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


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 of131I-Hippuran and125I-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.
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Yuya
Y
Matsue
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Jozine M
JM
Ter Maaten
Sphingotec GmbH, Hennigsdorf, Germany.
Joachim
J
Struck
University of Brescia, Brescia, Italy.
Marco
M
Metra
Inova Heart and Vascular Institute, Falls Church, Virginia.
Christopher M
CM
O'Connor
Clinical Military Hospital, Medical University, Wroclaw, Poland.
Piotr
P
Ponikowski
University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California.
John R
JR
Teerlink
Momentum Research, Durham, North Carolina.
Gad
G
Cotter
Momentum Research, Durham, North Carolina.
Beth
B
Davison
University of Hull, Kingston upon Hull, United Kingdom.
John G
JG
Cleland
Brigham and Women's Hospital, Boston, Massachusetts.
Michael M
MM
Givertz
Merck Research Laboratories, Rahway, New Jersey.
Daniel M
DM
Bloomfield
Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa.
Howard C
HC
Dittrich
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Dirk J
DJ
van Veldhuisen
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Peter
P
van der Meer
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Kevin
K
Damman
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: a.a.voors@umcg.nl.
Adriaan A
AA
Voors
D000208:Acute Disease; D015415:Biomarkers / Q000097:blood; D004745:Enkephalins / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood*; D014970:Xanthines / Q000627:therapeutic use*
D015415:Biomarkers; D004745:Enkephalins; D011498:Protein Precursors; D014970:Xanthines; C029992:proenkephalin; C073525:rolofylline
Renal function; enkephalin; heart failure; prognosis