Soluble urokinase plasminogen activator receptor (suPAR) can predict long-term mortality in patients with acute chest pain. (25th November 2020) - Chew-Harris, J
Abstract: Background: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory protein associated with plaque instability. Its modulation may reflect on immune dysfunction related to cardiovascular disease burden. We describe the prognostic performance of suPAR in patients presenting with chest pain suspicious of acute myocardial infarction (AMI). Methods: suPAR concentrations were measured at presentation using the ViroGates CE-marked ELISA in 812 patients with the primary complaint of acute chest pain. Standard cardiac markers including hsTnT and NT-proBNP (both Roche) were also measured. Data for all biomarkers were treated as continuous and expressed as median [interquartile range (IQR)]. Statistical assessment was made using SPSS v25 (IBM). Groups were compared by Mann-Whitney U test/Spearman's rho. Prognostic performance of suPAR was assessed using receiver operator curve (ROC) area under the curve (AUC), Cox-proportional hazards regression and Kaplan-Meier analyses. Results: In this chest pain cohort [median age: 63 yrs (IQR: 54–74), 34% female], 156/812 of patients had adjudicated AMI [STEMI (n=22)/NSTEMI (n=134)]. Total all-cause mortality was 18% within 10 yrs. Although median suPAR concentrations were elevated in AMI patients versus all other diagnoses [3.2 ng/mL (IQR:2.4–4.3) vs 2.7 ng/mL (IQR:2.2–3.6) (P<0.0001)], it did not assist in AMI diagnosis (ROC-AUC=0.60). In the entire chest pain cohort, suPAR (AUC≥0.82) had comparable discrimination to that of NT-proBNP (AUC≥0.84) for the prediction of mortality within 2 yrs (n=52), 4 yrs (n=77) and 10 yrs (n=149), and was better than hsTnT (AUC≤0.70). Addition of suPAR improved the mortality ROC curve of NT-proBNP (0.84 to 0.87) and for hsTnT (0.70 to 0.81) for 2-yr death prediction (Figure). Alone, suPAR was the strongest predictor (AUC=0.77) of new unstable angina at 2-yrs (n=52). The fully adjusted hazard ratio (HR) using Cox models showed suPAR (HR: 1.2) and NT-proBNP (HR: 1.3) to be the only independent biomarkers associated with death at 4 and 10-yrs (P<0.0001). Stratification of baseline suPAR by Kaplan-Meier plots for all-cause mortality showed the highest tertile of suPAR, compared to the lowest, was associated with a HR of 5.7 and 5.1 for 4-yr and 10-yr death, respectively. Conclusion: suPAR is a strong prognostic indicator of long-term mortality and its usage alongside current cardiac biomarkers may assist in the risk stratification of AMI patients. Funding Acknowledgement: Type of funding source: Foundation. Main funding source(s): Health Research Council of New Zealand, National Heart Foundation of New Zealand