Eapen, Danny J2; Manocha, Pankaj2; Ghasemzedah, Nima2; Patel, Riyaz S2; Al Kassem, Hatem2; Hammadah, Muhammad2; Veledar, Emir2; Le, Ngoc-Anh2; Pielak, Tomasz3; Thorball, Christian W1; Velegraki, Aristea4; Kremastinos, Dimitrios T4; Lerakis, Stamatios2; Sperling, Laurence2; Quyyumi, Arshed A2
1 Clinical Research Centre, Amager and Hvidovre Hospital, The Capital Region of Denmark2 Emory University School of Medicine3 Clinical Research Center, Copenhagen University Hospital Copenhagen, Denmark (T.P., C.W.T.).4 Medical School of Athens, Athens, Greece (A.V., D.T.K., S.L.).
INTRODUCTION: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.
Journal of the American Heart Association, 2014, Vol 3, Issue 5
Journal Article; Research Support, N.I.H., Extramural