title: Soluble urokinase plasminogen activator receptor level is an independent predictor of the presence and severity of coronary artery disease and of future adverse events.
abstract: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown.
  
  
  
  We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C-statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR.
  
  
  
  Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eapen
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Pankaj
authors.initials: P
authors.lastname: Manocha
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Nima
authors.initials: N
authors.lastname: Ghasemzadeh
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.) Department of Medicine, Cardiff University, Cardiff, UK (R.S.P.).
authors.forename: Riyaz S
authors.initials: RS
authors.lastname: Patel
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Hatem
authors.initials: H
authors.lastname: Al Kassem
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hammadah
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Ngoc-Anh
authors.initials: NA
authors.lastname: Le
authors.affiliation: Clinical Research Center, Copenhagen University Hospital Copenhagen, Denmark (T.P., C.W.T.).
authors.forename: Tomasz
authors.initials: T
authors.lastname: Pielak
authors.affiliation: Clinical Research Center, Copenhagen University Hospital Copenhagen, Denmark (T.P., C.W.T.).
authors.forename: Christian W
authors.initials: CW
authors.lastname: Thorball
authors.affiliation: Medical School of Athens, Athens, Greece (A.V., D.T.K., S.L.).
authors.forename: Aristea
authors.initials: A
authors.lastname: Velegraki
authors.affiliation: Medical School of Athens, Athens, Greece (A.V., D.T.K., S.L.).
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Kremastinos
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.) Medical School of Athens, Athens, Greece (A.V., D.T.K., S.L.).
authors.forename: Stamatios
authors.initials: S
authors.lastname: Lerakis
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Laurence
authors.initials: L
authors.lastname: Sperling
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D015331:Cohort Studies; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012995:Solubility; D015996:Survival Rate
chemical_list: D018836:Inflammation Mediators; D055293:Receptors, Urokinase Plasminogen Activator
keywords: C‐reactive protein; biomarker; cardiovascular outcomes; coronary heart disease; inflammation