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 2months; 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 3years 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 3years 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.