High-density lipoproteins: a consensus statement from the National Lipid Association

Area of Science:

• Cardiovascular Disease Research
• Lipid Metabolism and Atherosclerosis

Background:

• Elevated high-density lipoprotein cholesterol (HDL-C) has historically been associated with reduced cardiovascular disease (CVD) risk.
• The "HDL hypothesis" suggested that increasing HDL-C levels would lower CVD risk, leading to its consideration as a therapeutic target.
• Recent randomized controlled trials have failed to demonstrate a benefit in raising HDL-C for CVD risk reduction.

Purpose of the Study:

• To evaluate the current status of HDL-C as a therapeutic target for cardiovascular disease.
• To review the structure, composition, and function of HDL particles.
• To identify unanswered questions regarding HDL's role in atherosclerotic disease.

Main Methods:

• Convening of a National Lipid Association expert panel.
• Review of existing observational studies, animal studies, and randomized controlled trial data.
• Evaluation of HDL particle biology and clinical significance.

Main Results:

• Low HDL-C levels identify patients at elevated cardiovascular risk.
• Despite potential antiatherogenic roles of HDL, HDL-C is not currently a recommended therapeutic target.
• Risk-stratified atherogenic lipoprotein burden (LDL-C and non-HDL-C) should remain primary therapeutic targets.

Conclusions:

• HDL-C is not a proven therapeutic target for cardiovascular disease prevention at this time.
• Continued rigorous research into HDL biology, function, and the clinical significance of low HDL-C is essential.
• Development of novel drugs targeting HDL particle modulation should continue, exploring structure and function.