HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: the Lipoprotein...

Area of Science:

• Cardiovascular Medicine
• Lipid Metabolism
• Prognostic Biomarkers

Background:

• High-density lipoprotein (HDL) is heterogeneous, and its subclasses' prognostic value in secondary prevention is debated.
• Understanding HDL subclasses is crucial for refining risk assessment in post-myocardial infarction patients.

Purpose of the Study:

• To investigate the association between HDL subclasses (HDL-C, HDL2-C, HDL3-C) and clinical outcomes in patients receiving secondary prevention.
• To determine if HDL subclass analysis offers superior prognostic information compared to total HDL-C.

Main Methods:

• Collaborative analysis of two prospective cohorts (TRIUMPH and IHCS) including 2465 and 2414 patients, respectively.
• Baseline HDL subclassification using vertical-spin density gradient ultracentrifugation.
• Stratification by tertiles of HDL-C, HDL2-C, and HDL3-C, with multivariable-adjusted hazard ratios calculated for mortality and major adverse cardiovascular events.

Main Results:

• No significant associations were found between total HDL-C or HDL2-C levels and adverse clinical outcomes.
• The lowest tertile of HDL3-C was independently associated with a >50% increased risk of mortality (TRIUMPH) and mortality/myocardial infarction (IHCS).
• These associations remained significant after multivariable adjustment in both cohorts.

Conclusions:

• Low levels of HDL3-C, but not HDL2-C or total HDL-C, are independently linked to an elevated risk of major adverse clinical events in secondary prevention.
• Subclassification of HDL-C provides valuable prognostic information beyond total HDL-C levels.
• Targeting HDL3-C may represent a future therapeutic strategy in cardiovascular disease management.