HDL function and composition in atherothrombotic cardiovascular disease with very high HDL-C

Area of Science:

• Cardiovascular Medicine
• Lipid Metabolism
• Biochemistry

Background:

• Emerging evidence suggests a J-shaped relationship between high-density lipoprotein cholesterol (HDL-C) and atherosclerotic cardiovascular disease (ASCVD).
• Very high HDL-C concentrations (>80 mg/dL) are paradoxically associated with increased ASCVD events.
• The composition and functionality of HDL in individuals with very high HDL-C and ASCVD require further investigation.

Purpose of the Study:

• To determine if individuals with very high HDL-C (>80 mg/dL) and ASCVD exhibit altered HDL composition.
• To assess HDL functionality in individuals with very high HDL-C and ASCVD.
• To explore the relationship between HDL characteristics and cardiovascular risk in this population.

Main Methods:

• Investigated HDL profile and functionality in 49 subjects with very high HDL-C (>80 mg/dL), including 23 with ASCVD.
• Assessed plasma atherogenic lipoprotein-cholesterol levels, cholesterol efflux capacity (CEC), antioxidative potential, and oxidative levels.
• Utilized Nuclear Magnetic Resonance (NMR) for HDL particle size analysis and cell-based assays for endothelial proliferation.

Main Results:

• ASCVD patients had lower atherogenic lipoprotein-cholesterol levels but higher basal HDL oxidative levels compared to non-ASCVD individuals.
• ASCVD participants showed reduced CEC and a lower percentage of large HDL particles, with a trend towards more small particles.
• HDL functionality assays revealed attenuated endothelial proliferation in ASCVD patients, particularly with larger HDL particles.

Conclusions:

• HDL functionality and particle distribution provide more clinically relevant insights into cardiovascular risk than HDL-C concentrations alone.
• Altered HDL composition, including increased oxidation and reduced CEC, contributes to cardiovascular risk in individuals with very high HDL-C.
• These findings highlight the importance of assessing HDL quality beyond mere quantity for risk stratification.