Abstract
BACKGROUND. Cellular cholesterol efflux capacity (CEC) is a better predictor of cardiovascular disease (CVD) events than HDLcholesterol (HDL-C) but is not suitable as a routine clinical assay. METHODS. We developed an HDL-specific phospholipid efflux (HDL-SPE) assay to assess HDL functionality based on whole plasma HDL apolipoprotein-mediated solubilization of fluorescent phosphatidylethanolamine from artificial lipid donor particles. We first assessed the association of HDL-SPE with prevalent coronary artery disease (CAD): study I included NIH severe-CAD (n = 50) and non-CAD (n = 50) participants, who were frequency matched for sex, BMI, type 2 diabetes mellitus, and smoking; study II included Japanese CAD (n = 70) and non-CAD (n = 154) participants. We also examined the association of HDL-SPE with incident CVD events in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study comparing 340 patients with 340 controls individually matched for age, sex, smoking, and HDL-C levels. RESULTS. Receiver operating characteristic curves revealed stronger associations of HDL-SPE with prevalent CAD. The AUCs in study I were as follows: HDL-SPE, 0.68; apolipoprotein A-I (apoA-I), 0.62; HDL-C, 0.63; and CEC, 0.52. The AUCs in study II were as follows: HDL-SPE, 0.83; apoA-I, 0.64; and HDL-C, 0.53. Also longitudinally, HDL-SPE was significantly associated with incident CVD events independent of traditional risk factors with ORs below 0.2 per SD increment in the PREVEND study (P < 0.001). CONCLUSION. HDL-SPE could serve as a routine clinical assay for improving CVD risk assessment and drug discovery.
| Original language | English |
|---|---|
| Article number | e165370 |
| Journal | Journal of Clinical Investigation |
| Volume | 133 |
| Issue number | 18 |
| DOIs | |
| State | Published - Sep 15 2023 |
Bibliographical note
Publisher Copyright:© 2023, Sato et al.
Funding
This research was supported in part by the Intramural Research Program of the NIH and NHLBI as well as the Swedish Heart-Lung Foundation (grants 20200637 and 20220271, to UJFT) and an ALF Medicin Project Grant by Region Stockholm (grant number FOUI-962738, to UJFT). We thank Christian Combs of the NHLBI Light Microscopy Core, Haifeng He (NIDDK Electron Microscopy Core) and Christopher Bleck and other members of the NHLBI Electron Microscopy Core for help with preparation and imaging of electron microscopy samples. We also thank Yi-Ping Fu at the NHLBI Division of Intramural Research (DIR) Office of the Clinical Director, Office of Biostatistics Research for her help with statistical analyses. We also thank ane Yan and Johanna Aspsäter from the Biostatistics Core at the Karolinska Institutet for confirming the appropriateness and validity of our statistical analyses in the PREVEND study. We also thank the clinical and nursing staff of the NHLBI, NIH for obtaining clinical data, and the patients for the time spent in the Clinical Center. We also thank Yuka Nagatake of Eiken Chemical Co., Ltd. for her help with experiments and Allan Sniderman (McGill University Health Centre) for his insightful comments.
| Funders | Funder number |
|---|---|
| Region Stockholm | FOUI-962738 |
| National Institutes of Health (NIH) | |
| National Heart, Lung, and Blood Institute (NHLBI) | |
| Hjärt-Lungfonden | 20200637, 20220271 |
ASJC Scopus subject areas
- General Medicine
