LAUSR

The urokinase system is pivotal in the pathogenesis of atherosclerosis. Therefore, soluble urokinase plasminogen activator receptor (suPAR) concentrations may help in the detection of functionally relevant coronary artery disease (fCAD). To evaluate suPAR as diagnostic marker for fCAD. Among consecutive patients with symptoms suggestive of fCAD, fCAD was adjudicated blinded to suPAR concentrations in two domains: first, diagnosis of fCAD according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, fCAD according to cardiovascular death, non-fatal acute myocardial infarction (AMI) and all-cause death during 2-year follow-up. Among 968 patients, symptoms were adjudicated to be causally related to fCAD in 26% (255/968). SuPAR concentrations were higher in patients with fCAD as compared to those without (3.45 ng/mL versus 3.20 ng/mL, p=0.007), but overall had only low diagnostic accuracy (area under the curve [AUC]: 0.56, 95% CI 0.52–0.60) and were not independent predictors of fCAD after multivariable adjustment. Circulating suPAR concentrations were modestly correlated with high-sensitivity cardiac troponin (hs-cTn) T (Spearman's rho 0.393, p<0.001), NT-proBNP (Spearman's rho 0.327, p<0.001) and age (Spearman's rho 0.364, p<0.001), but only weakly correlated with the extent of coronary atherosclerosis as quantified by perfusion defects (Spearman's rho 0.123, p<0.001). Prognostically, suPAR concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.72, 95% CI 0.62–0.81) and all-cause death (AUC 0.72, 95% CI 0.65–0.79) at 2-years, and remained a significant predictor for all-cause death after multivariable adjustment (p=0.001). SuPAR concentrations did not predict non-fatal AMI. SuPAR is an independent predictor of death, but not helpful in the detection of fCAD. European Union, Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel,