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CLINICAL RESEARCH: HEART FAILURE

Comparison of Copeptin, B-Type Natriuretic Peptide, and Amino-Terminal Pro-B-Type Natriuretic Peptide in Patients With Chronic Heart Failure

Prediction of Death at Different Stages of the Disease

Stephanie Neuhold, MD^_*, Martin Huelsmann, MD^_*,_*, Guido Strunk, PhD, Brigitte Stoiser, MD, Joachim Struck, PhD, Nils G. Morgenthaler, MD, Andreas Bergmann, PhD, Deddo Moertl, MD^_*, Rudolf Berger, MD^_* and Richard Pacher, MD^_*

^_* Department of Cardiology, Medical University of Vienna, Vienna, Austria
Department of Infectious Diseases, Medical University of Vienna, Vienna, Austria
Research Institute for Health Care Management and Economics, University of Economics and Business Administration, Vienna, Austria
B.R.A.H.M.S. AG, Hennigsdorf, Germany.

Manuscript received December 20, 2007; revised manuscript received March 10, 2008, accepted March 18, 2008.

^_* Reprint requests and correspondence: Dr. Martin Huelsmann, Medical University of Vienna, Department of Cardiology, Waehringer Guertel 18-20, 1090 Vienna, Austria. (Email: martin.huelsmann{at}meduniwien.ac.at).

Objectives: This study sought to evaluate the predictive value of copeptin over the entire spectrum of heart failure (HF) and compare it to the current benchmark markers, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Background: Vasopressin has been shown to increase with the severity of chronic HF. Copeptin is a fragment of pre–pro-vasopressin that is synthesized and secreted in equimolar amounts to vasopressin. Both hormones have a short lifetime in vivo, similar to BNPs, but in contrast to vasopressin, copeptin is very stable in vitro. The predictive value of copeptin has been shown in advanced HF, where it was superior to BNP for predicting 24-month mortality.

Methods: This was a long-term observational study in 786 HF patients from the whole spectrum of heart failure (New York Heart Association [NYHA] functional class I to IV, BNP 688 ± 948 pg/ml [range 3 to 8,536 pg/ml], left ventricular ejection fraction 25 ± 10% [range 5% to 65%]).

Results: The NYHA functional class was the most potent single predictor of 24-month outcome in a stepwise Cox regression model. The BNP, copeptin, and glomerular filtration rate were related to NYHA functional class (p < 0.0001 for trend). Copeptin was the most potent single predictor of mortality in patients with NYHA functional class II (p < 0.0001) and class III (p < 0.0001). In NYHA functional class IV, the outcome of patients was best predicted by serum sodium, but again, copeptin added additional independent information.

Conclusions: Increased levels of copeptin are linked to excess mortality, and this link is maintained irrespective of the clinical signs of severity of the disease. Copeptin was superior to BNP or NT-proBNP in this study, but the markers seem to be closely related.

Key Words: BNP • vasopressin • heart failure • prognosis

Abbreviations and Acronyms   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   GFR = glomerular filtration rate   LVEF = left ventricular ejection fraction   NT-proANP = N-terminal pro-atrial natriuretic peptide   NT-proBNP = N-terminal pro-B-type natriuretic peptide   NYHA = New York Heart Association   ROC = receiver-operator characteristic

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