Proenkephalin and the risk of new-onset heart failure: data from prevention of renal and vascular end-stage disease

Abstract

Background: Enkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new-onset HF in the general population remains to be established. Hypothesis: We hypothesized that plasma PENK concentrations are associated with new-onset HF in the general population. Methods: We included 6677 participants from the prevention of renal and vascular end-stage disease study and investigated determinants of PENK concentrations and their association with new-onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]). Results: Median PENK concentrations were 52.7 (45.1–61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT-proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p