Soluble urokinase-type plasminogen activator receptor represents exercise tolerance and predicts adverse cardiac events in patients with heart failure

Soluble urokinase-type plasminogen activator receptor (suPAR) is a membrane-binding protein that is released into the blood stream by immune activation. Recent reports suggest that circulating suPAR levels are associated with adverse cardiovascular outcomes. Exercise tolerance is an independent predictor of prognosis in patients with heart failure (HF); however, the relationship between serum suPAR level and exercise tolerance is unclear. We prospectively enrolled 94 patients who were hospitalized for worsening of HF. All patients underwent a symptom-limited cardiopulmonary exercise test to evaluate exercise tolerance. The median value of serum suPAR was 4848 pg/ml. During follow up, 44 patients (47%) were admitted for all-cause mortality and re-hospitalization for HF. Median serum suPAR was significantly higher in the patients with cardiac events than in the patients with non-event group. Patients were divided into two groups according to circulating suPAR levels. Kaplan–Meier analysis demonstrated that adverse cardiac events were significantly higher in the high suPAR group (log-rank p = 0.023). Multivariate analysis revealed that suPAR was independently correlated with the parameters of exercise tolerance such as anaerobic threshold (p = 0.007) and peak oxygen uptake (p = 0.005). suPAR levels predicted adverse cardiac events and independently correlated with the parameters of exercise tolerance. suPAR could be a useful surrogate biomarker of exercise tolerance in patients with HF.