Proenkephalin, Renal Dysfunction, and Prognosis in Patients With Acute Heart Failure

TY - JOUR

T1 - Proenkephalin, Renal Dysfunction, and Prognosis in Patients With Acute Heart Failure

T2 - A GREAT Network Study

AU - Ng, Leong L.

AU - Squire, Iain B.

AU - Jones, Donald J.L.

AU - Cao, Thong Huy

AU - Chan, Daniel C.S.

AU - Sandhu, Jatinderpal K.

AU - Quinn, Paulene A.

AU - Davies, Joan E.

AU - Struck, Joachim

AU - Hartmann, Oliver

AU - Bergmann, Andreas

AU - Mebazaa, Alexandre

AU - Gayat, Etienne

AU - Arrigo, Mattia

AU - Akiyama, Eiichi

AU - Sabti, Zaid

AU - Lohrmann, Jens

AU - Twerenbold, Raphael

AU - Herrmann, Thomas

AU - Schumacher, Carmela

AU - Kozhuharov, Nikola

AU - Mueller, Christian

N1 - Publisher Copyright: © 2017 American College of Cardiology Foundation

PY - 2017/1/3

Y1 - 2017/1/3

N2 - Background Proenkephalin A (PENK) and its receptors are widely distributed. Enkephalins are cardiodepressive and difficult to measure directly. PENK is a stable surrogate analyte of labile enkephalins that is correlated inversely with renal function. Cardiorenal syndrome is common in acute heart failure (HF) and portends poor prognosis. Objectives This study assessed the prognostic value of PENK in acute HF, by identifying levels that may be useful in clinical decisions, and evaluated its utility for predicting cardiorenal syndrome. Methods This multicenter study measured PENK in 1,908 patients with acute HF (1,186 male; mean age 75.66 ± 11.74 years). The primary endpoint was 1-year all-cause mortality; secondary endpoints were in-hospital mortality, all-cause mortality or HF rehospitalization within 1 year, and in-hospital worsening renal function, defined as a rise in plasma creatinine ≥26.5 μmol/l or 50% higher than the admission value within 5 days of presentation. Results During 1-year follow-up, 518 patients died. Measures of renal function were the major determinants of PENK levels. PENK independently predicted worsening renal function (odds ratio: 1.58; 95% confidence interval [CI]: 1.24 to 2.00; p < 0.0005) with a model receiver-operating characteristic area of 0.69. PENK was associated with the degree of worsening renal function. Multivariable Cox regression models showed that PENK level was an independent predictor of 1-year mortality (p < 0.0005) and 1-year death and/or HF (hazard ratio: 1.27; 95% CI: 1.10 to 1.45; p = 0.001). PENK levels independently predicted outcomes at 3 or 6 months and were independent predictors of in-hospital mortality, predominantly down-classifying risk in survivors when added to clinical scores; levels <133.3 pmol/l and >211.3 pmol/l detected low-risk and high-risk patients, respectively. Conclusions PENK levels reflect cardiorenal status in acute HF and are prognostic for worsening renal function and in-hospital mortality as well as mortality during follow-up.

AB - Background Proenkephalin A (PENK) and its receptors are widely distributed. Enkephalins are cardiodepressive and difficult to measure directly. PENK is a stable surrogate analyte of labile enkephalins that is correlated inversely with renal function. Cardiorenal syndrome is common in acute heart failure (HF) and portends poor prognosis. Objectives This study assessed the prognostic value of PENK in acute HF, by identifying levels that may be useful in clinical decisions, and evaluated its utility for predicting cardiorenal syndrome. Methods This multicenter study measured PENK in 1,908 patients with acute HF (1,186 male; mean age 75.66 ± 11.74 years). The primary endpoint was 1-year all-cause mortality; secondary endpoints were in-hospital mortality, all-cause mortality or HF rehospitalization within 1 year, and in-hospital worsening renal function, defined as a rise in plasma creatinine ≥26.5 μmol/l or 50% higher than the admission value within 5 days of presentation. Results During 1-year follow-up, 518 patients died. Measures of renal function were the major determinants of PENK levels. PENK independently predicted worsening renal function (odds ratio: 1.58; 95% confidence interval [CI]: 1.24 to 2.00; p < 0.0005) with a model receiver-operating characteristic area of 0.69. PENK was associated with the degree of worsening renal function. Multivariable Cox regression models showed that PENK level was an independent predictor of 1-year mortality (p < 0.0005) and 1-year death and/or HF (hazard ratio: 1.27; 95% CI: 1.10 to 1.45; p = 0.001). PENK levels independently predicted outcomes at 3 or 6 months and were independent predictors of in-hospital mortality, predominantly down-classifying risk in survivors when added to clinical scores; levels <133.3 pmol/l and >211.3 pmol/l detected low-risk and high-risk patients, respectively. Conclusions PENK levels reflect cardiorenal status in acute HF and are prognostic for worsening renal function and in-hospital mortality as well as mortality during follow-up.

KW - acute kidney injury

KW - B-type natriuretic peptide

KW - mortality

KW - net reclassification improvement

KW - opioids

UR - http://www.scopus.com/inward/record.url?scp=85009144911&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2016.10.038

DO - 10.1016/j.jacc.2016.10.038

M3 - SCORING: Journal article

C2 - 28057251

AN - SCOPUS:85009144911

VL - 69

SP - 56

EP - 69

JO - J AM COLL CARDIOL

JF - J AM COLL CARDIOL

SN - 0735-1097

IS - 1

ER -