title: Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease.
abstract: BACKGROUND
  Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker released from leukocytes and endothelial cells that has been associated with atherosclerotic cardiovascular disease. We hypothesized that plasma suPAR level is an independent predictor of coronary microvascular function.
  
  
  METHODS
  Coronary blood flow velocity and plasma suPAR levels were evaluated in patients with non-obstructive coronary artery disease. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal average peak blood flow velocity and coronary microvascular dysfunction was defined as CFR ≤ 2.0 in the setting of a fractional flow reserve value of ≥0.75. Plasma suPAR levels were measured using ELISA technique. The association between suPAR and CFR was investigated using univariate and multivariate regression analyses.
  
  
  RESULTS
  In 66 patients, 47% were men, 26% had diabetes, 68% had hypertension and 76% had dyslipidemia. Mean age was 55 ± 12 years and median suPAR level 2.82 (2.08-3.40) ng/mL. Plasma suPAR levels correlated with age (r = 0.31, p = 0.01), body mass index (r = 0.25, p = 0.04) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.33, p = 0.009). While median suPAR level was not significantly different in patients with different cardiovascular risk factors, patients on statin therapy had significantly higher suPAR level (p = 0.03). SuPAR correlated negatively with CFR and, after multivariate adjustment for established cardiovascular risk factors, medications profiles and hs-CRP, suPAR remained an independent predictor of CFR (B = -0.30, p = 0.04), indicating an independent association between suPAR level and coronary microvascular function.
  
  
  CONCLUSIONS
  In this cross-sectional study, plasma suPAR level was an independent predictor of coronary microvascular function. Larger prospective clinical trials are warranted to investigate the prognostic value of this novel biomarker and the role of immune dysregulation in coronary microvascular disease.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Girum
authors.initials: G
authors.lastname: Mekonnen
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Michel T
authors.initials: MT
authors.lastname: Corban
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Olivia Y
authors.initials: OY
authors.lastname: Hung
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Parham
authors.initials: P
authors.lastname: Eshtehardi
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eapen
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Hatem
authors.initials: H
authors.lastname: Al-Kassem
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Emad
authors.initials: E
authors.lastname: Rasoul-Arzrumly
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Bill D
authors.initials: BD
authors.lastname: Gogas
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: McDaniel
authors.affiliation: Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Pielak
authors.affiliation: Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Thorball
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Sperling
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: hsamady@emory.edu.
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood*; D003326:Coronary Circulation; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007107:Immune System; D007249:Inflammation / Q000097:blood; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator
keywords: Coronary microvascular function; Immune dysregulation; Inflammation; suPAR