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Abstract
BACKGROUND. Cellular cholesterol efflux capacity (CEC) is a better predictor of cardiovascular disease (CVD) events than HDL- cholesterol (HDL-C) but is not suitable as a routine clinical 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.
Document Type
Article
Publication Date
9-2023
Digital Object Identifier (DOI)
https://doi.org/10.1172/JCI165370
Funding Information
NHLBI Intramural Research Program, NIH (HL006095-06).
Repository Citation
Sato, Masaki; Neufeld, Edward B.; Playford, Martin P.; Lei, Yu; Sorokin, Alexander V.; Aponte, Angel M.; Freeman, Lita A.; Gordon, Scott M.; Dey, Amit K.; Jeiran, Kianoush; Hamasaki, Masato; Sampson, Maureen L.; Shamburek, Robert D.; Tang, Jingrong; Chen, Marcus Y.; Kotani, Kazuhiko; Anderson, Josephine L. C.; Dullaart, Robin P. F.; Mehta, Nehal N.; Tietge, Uwe T. F.; and Remaley, Alan Thomas, "Cell-free, high-density lipoprotein-specific phospholipid efflux assay predicts incident cardiovascular disease" (2023). Saha Cardiovascular Research Center Faculty Publications. 57.
https://uknowledge.uky.edu/cvrc_facpub/57
Notes/Citation Information
© 2023, Sato et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.