Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure

J Card Fail. 2017 Mar;23(3):231-239. doi: 10.1016/j.cardfail.2016.09.007. Epub 2016 Sep 20.


Background: Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure.

Methods and results: The association between pro-ENK and markers of renal function was evaluated in 95 patients with chronic heart failure who underwent renal hemodynamic measurements, including renal blood flow (RBF) and glomerular filtration rate (GFR) with the use of 131I-Hippuran and 125I-iothalamate clearances, respectively. The association between pro-ENK and clinical outcome in acute heart failure was assessed in another 1589 patients. Pro-ENK was strongly correlated with both RBF (P < .001) and GFR (P < .001), but not with renal tubular markers. In the acute heart failure cohort, pro-ENK was a predictor of death through 180 days, heart failure rehospitalization through 60 days, and death or cardiovascular or renal rehospitalization through day 60 in univariable analyses, but its predictive value was lost in a multivariable model when other renal markers were entered in the model.

Conclusions: In patients with chronic and acute heart failure, pro-ENK is strongly associated with glomerular function, but not with tubular damage. Pro-ENK provides limited prognostic information in patients with acute heart failure on top of established renal markers.

Keywords: Renal function; enkephalin; heart failure; prognosis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Biomarkers / blood
  • Enkephalins / blood*
  • Female
  • Glomerular Filtration Rate
  • Heart Failure / blood*
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology
  • Humans
  • Kidney / physiopathology*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Protein Precursors / blood*
  • Xanthines / therapeutic use*


  • Biomarkers
  • Enkephalins
  • Protein Precursors
  • Xanthines
  • proenkephalin
  • rolofylline