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HDL-C: Helpful, harmful, hopeful, or guilty by association.

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High-density lipoprotein cholesterol (HDL-C) shows a complex, U-shaped link with atherosclerotic cardiovascular disease (ASCVD) risk. Current research questions HDL-C

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Area of Science:

  • Cardiovascular Medicine
  • Biochemistry
  • Lipid Metabolism

Background:

  • High-density lipoproteins (HDL) have historically been considered protective against atherosclerotic cardiovascular disease (ASCVD).
  • The role of HDL cholesterol (HDL-C) in ASCVD risk has evolved from a simple inverse relationship to a more complex understanding.
  • Recent therapeutic strategies targeting HDL functionality have not consistently yielded cardiovascular benefits.

Purpose of the Study:

  • To review the intricate relationship between HDL-C and ASCVD.
  • To explore the shift in perspective from HDL-C quantity to functionality in ASCVD prevention.
  • To discuss emerging evidence on elevated HDL-C and ASCVD risk, and future therapeutic directions.

Main Methods:

  • Literature review of studies investigating HDL-C and ASCVD.
  • Analysis of recent clinical trials on HDL-modifying therapies.
  • Discussion of biochemical functions of HDL and their impact on cardiovascular outcomes.

Main Results:

  • A U-shaped curve characterizes the relationship between HDL-C levels and ASCVD risk.
  • Enhancing HDL particle function has not reliably translated to reduced cardiovascular events.
  • Evidence suggests elevated HDL-C may be associated with increased ASCVD risk in some contexts.

Conclusions:

  • The utility of HDL-C as a direct therapeutic target for ASCVD prevention is increasingly questioned.
  • HDL-C may serve as a biomarker reflecting complex pathological processes rather than a direct causal factor.
  • Future research should focus on understanding the nuanced role of HDL and its associated factors in cardiovascular health.