Plasma DPP4 activity is associated with no-reflow and major bleeding events in Chinese PCI-treated STEMI patients

Abstract

Dipeptidyl peptidase-4 (DPP4) is an important regulator of incretins and inflammation, and it is involved in the pathophysiological process of myocardial infarction (MI). This study investigated the role of plasma DPP4 activity (DPP4a) in patients with ST-segment elevation myocardial infarction (STEMI) who had undergone percutaneous coronary intervention (PCI). We recruited 747 consecutive PCI-treated STEMI patients from a tertiary referral center from January 2014 to October 2015. The outcomes of interest were the rates of no-reflow, in-hospital major adverse cardiac or cerebrovascular events (iMACCE), in-hospital complications (IHC) and in-hospital major bleeding. The DPP4a was lower in STEMI patients compared with the controls (p < 0.0001). Multivariate logistic-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase in DPP4a was associated with an increased rate of no-reflow events (odds ratio [OR]: 1.07; 95% CI: 1.02–1.11; p < 0.01) and a decreased rate of major bleeding events (OR: 0.90; 95% CI: 0.82–0.98; p = 0.02). There were no associations between DPP4a and either iMACCE or IHC. In conclusions, high levels of DPP4a are independently associated with an increased rate of no-reflow events and a decreased rate of major bleeding events in PCT-treated STEMI patients.

Reduced post-operative DPP4 activity associated with worse patient outcome after cardiac surgery

“…However, in our study cohort, no significant correlation was detected between BMI and serum DPP4 activity. This is in accordance with previous findings in STEMI patients, in whom no difference was detected in BMI among different quartiles of plasma DPP4 activity 39 , 54 . In contrast, as mentioned earlier, patients with a recent myocardial infarction exhibited a significantly reduced pre-operative DDP4 activity when compared to patients without recent infarction.…”

“…Further, DPP4 activity decreased during cardiac surgery with CPB, if not already decreased by a recent myocardial infarction or severely reduced LVEF. Although this contrasts earlier experimental findings of hypoxia-induced shedding of membrane DPP4 from vascular cells 20 , 55 , our findings are in line with a clinical study in STEMI patients showing reduced plasma DPP4 activity after myocardial infarction 54 . Also, hypoxia treatment of adipocytes significantly reduced the activity of shedded DPP4 56 , although the underlying mechanisms remained unclear.…”

Prognostic value of plasma DPP4 activity in ST-elevation myocardial infarction

“…Although a previous study has shown that DPP4a was higher in diabetic populations [ 12 , 31 ], this trend was not observed in the current study. However, DPP4a is reduced after MI [ 13 ], thus diabetic patients may have more severe DPP4a reductions after STEMI than non-diabetic patients.…”

“…Fast plasma glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, N-terminal pro B-type natriuretic peptide (NT-proBNP), creatinine, creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) levels were measured using automated enzymatic methods (Cobas ® , Roche, Germany). DPP4 activities were determined in EDTA-treated plasma samples by measuring rates of p-nitroaniline (pNa) cleavage from the synthetic substrate H-Gly-Pro-pNa (L1880, Bachem, Switzerland) by DPP4, as previously described [ 13 ]. Briefly, 5 µL plasma samples were added to 150 µL of 50 mM tris–HCl containing 1 mM H-Gly-Pro-pNa.…”

“…Additionally, DPP4a correlated with adverse cardiovascular outcomes in HF [ 11 ] as well as sub-clinical left ventricular dysfunction in diabetic patients [ 12 ]. Our previous work found that DPP4a was significantly lower in MI patients compared with patients experiencing only chest pain or unstable angina, and DPP4a associated with inpatient no-reflow and major bleeding events in STEMI patients [ 13 ]. The no-reflow phenomenon [ 14 ] and major bleeding events [ 15 ] independently associated with worsened in-hospital and long-term prognoses.…”