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Updated: Apr 20, 2026

High-Density Lipoprotein-Specific Phospholipid Efflux Assay
Published on: September 30, 2025
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.
Abstract:
This article reconciles the classic view of high-density lipoproteins (HDL) associated with low risk for cardiovascular disease (CVD) with recent data (genetics studies and randomized clinical trials) casting doubt over the widely accepted beneficial role of HDL regarding CVD risk. Although HDL cholesterol has been used as a surrogate measure to investigate HDL function, the cholesterol content in HDL particles is not an indicator of the atheroprotective properties of HDL. Thus, more precise measures of HDL metabolism are needed to reflect and account for the beneficial effects of HDL particles. Current and emerging therapies targeting HDL are discussed.
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