[Laboratory assessment of HDL heterogeneity and function]

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Biochemistry

Context:

• Plasma concentrations of HDL cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) are inversely associated with cardiovascular risk.
• The failure of torcetrapib highlights the importance of HDL heterogeneity and function beyond simple HDL-C levels.
• HDL is a heterogeneous particle with various subfractions and functions contributing to cardiovascular protection.

Purpose:

• To review current knowledge on assays for HDL heterogeneity and function.
• To explore the relationship between HDL subfractions/function and cardiovascular disease.
• To discuss the clinical relevance of assessing HDL characteristics.

Summary:

• HDL is highly heterogeneous, with subfractions identifiable by density, size, charge, and protein composition.
• HDL possesses protective functions including cholesterol efflux, reverse cholesterol transport, anti-inflammatory, and nitric oxide-promoting effects.
• Certain HDL subfractions may be superior predictors of cardiovascular risk compared to overall HDL-C concentration.

Impact:

• Robust assays for HDL subfractions and functions are crucial for clinical application.
• Validation of these assays is needed for predicting cardiovascular risk and guiding therapeutic interventions.
• This research is of significant interest to cardiovascular clinicians, investigators, and clinical chemists.