Underappreciated opportunities for high-density lipoprotein particles in risk stratification and potential targets of...

Area of Science:

• Cardiovascular Medicine
• Lipidology
• Biomarker Discovery

Background:

• The established inverse relationship between high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) risk has driven therapeutic development.
• Recent clinical trials targeting increased HDL-C have unexpectedly failed to demonstrate improved cardiovascular outcomes, questioning HDL-C's role as a sole therapeutic target.
• HDL functionality is complex and not fully captured by HDL-C alone; alternative measures like apolipoprotein A-I (apoA-I) and HDL particle number (HDL-P) exist.

Purpose of the Study:

• To review evidence supporting high-density lipoprotein particle number (HDL-P) as a superior biomarker for assessing cardiovascular risk.
• To advocate for HDL-P as the primary therapeutic goal for interventions aimed at modulating HDL levels.
• To discuss the differential impact of lipoprotein-altering therapies on various HDL measures (HDL-C, apoA-I, HDL-P).

Main Methods:

• Review of existing clinical trial data and observational studies.
• Comparative analysis of HDL-C, apoA-I, and HDL-P as predictors of coronary heart disease.
• Evaluation of the effects of various lipid-modifying therapies on different HDL metrics.

Main Results:

• High-density lipoprotein particle number (HDL-P) has emerged as a more robust predictor of coronary heart disease risk compared to HDL-C and apoA-I.
• Lipoprotein-altering medications exhibit varied effects across HDL-C, apoA-I, and HDL-P measurements.
• The clinical utility of HDL-C as a surrogate marker for cardiovascular risk reduction is increasingly being questioned.

Conclusions:

• High-density lipoprotein particle number (HDL-P) is a more reliable biomarker for assessing cardiovascular risk associated with HDL.
• Therapeutic strategies aimed at improving cardiovascular outcomes should prioritize increasing HDL-P.
• Future research and clinical practice should consider HDL-P as a key metric in cardiovascular risk assessment and management.