Beginning to understand high-density lipoproteins

Carlos G Santos-Gallego1, Juan J Badimon1, Robert S Rosenson1

  • 1Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1030, New York, NY 10029, USA.

Insights

High-density lipoproteins (HDL) were thought to protect against cardiovascular disease (CVD). However, recent studies question HDL's benefits, suggesting cholesterol levels aren't reliable indicators of its protective effects.

Area of Science:

  • Cardiovascular Science
  • Lipid Metabolism
  • Translational Medicine

Background:

  • High-density lipoproteins (HDL) are traditionally linked to reduced cardiovascular disease (CVD) risk.
  • Recent genetic studies and clinical trials challenge the established cardioprotective role of HDL.
  • HDL cholesterol levels, commonly used as a surrogate marker, may not accurately reflect HDL's atheroprotective function.

Purpose of the Study:

  • To reconcile the classic understanding of HDL's role in CVD risk with emerging contradictory evidence.
  • To highlight the limitations of using HDL cholesterol as a sole indicator of HDL's beneficial effects.
  • To discuss current and novel therapeutic strategies targeting HDL metabolism.

Main Methods:

  • Review of genetic association studies.
  • Analysis of data from randomized clinical trials.
  • Examination of established and novel biomarkers for HDL function.

Main Results:

  • HDL cholesterol levels do not consistently correlate with atheroprotective properties.
  • The direct causal relationship between HDL levels and CVD risk reduction is questioned by recent data.
  • More refined measures of HDL metabolism are necessary to assess its true impact on CVD.

Conclusions:

  • The widely accepted role of HDL in preventing cardiovascular disease requires re-evaluation.
  • Relying solely on HDL cholesterol levels for assessing cardiovascular risk is insufficient.
  • Future research and therapies should focus on precise indicators of HDL functionality and metabolism.

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