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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^_*,,5,_*, Ewa A. Jankowska, MD, 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, Joachim Struck, PhD^,1,2, Piotr Ponikowski, MD, PhD, Andreas Bergmann, PhD^,1,2,3 and Stefan D. Anker, MD, PhD^_*,,4

^_* Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany
Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom
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