function and metabolism.
• To explore novel therapeutic avenues and biomarkers of HDL function.

Main Methods:

• Review of existing literature on HDL properties, function, and metabolism.
• Analysis of epidemiological data and Mendelian randomization studies.
• Evaluation of clinical trial data for HDL-raising therapies.

Main Results:

• While HDL particles have beneficial functions, Mendelian randomization data challenge a direct causal link between HDL-C levels and cardiovascular risk.
• Large-scale clinical trials of HDL-C-raising drugs have not demonstrated efficacy in reducing major cardiovascular events.
• Cholesterol mass within HDL particles may be an inadequate biomarker for therapeutic success.

Conclusions:

• The role of HDL-C levels as a biomarker for cardiovascular risk and therapeutic efficacy needs re-evaluation.
• Focus should shift to understanding HDL's functional capacity beyond cholesterol content.
• Novel therapeutic strategies targeting HDL's antiatherogenic functions are crucial for cardiovascular prevention.