Cell-free, high-density lipoprotein-specific phospholipid efflux assay predicts incident cardiovascular disease.

Autor: Sato M; Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.; Division of Community and Family Medicine and Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke-City, Tochigi, Japan.; Biochemical Research Laboratory II, Eiken Chemical Co., Ltd., Shimotsuga-gun, Tochigi, Japan., Neufeld EB; Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA., Playford MP; Section of Inflammation and Cardiometabolic Diseases, NHLBI, NIH, Bethesda, Maryland, USA., Lei Y; Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden., Sorokin AV; Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.; Section of Inflammation and Cardiometabolic Diseases, NHLBI, NIH, Bethesda, Maryland, USA., Aponte AM; Proteomics Core Facility, NHLBI, NIH, Bethesda, Maryland, USA., Freeman LA; Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA., Gordon SM; Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington, Kentucky, USA., Dey AK; Section of Inflammation and Cardiometabolic Diseases, NHLBI, NIH, Bethesda, Maryland, USA., Jeiran K; Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA., Hamasaki M; Division of Community and Family Medicine and Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke-City, Tochigi, Japan.; Biochemical Research Laboratory II, Eiken Chemical Co., Ltd., Shimotsuga-gun, Tochigi, Japan., Sampson ML; The NIH Clinical Center and., Shamburek RD; Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA., Tang J; Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA., Chen MY; Laboratory of Cardiovascular CT, NHLBI, NIH, Bethesda, Maryland, USA., Kotani K; Division of Community and Family Medicine and Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke-City, Tochigi, Japan., Anderson JL; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Dullaart RP; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Mehta NN; Section of Inflammation and Cardiometabolic Diseases, NHLBI, NIH, Bethesda, Maryland, USA., Tietge UJ; Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Clinical Chemistry, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden., Remaley AT; Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.; The NIH Clinical Center and.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2023 Sep 15; Vol. 133 (18). Date of Electronic Publication: 2023 Sep 15.
DOI: 10.1172/JCI165370
Abstrakt: BACKGROUNDCellular 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 assay.METHODSWe 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.RESULTSReceiver 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).CONCLUSIONHDL-SPE could serve as a routine clinical assay for improving CVD risk assessment and drug discovery.TRIAL REGISTRATIONClinicalTrials.gov NCT01621594.FUNDINGNHLBI Intramural Research Program, NIH (HL006095-06).
Databáze: MEDLINE