HDL-cholesterol in coronary artery disease risk: function or structure?

Óscar Pérez-Méndez1, Héctor González Pacheco2, Carlos Martínez-Sánchez2

  • 1Department of Molecular Biology, National Institute of Cardiology "Ignacio Chávez", Mexico, DF, Mexico.

Insights

High-density lipoprotein (HDL) cholesterol levels do not reliably predict coronary artery disease (CAD) risk. HDL functionality and subclasses, rather than just cholesterol levels, are emerging as better indicators for cardiovascular risk assessment.

Area of Science:

  • Cardiovascular Research
  • Lipid Metabolism
  • Biomarker Discovery

Background:

  • High-density lipoproteins (HDL) show an inverse relationship with coronary artery disease (CAD).
  • HDL-cholesterol is the standard measure, but interventions to raise it haven't consistently reduced CAD risk.
  • Many myocardial infarction patients have normal HDL-cholesterol, and genetic studies question its causal link to CAD risk.

Purpose of the Study:

  • To explore HDL subclasses as a more effective marker for CAD risk assessment.
  • To investigate the relationship between HDL structure, function, and cardiovascular risk.

Main Methods:

  • Review of existing literature on HDL-cholesterol, HDL functionality, and HDL subclasses in relation to CAD and type 2 diabetes mellitus (T2DM).
  • Analysis of factors influencing HDL structure, including inflammation and environmental influences.
  • Consideration of emerging proteomic and lipidomic profiling techniques for HDL analysis.

Main Results:

  • HDL functionality, not just HDL-cholesterol levels, is crucial for assessing CAD risk.
  • Specific HDL subclass patterns (low large HDL, high small HDL) are linked to increased risk of T2DM and CAD.
  • Inflammation and environmental factors impact HDL structure, complicating direct clinical application.

Conclusions:

  • HDL subclasses offer a promising alternative to HDL-cholesterol for evaluating cardiovascular risk.
  • Further prospective studies are needed to validate the clinical utility of HDL subclasses.
  • Proteomic and lipidomic analyses may yield novel HDL-related biomarkers for future clinical use.

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