Soluble urokinase plasminogen activator receptor for risk stratification from undifferentiated acute chest pain through to convalescence after acute coronary syndromes

Aims The performance of plasma soluble urokinase plasminogen activator receptor (suPAR) for prediction of heart failure (HF) readmission or death within 5 years was assessed in patients incurring (i) initially undifferentiated chest pain and (ii) immediately after diagnosed with acute coronary syndromes (ACS), and (iii) in recovery after ACS. Methods and results Soluble urokinase plasminogen activator receptor concentrations were measured at admission for acute chest pain patients (n = 917) including confirmed ACS (26.5%) and in an independent 4–6-week post-ACS cohort (n = 1301). Soluble urokinase plasminogen activator receptor’s prognostic performance, in comparison, and combination with cardiac troponin I or n-terminal-pro B-type natriuretic peptide (NT-proBNP) was evaluated by risk discrimination, hazard ratios (HRs) as continuous variables, and cut-off concentrations across the three settings in unadjusted and adjusted analyses. In acute undifferentiated chest pain including the subgroup with confirmed ACS and separately post-ACS convalescence, combining suPAR and NT-proBNP yielded the highest discriminatory power for endpoints (c-statistics >0.80, ≥Δ0.02). Soluble urokinase plasminogen activator receptor in the acute and post-ACS convalescent conferred additional hazard for the composite endpoint of HF/death (HR > 1.4), HF (HR > 1.3), and death (HR > 1.2) after adjustment for risk factors including circulating cardiac markers. Although suPAR > 3.65 ng/mL (>83% specificity, > 91% negative predictive value (NPV) was superior in admission-ACS (HR, 10.5) for risk of HF/death, independent prediction for the composite endpoint remained consistent across the three settings and in men. Conclusion Plasma suPAR independently predicted risk of readmissions with HF and death, independent of key clinical indicators and cardiac markers at all points of the patient journey from acute chest pain presentation through to post-ACS convalescence. Its use in acute chest pain and ACS may augment risk stratification strategies.