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Midregional proadrenomedullin and growth differentiation factor-15 are not influenced by obesity in heart failure patients

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Abstract

Background

Obesity is a risk factor for heart failure (HF) and identification of symptomatic, and obese HF patients are challenging, because obesity can mimic HF symptoms. We aimed to evaluate novel biomarkers for HF in obese subjects of the general population.

Methods

Midregional proadrenomedullin (MR-proADM), growth differentiation factor-15 (GDF-15), midregional pro-atrial natriuretic peptide (MR-proANP), and NT-proBNP were measured in 5000 individuals of the population-based Gutenberg Health Study (GHS), including 1204 obese individuals (BMI ≥ 30 kg/m2) and 107 individuals with HF.

Results

NT-proBNP and MR-proANP were lower in obese vs. non-obese HF individuals (p = 0.013 and p = 0.01, respectively), whereas GDF-15 was similar and MR-proADM was higher in obese vs. non-obese HF individuals. All biomarkers increased the odds ratio (OR) for prevalent HF. For NT-proBNP and MR-proANP, this increase was lower in obese vs. non-obese individuals, whereas it was comparable for MR-proADM and GDF-15. All biomarkers were associated with increased all-cause mortality (median follow-up 7.3 years, 211 events). Results were validated in 8373 individuals (n = 1734 with BMI ≥ 30 kg/m2) of the FINRISK study with a median follow-up of 13.8 years (1030 events). Using a dichotomized biomarker cutoff for HF, the best predictor for all-cause mortality in obese subjects was GDF-15 (p < 0.001).

Conclusion

All biomarkers were associated with HF and higher risk for all-cause mortality in the general population. In contrast to the natriuretic peptides NT-proBNP and MR-proANP, the novel biomarkers MR-proADM and GDF-15 were not lower in obese HF individuals, indicating their potential to facilitate HF diagnosis and prognosis in an increasingly obese HF population.

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Author information

Authors and Affiliations

  1. Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany

    Christoph Sinning, Francisco Ojeda, Renate B. Schnabel, Michael Schwarzl, Sevenai Ohdah, Stefan Blankenberg, Dirk Westermann & Tanja Zeller

  2. Department of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Philipp S. Wild & Thomas Munzel

  3. Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany

    Philipp S. Wild & Matthias Michal

  4. German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany

    Philipp S. Wild, Matthias Michal & Thomas Munzel

  5. German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany

    Renate B. Schnabel, Michael Schwarzl, Stefan Blankenberg, Dirk Westermann & Tanja Zeller

  6. Institute of Clinical Chemistry and Laboratory Medicine University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Karl J. Lackner

  7. Department of Ophthalmology, University Medical Center, Mainz, Germany

    Norbert Pfeiffer

  8. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz, Mainz, Germany

    Matthias Michal

  9. Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) at the University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Maria Blettner

  10. Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany

    Tibor Kempf & Kai C. Wollert

  11. Department of Health, National Institute for Health and Welfare, Oulu, Finland

    Kari Kuulasmaa & Veikko Salomaa

Authors
  1. Christoph Sinning
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  2. Francisco Ojeda
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  3. Philipp S. Wild
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  5. Michael Schwarzl
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  10. Maria Blettner
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  11. Thomas Munzel
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  12. Tibor Kempf
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  15. Stefan Blankenberg
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  18. Tanja Zeller
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Corresponding author

Correspondence to Tanja Zeller.

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Conflict of interest

Stefan Blankenberg has received research funding from Abbott, Abbott Diagnostics, Bayer, Boehringer Ingelheim, SIEMENS and Thermo Fisher. He received honoraria for lectures from Abbott, Abbott Diagnostics, Astra Zeneca, Bayer, Boehringer Ingelheim, Medtronic, Pfizer, Roche, SIEMENS Diagnostics, SIEMENS, Thermo Fisher and as member of Advisory Boards and for consulting for Boehringer Ingelheim, Bayer, Novartis, Roche and Thermo Fisher. Tibor Kempf and Kai C. Wollert are named co-inventors on a patent for the use of GDF-15 for cardiovascular applications and have a contract with Roche Diagnostics for the development of a GDF-15 assay. Kai C. Wollert has received research grant funding from Roche Diagnostics. All other co-authors did not report any conflict of interest.

Funding

This study was supported by the German Heart Foundation/German Foundation of Heart Research (Project: F/29/13 to C. Sinning) and by the German Center of Cardiovascular Research (DZHK to M. Schwarzl, D. Westermann and T. Zeller). This work has been supported by the European Union Seventh Framework Program (FP7/2007–2013) under grant agreement No. HEALTH-F2-2011-278913 (BiomarCaRE). The Gutenberg Health Study is funded through the research programs “Wissen schafft Zukunft” and “Schwerpunkt Vaskuläre Prävention” of the University Medical Center, Johannes Gutenberg-University Mainz, the government of Rheinland-Pfalz (“Stiftung Rheinland-Pfalz für Innovation”, AZ 961-386261/733), and Boehringer Ingelheim GmbH and Philips GmbH, including an unrestricted grant. V. Salomaa has been supported by the Finnish Foundation for Cardiovascular Research.

Additional information

D. Westermann and T. Zeller were equally senior author of the manuscript.

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Sinning, C., Ojeda, F., Wild, P.S. et al. Midregional proadrenomedullin and growth differentiation factor-15 are not influenced by obesity in heart failure patients. Clin Res Cardiol 106, 401–410 (2017). https://doi.org/10.1007/s00392-016-1066-x

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