1Uniklinik RWTH Aachen Med. Klinik I - Kardiologie, Angiologie und Internistische Intensivmedizin Aachen, Deutschland; 2Sphingotec GmbH Hennigsdorf, Deutschland; 34TEEN4 Pharmaceuticals GmbH Hennigsdorf, Deutschland; 4Uniklinik RWTH Aachen Med. Klinik V - Klinik für Pneumologie und Internistische Intensivmedizin Aachen, Deutschland; 5Universitätsklinikum Heidelberg Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie Heidelberg, Deutschland
Background: Dipeptidyl peptidase 3 (DPP3) is an enzyme involved in the degradation of cardiovascular and endorphin mediators. In pre-clinical studies of sepsis and acute heart failure in rodents, inhibition of circulating DPP3 normalized cardiac function. A recent study found cDPP3 levels to be associated with mortality in patients with acute coronary syndrome (ACS) and cardiogenic shock. The aim of the study was to evaluate whether circulating DPP3 adds predictive information to the Global Registry of Acute Coronary Events (GRACE) score, a validated scoring system for risk assessment in patients with ACS.
Methods: cDPP3 concentrations were assessed at time of admission in 1,810 patients (cohort 1: n=694 patients; cohort 2: n=1,116 patients) admitted to the emergency department with acute myocardial infarction. The primary outcome of the study was first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3-P-MACE) with a median follow-up of 311 days.
Results: In the derivation cohort (n=694) univariable Cox regression analyses found cDPP3 to be associated with 3-P-MACE (HR: 1.7, 95% CI: 1.2-2.6; p = 0.007). After adjustment for traditional CV risk factors, GFR CKD-EPI, hs-CRP, hs-Troponin T and NT-proBNP, the adjusted standardized HR remained significant at 1.6 (95% CI: 1.1-2.6; p = 0.0002). We found similar results for all-cause mortality. Addition of cDPP3 improved predictive capacity of the GRACE score for 3-P-MACE (delta C index: 0.031, delta Chi2: 6.10, p<.0001) and all-cause mortality (delta C index: 0.022, delta Chi2: 5.40, p<.0001). Improvement of the GRACE score after addition of cDPP3 was confirmed in an independent validation cohort (n = 1,116) for 3-P-MACE (delta C index: 0.026, delta Chi2: 5.93, p=0.0028) and all-cause mortality (delta C index: 0.026, delta Chi2: 10.00, p<.0001).
Conclusion: cDPP3 is a predictor of cardiovascular outcomes and provides added value on top of the GRACE risk score in patients with acute myocardial infarction.