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Original article
Serial measurements of midregion proANP and copeptin in ambulatory patients with heart failure: incremental prognostic value of novel biomarkers in heart failure
  1. Wayne L Miller1,
  2. Karen A Hartman1,
  3. Diane E Grill2,
  4. Joachim Struck3,
  5. Andreas Bergmann3,
  6. Allan S Jaffe1,4
  1. 1Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
  2. 2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
  3. 3BRAHMS Aktiengesellschaft (Part of ThermoFisher Scientific), Hennigsdorf, Germany
  4. 4Department of Laboratory, Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr Wayne L Miller, Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA; miller.wayne{at}


Background Disease progression in heart failure (HF) reflects derangements in neurohormonal systems, and biomarkers of these systems can help to establish the diagnosis and assess the prognosis. Serial measurements of the precursor peptides of the natriuretic and vasopressin systems (midregional proatrial natriuretic peptide (MR-proANP) and C-terminal provasopressin (copeptin), respectively) should add incremental value to risk stratification in ambulatory patients with HF.

Methods and results A cohort of 187 patients with class III–IV HF was prospectively enrolled, with biomarkers collected every 3 months over 2 years and analysed in relation to death/transplantation. Time-dependent analyses (dichotomous and continuous variables) showed that increases in MR-proANP (HR 7.6, 95% CI 1.85 to 31.15, p<0.01) and copeptin (HR 2.7, 95% CI 1.27 to 5.61, p=0.01) were associated with increased risk, but, in multivariate analysis adjusted for troponin T (cTnT) ≥0.01 ng/ml, only raised MR-proANP remained an independent predictor (HR 5.49, 95% CI 1.31 to 23.01, p=0.02). Combined increases in MR-proANP and copeptin (HR 9.01, 95% CI 1.24 to 65.26, p=0.03) with cTnT (HR 11.1, 95% CI 1.52 to 80.85, p=0.02), and increases ≥30% above already raised values identified the patients at greatest risk (MR-proANP: HR 10.1, 95% CI 2.34 to 43.38, p=0.002; copeptin: HR 11.5, 95% CI 2.74 to 48.08, p<0.001).

Conclusions A strategy of serial monitoring of MR-proANP and, of lesser impact, copeptin, combined with cTnT, may be advantageous in detecting and managing the highest-risk outpatients with HF.

  • MR-pro-ANP
  • CT-pro-vasopressin (copeptin)
  • chronic heart failure
  • outcomes
  • heart failure
  • heart failure treatment
  • acute coronary syndrome
  • acute myocarditis
  • coronary heart disease
  • natriuretic peptides
  • troponin t
  • acute myocardial infarction

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: and

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  • Funding This work was supported in part by a grant from Siemens (Newark, Delaware, USA). Reagents were supplied by BRAHMS, now ThermoFisher Scientific (Richmond, Virginia, USA).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Mayo Clinic Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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