Circulating dipeptidyl peptidase 3 predicts hemodynamic impairment and premature death in acute coronary syndromes: insights from the prospective multicenter SPUM-ACS study

Abstract Background Dipeptidyl peptidase 3 (DPP3) is mechanistically involved in the degradation of angiotensin II and in the depression of systolic left ventricular function thereby disturbing peripheral blood pressure regulation. Small pilot studies suggested that circulating DPP3 (cDPP3) portends poor outcomes in acute heart failure and may refine risk assessment in patients with acute coronary syndromes (ACS). Purpose We aimed to assess the predictive value of cDPP3 in contemporary patients with ACS. Methods Circulating DPP3 was studied in 4311 patients with ACS in the prospective multicentre SPUM-ACS study. DPP3 levels were centrally measured in EDTA plasma by blinded study personnel using an established sandwich-type luminometric immunoassay. Kaplan-Meier survival curves and multivariable-adjusted regression models adjusted for sex, age, heart rate, systolic blood pressure, history of diabetes, levels of creatinine, centrally measured high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein, and the Global Registry of Acute Coronary Events (GRACE) risk score. Results At baseline, median cDPP3 levels were 19.0 ng/ml (interquartile range [IQR] 15.0-26.0) with higher levels observed in patients with ST-segment elevation myocardial infarction than in those with non-ST-segment elevation ACS (20.1 [15.9-28.2] vs. 18.0 [14.1-23.9], respectively, P<0.001). High cDPP3 was linked to longer hospitalization and higher risk to require vasopressor use or mechanical circulatory support (per log2 increase: odds ratio [OR] 1.91, 95% confidence interval [CI] 1.62-2.24, P<0.001; adjusted OR 1.35 95% CI 1.08-1.69, P=0.008). In line, high cDPP was strongly associated with increased mortality at 30 days (per log2 increase: hazard ratio [HR] 1.96, 95% CI 1.48-2.59, P<0.001) and at 1 year (HR 1.51, 95% CI 1.24-1.83, P<0.001). When accounting for established risk factors, cDPP3 remained an independent predictor of premature death with doubling in cDPP3 levels translating into an 58% and 40% increase in 30-day and 1-year mortality risk, respectively (adjusted HR 1.58, 95% CI 1.06-2.34, P<0.023, adjusted HR 1.40, 95% CI 1.10-1.77, P=0.006, respectively). Conclusion We identified cDPP3 as a novel marker of cardiogenic shock and increased mortality in patients with ACS. Circulating DPP3 provides prognostic information beyond established risk factors and improves early risk assessment.DPP3 is linked to hemodynamic impairmentDPP3 independently predicts mortality