Background: Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. Its intravenous administration has been shown to impair cardiac function in rodents. In a pre-clinical model of severe heart failure in mice, inhibition of DPP3 by a monoclonal antibody normalized cardiac and renal function. The aim of this study was to assess the predictive capacity of DPP3 for cardiovascular outcome in patients with myocardial infarction. 

Methods: Circulating DPP3 levels, NT-proBNP, hs-CRP, Troponin T concentrations and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of admission in 694 patients with myocardial infarction presenting with acute chest pain. The primary composite outcome of the study was first occurrence of cardiovasvular death, non-fatal myocardial infarction, or non-fatal stroke (3-P-MACE) with a median follow-up of 311 days. 

Results: Median DPP3 was 30.2 ng/ml (inter-quartile range 22.3-40.8 ng/ml), and n=44 3-P-MACE events were observed during the 1 year follow up period. Univariable Cox regression analyses found DPP3 to be associated with 3-P-MACE [standardized hazard ratio (HR) of DPP3 values: 1.7, 95% confidence interval (CI): 1.2-2.6; c index 0.63, p=0.007]. For DPP3 values above the third quartile, the standardized HR was 2.1 [1.2-3.8]. After further adjustment for age, sex, hypertension, history of cardiovascular disease, smoking, creatinine, hs-CRP, Troponin T and NT-proBNP levels, the adjusted standardized HR remained significant at 1.7 (95% CI: 1.1-2.6; p = 0.020). Adjustment of the GRACE risk estimate by addition of DPP3 increased the area under the receiver operating characteristic curve after 1 year from 0.69 to 0.71 and provided significant added value (increase in Chi² from 14.0 for GRACE to 20.1 for GRACE + DPP3, p= 0.0136) for 3-P-MACE prediction. Time-dependent receiver operating characteristic curve analyses illustrated that DPP3 proved to be particularly strong for 30-day 3-P-MACE prediction (c index 0.66). We found similar results for cardiovascular and all-cause mortality. 

Conclusion: DPP3 is independently associated with adverse cardiovascular outcomes and improves the predictive value of the GRACE score in patients with acute myocardial infarction. Future studies are needed to investigate whether DPP3 could be a novel therapeutical target for cardiovascular disease.