Related Experiment Video
Updated: Apr 5, 2026

High-Density Lipoprotein-Specific Phospholipid Efflux Assay
Published on: September 30, 2025
High-density lipoprotein cholesterol efflux capacity as a relevant predictor of atherosclerotic coronary disease
Tetsuya Ishikawa1, Makoto Ayaori2, Harumi Uto-Kondo2
1Division of Cardiology, Saitama Cardiovascular Respiratory Center, Kumagaya, Saitama, Japan.
Insights
Cholesterol efflux capacity, a measure of how well cholesterol is removed from cells, is a stronger predictor of coronary artery disease (CAD) than traditional risk factors in Japanese patients. This finding highlights its clinical relevance in assessing CAD risk.
Area of Science:
- Cardiovascular Disease Research
- Lipid Metabolism
- Biomarker Discovery
Background:
- Atherosclerotic coronary artery disease (CAD) remains a leading cause of mortality worldwide.
- Conventional risk factors, including lipid profiles, have limitations in predicting CAD accurately.
- High-density lipoprotein cholesterol (HDL-C) efflux capacity is a functional measure of HDL's role in reverse cholesterol transport.
Purpose of the Study:
- To evaluate the clinical relevance of macrophage cholesterol efflux capacity as a predictor of CAD.
- To compare cholesterol efflux capacity with conventional coronary and lipid risk variables in Japanese patients.
- To assess the predictive value of cholesterol efflux capacity in a real-world clinical setting.
Main Methods:
- Observational study involving 254 patients undergoing coronary angiography or CT.
- Measurement of cholesterol efflux capacity using a J774 macrophage-based assay with radiolabeled cholesterol.
- Propensity score matching and stepwise logistic regression analysis to adjust for confounding variables.
Main Results:
- Cholesterol efflux capacity was significantly impaired in patients with CAD compared to those without (p=0.001).
- This impairment remained significant after propensity score matching (p=0.019).
- Cholesterol efflux capacity emerged as the single independent predictor of CAD (OR: 0.23; p=0.037), outperforming HDL-C and apoA-I.
Conclusions:
- Cholesterol efflux capacity is a clinically relevant predictor of CAD in Japanese daily practice.
- It offers superior predictive value compared to conventional coronary and dyslipidemia-related variables.
- This functional lipid marker holds promise for improved CAD risk assessment.
Background:
We examined the clinical relevance of high-density lipoprotein cholesterol (HDL-C) efflux capacity from macrophage (cholesterol efflux capacity) as a predictor of atherosclerotic coronary artery disease (CAD) in comparison with that of conventional coronary and lipid risk variables in Japanese daily practice.
Methods And Results:
Fasting blood sampling, including 6 routinely measured dyslipidemia-related variables, was performed at the time of coronary angiography (CAG) or multi-slice coronary computed tomography (MSCT) between January 2011 and January 2013. CAD, defined as native coronary atherosclerosis stenosis >50% by CAG or MSCT, was identified in 182 patients (CAD group), but not in 72 patients (non-CAD group). Cholesterol efflux capacity, measured using a cell-based efflux system in (3)[H]-cholesterol-labeled J774 macrophages in apolipoprotein B-depleted plasma, was significantly impaired in the CAD group compared with the non-CAD group (0.86 ± 0.26 vs. 1.02 ± 0.38; p = 0.001). After adjusting 15 patient and dyslipidemia-related variables using a propensity score matching analysis produced 55 patients in each arm, cholesterol efflux capacity in the CAD group remained to be significant compared with the non-CAD group (0.83 ± 0.24 vs. 0.97 ± 0.36; p = 0.019). Stepwise logistic regression analysis using a backward method after the baseline adjustment showed that cholesterol efflux capacity (odds ratio [OR]: 0.23; 95% confidence interval [CI]: 0.056-0.91; p = 0.037) was the single predictor of CAD, while other variables including HDL-C (p = 0.088) and apolipoprotein (apo) A-I (p = 0.681) were removed owing to those insignificance. The area under the receiver operating characteristic curve after the baseline adjustment was 0.67 (95% CI: 0.51-0.73, p = 0.048 by Hosmer-Lemeshow goodness-of-fit statistics).
Conclusions:
The present observational study conducted under daily clinical practice confirmed that cholesterol efflux capacity is a clinically relevant predictor of CAD among the conventional coronary risk factors and dyslipidemia-related variables.
Related Concept Videos
Coronary Artery Disease IV: Preventive Measures
Coronary Artery Disease I: Introduction
Atherosclerosis I: Introduction
Coronary Artery Disease II: Pathophysiology
Atherosclerosis III: Management
Cholesterol: Significance and Regulation
Considering cholesterol and...

