HDL Functions-Current Status and Future Perspectives

Area of Science:

• Biochemistry
• Cardiology
• Epidemiology

Background:

• Cardiovascular disease (CVD) remains a primary cause of mortality in Western nations.
• Low high-density lipoprotein cholesterol (HDL-C) is traditionally linked to CVD development.
• Recent studies reveal a U-shaped association between HDL-C and CVD mortality, indicating increased risk at both low and very high HDL-C levels.

Purpose of the Study:

• To review the current understanding of high-density lipoprotein (HDL) functionality.
• To explore the potential of HDL function as a novel biomarker for cardiovascular disease.
• To discuss future perspectives based on basic research and clinical trial findings.

Main Methods:

• Literature review of basic research findings.
• Analysis of clinical trial data on HDL-C-raising therapies.
• Examination of epidemiological studies on HDL-C and CVD mortality.

Main Results:

• HDL-C-raising therapies (nicotinic acids, CETP inhibitors) have largely failed to reduce CVD events.
• The relationship between HDL-C levels and CVD mortality is complex, showing increased risk at extremely high levels.
• Evidence suggests HDL functionality may be a more relevant indicator of cardiovascular risk than HDL-C levels alone.

Conclusions:

• HDL functionality, rather than HDL-C concentration, may represent a more critical factor in cardiovascular health.
• Further research into the clinical utility of HDL functionality is warranted.
• Rethinking HDL's role beyond cholesterol content is crucial for future therapeutic strategies.