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Updated: Apr 15, 2026
High-Density Lipoprotein-Specific Phospholipid Efflux Assay
Published on: September 30, 2025
High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very
Anandita P Agarwala1, Amrith Rodrigues1, Marjorie Risman1
1From the Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Insights
Extremely high HDL-C (high-density lipoprotein cholesterol) with coronary artery disease (CAD) is unusual. This study found reduced HDL phospholipid content and cholesterol efflux capacity in these patients, suggesting impaired HDL function despite high levels.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Biochemistry
Background:
- Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with coronary artery disease (CAD) risk.
- Extremely high HDL-C in the presence of CAD represents an unusual phenotype.
Purpose of the Study:
- To investigate the composition and function of HDL in individuals with very high HDL-C and CAD.
- To compare HDL from cases with CAD and controls with similar HDL-C levels but no CAD.
Main Methods:
- Analysis of HDL composition and assessment of HDL cholesterol efflux capacity.
- Comparison between 55 cases (very high HDL-C, CAD onset ≈ 60 years, no known risk factors) and 120 matched controls (no CAD).
Main Results:
- HDL phospholipid composition was significantly lower in cases (92 ± 37 mg/dL) compared to controls (109 ± 43 mg/dL; P=0.0095).
- HDL cholesterol efflux capacity was significantly reduced in cases (1.96 ± 0.39) versus controls (2.11 ± 0.43; P=0.04).
Conclusions:
- Reduced HDL phospholipid content and cholesterol efflux capacity are associated with the paradoxical development of CAD in individuals with very high HDL-C.
- These findings suggest that altered HDL composition and function may contribute to CAD despite elevated HDL-C levels.
Objective:
Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with reduced risk of CAD. Extremely high HDL-C with CAD is an unusual phenotype, and we hypothesized that the HDL in such individuals may have an altered composition and reduced function when compared with controls with similarly high HDL-C and no CAD.
Approach And Results:
Fifty-five subjects with very high HDL-C (mean, 86 mg/dL) and onset of CAD at the age of ≈ 60 years with no known risk factors for CAD (cases) were identified through systematic recruitment. A total of 120 control subjects without CAD, matched for race, sex, and HDL-C level (controls), were identified. In all subjects, HDL composition was analyzed and HDL cholesterol efflux capacity was assessed. HDL phospholipid composition was significantly lower in cases (92 ± 37 mg/dL) than in controls (109 ± 43 mg/dL; P=0.0095). HDL cholesterol efflux capacity was significantly lower in cases (1.96 ± 0.39) than in controls (2.11 ± 0.43; P=0.04).
Conclusions:
In people with very high HDL-C, reduced HDL phospholipid content and cholesterol efflux capacity are associated with the paradoxical development of CAD.
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