Time to ditch HDL-C as a measure of HDL function?

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• Low high-density lipoprotein cholesterol (HDL-C) is associated with increased atherosclerotic cardiovascular disease (CVD) risk.
• Genetic studies and clinical trials show inconsistent links between HDL-C levels and CVD risk reduction.
• Existing HDL-C metrics may not fully capture the cardioprotective functions of HDL.

Purpose of the Study:

• To highlight the limitations of HDL-C as a sole predictor of CVD risk.
• To introduce cholesterol efflux capacity (CEC) as a superior functional metric for HDL.
• To emphasize the need for new metrics to assess HDL function and its role in cardioprotection.

Main Methods:

• Review of recent epidemiological and clinical studies on HDL cholesterol and CVD.
• Analysis of data comparing HDL-C levels with cholesterol efflux capacity (CEC) as predictors of CVD.
• Examination of the impact of HDL-targeted therapies on HDL function and particle characteristics.

Main Results:

• Cholesterol efflux capacity (CEC) of serum HDL is a more robust predictor of incident and prevalent CVD risk than HDL-C.
• The cardioprotective effects of therapies that increase CEC remain to be definitively established.
• The impact of HDL-targeted therapies on HDL particle size, concentration, and their relationship to CEC and cardioprotection requires further investigation.

Conclusions:

• Clinical focus should shift from HDL-C levels to HDL function, protein composition, and particle size in relation to CVD risk.
• Understanding HDL metabolism and macrophage CEC is crucial for developing novel functional metrics.
• Linking variations in HDL function and size to HDL-targeted therapies is essential for advancing CVD prevention strategies.