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Updated: Jan 22, 2026

High-throughput Nitrobenzoxadiazole-labeled Cholesterol Efflux Assay
Published on: January 7, 2019
HDL (High-Density Lipoprotein) Cholesterol Efflux Capacity Is Associated With Incident Cardiovascular Disease in the
Sanam Ebtehaj1, Eke G Gruppen2,3, Stephan J L Bakker3
1From the Department of Pediatrics (S.E., U.J.F.T.), University of Groningen, University Medical Center Groningen, the Netherlands.
Insights
Cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, predicts future cardiovascular disease (CVD) events in the general population. Lower baseline CEC is linked to increased CVD risk, independent of HDL-C levels.
Area of Science:
- Cardiovascular Science
- Biomarker Discovery
- Lipid Metabolism
Background:
- High-density lipoprotein cholesterol (HDL-C) is a traditional cardiovascular disease (CVD) biomarker.
- Focus is shifting towards HDL functionalities, specifically antiatherogenic properties.
- Limited data exist on the prospective association of HDL function metrics with CVD events.
Purpose of the Study:
- To determine if baseline cholesterol efflux capacity (CEC) is associated with future CVD events in the general population.
- To investigate the predictive value of HDL function beyond HDL-C levels for CVD.
- To assess CEC in relation to established CVD risk factors.
Main Methods:
- Prospective study of 8267 participants from the PREVEND cohort with 12-year follow-up.
- CEC quantified using macrophage foam cells and apolipoprotein B-depleted plasma.
- Cases with new CVD events were matched to controls for age, sex, smoking status, and HDL-C.
Main Results:
- Despite identical HDL-C and apolipoprotein A-I levels, cases had significantly lower baseline CEC than controls (P<0.001).
- CEC correlated positively with HDL-C and apoA-I, and negatively with BMI, hsCRP, and urinary albumin excretion.
- Lower CEC was inversely associated with incident CVD events (OR, 0.73; P<0.001), independent of HDL-C and other covariates.
Conclusions:
- Baseline cholesterol efflux capacity (CEC) is a significant predictor of future cardiovascular events in the general population.
- CEC provides predictive value for CVD events independently of HDL-C and apolipoprotein A-I levels.
- HDL function, specifically CEC, represents a crucial, independent biomarker for cardiovascular risk assessment.
Objective:
Focus is shifting from HDL-C (high-density lipoprotein cholesterol) as predictive biomarker for cardiovascular disease (CVD) towards antiatherogenic HDL functionalities. Still, limited data exist on the prospective association of HDL function metrics with CVD events. The current work aimed to determine, if baseline HDL-C efflux capacity (CEC) is associated with future CVD events in the general population. Approach and Results: We performed a prospective study among participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort (follow-up, 12 years). From the overall n=8592 subjects 325 with previous CVD events were excluded; of the remaining 8267 eligible participants all subjects with new CVD events during follow-up were selected and individually matched to controls for age, sex, smoking status, and HDL-C levels. CEC at baseline was quantified using human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma. Despite identical HDL-C and apoA (apolipoprotein)-I levels between cases (n=351) and controls (n=354) CEC was significantly lower in cases (0.93±0.29 versus 1.01±0.24 arbitrary units; P<0.001). In all subjects combined, CEC correlated positively with HDL-C and apoA-I and negatively with body mass index, hsCRP (high-sensitivity C-reactive protein), and urinary albumin excretion. CEC was inversely associated with incident CVD events, both expressed per quartile and per 1 SD change (odds ratio, 0.73; 95% CI, 0.62-0.86; P<0.001); this association remained significant after adjustments for HDL-C, hsCRP, kidney function, and several other clinical covariates.
Conclusions:
Combined these data demonstrate that in the general population baseline CEC is significantly associated with the future development of CVD events independent of HDL-C and apoA-I plasma levels.
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