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J Am Coll Cardiol, 2007; 50:1973-1980, doi:10.1016/j.jacc.2007.08.012 (Published online 29 October 2007).
© 2007 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: BIOMARKER

Comparison of Midregional Pro-Atrial Natriuretic Peptide With N-Terminal Pro-B-Type Natriuretic Peptide in Predicting Survival in Patients With Chronic Heart Failure

Stephan von Haehling, MD*,{dagger},5,*, Ewa A. Jankowska, MD{ddagger}, Nils G. Morgenthaler, MD§,1, Corrado Vassanelli, MD||, Luisa Zanolla, MD||, Piotr Rozentryt, MD, Gerasimos S. Filippatos, MD#, Wolfram Doehner, MD, PhD*, Friedrich Koehler, MD**, Jana Papassotiriou, PhD§, Dimitrios T. Kremastinos, MD, PhD#, Waldemar Banasiak, MD{ddagger}, Joachim Struck, PhD§,1,2, Piotr Ponikowski, MD, PhD{ddagger}, Andreas Bergmann, PhD§,1,2,3 and Stefan D. Anker, MD, PhD*,{dagger},4

* Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany
{dagger} Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom
{ddagger} Cardiology Department, Military Hospital, Wroclaw, Poland
§ Research Department, B.R.A.H.M.S Aktiengesellschaft, Biotechnology Centre, Hennigsdorf/Berlin, Germany
|| Department of Biomedical and Surgical Sciences, Section of Cardiology, University of Verona, Verona, Italy
Third Department of Cardiology, Silesian Center for Heart Disease, Zabrze, Poland
# Second University Department of Cardiology, Atticon University Hospital, Athens, Greece
** Charité Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.

Manuscript received October 11, 2006; revised manuscript received July 12, 2007, accepted August 14, 2007.

* Reprint requests and correspondence: Dr. Stephan von Haehling, Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. (Email: stephan.von.haehling{at}web.de).

Objectives: Our aim was assess the prognostic value of midregional pro-atrial natriuretic peptide (MR-proANP) using a new immunoassay in patients with chronic heart failure (HF).

Background: Assessment of natriuretic peptides represents a useful addition in establishing the diagnosis of chronic HF. Their plasma values are powerful predictors of survival in chronic HF.

Methods: We assessed MR-proANP in 525 chronic HF patients (derivation study: age 61 ± 12 years, New York Heart Association (NYHA) functional class I/II/III/IV 6%/44%/41%/9%, N-terminal pro-B-type natriuretic peptide (NT-proBNP) 3,637 ± 6,362 pg/ml) and validated our findings in 249 additional chronic HF patients (age 63 ± 9 years, NYHA functional class I/II/III/IV 14%/50%/33%/3%, NT-proBNP 1,116 ± 1,991 pg/ml).

Results: The MR-proANP levels (mean 339 ± 306 pmol/l, range 24.5 to 2,280 pmol/l) increased with NYHA funcitonal class (p < 0.0001). During follow-up (>6 months in survivors), 171 patients (33%) died. Increasing MR-proANP was a predictor of poor survival (risk ratio 1.35 per increase in standard deviation, 95% confidence interval 1.17 to 1.57; p = 0.0061), adjusted for NT-proBNP, age, left ventricular ejection fraction, NYHA functional class, creatinine, and body mass index (BMI). In receiver operating characteristic curve analysis of 12-month survival, the area under the curve for MR-proANP was 0.74 and that of NT-proBNP was 0.75 (p = 0.7). In a validation study, MR-proANP levels above the optimal prognostic cutoff value from the validation cohort remained a significant independent predictor of death. In chronic HF patients in NYHA functional class II to III and all subgroups of BMI and kidney function, MR-proANP added prognostic value to NT-proBNP. In patients with BMI ≥30 kg/m2, MR-proANP had higher prognostic power than NT-proBNP.

Conclusions: Midregional proANP is an independent predictor of mortality in patients with chronic HF. Midregional proANP adds prognostic information to NT-proBNP.

Abbreviations and Acronyms
  AUC = area under the receiver-operating characteristic curve
  HF = heart failure
  LVEF = left ventricular ejection fraction
  MR-proANP = midregional pro-atrial natriuretic peptide
  NT-proBNP = N-terminal pro-B-type natriuretic peptide
  NYHA = New York Heart Association
  ROC = receiver-operating characteristic




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