Dipeptidyl peptidase-IV in chronic heart failure with reduced ejection fraction

Background An association between dipeptidyl peptidase-IV (DPP-IV) inhibitors with worse prognosis in HF has been suggested. We aimed to assess the serum DPP-IV levels in chronic stable HF patients and determine their association with prognosis. Methods and results Chronic stable HF patients with optimized prognostic-modifying therapy were prospectively recruited. Exclusion criteria: 1) ejection fraction > 50%, 2) hospitalizations or therapeutic adjustments in the previous 2 months; 3) patients on renal replacement therapy, and 4) use of DPP-IV inhibitors. A fasting venous blood sample was collected and DPP-IV was measured. Patients were followed-up for 3 years and the endpoint studied was all-cause death. Patients' characteristics were compared according to DPP-IV quartiles. A Cox regression analysis was performed and multivariate models were built. The 3rd DPP-IV quartile was the reference category. We studied 264 patients. Mean age: 69 (± 13) years, 70.5% were male and 33.7% diabetic. Median (IQR) serum DPP-IV levels were 455.6 (350.0–625.5) ng/mL. DPP-IV had an inverse relationship with age. Patients in 3rd DPP-IV quartile were in lower NYHA classes and had the lowest 3 years all-cause mortality. Patients in the 1st DPP-IV quartile had a multivariate adjusted HR of 3-year mortality of 2.62 (95%CI: 1.15–5.95) when compared with reference category and the HR for the 4th quartile was of 3.79 (95%CI: 1.68–8.54). Conclusions There is a U-shaped association of serum DPP-IV with mortality in chronic systolic HF patients. Patients in the 3rd DPP-IV quartile have the best multivariate adjusted 3-year survival. DPP-IV inhibition might be harmful in patients with low DPP-IV.This article is a result of the project DOCnet (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)