title: Midregional proadrenomedullin and growth differentiation factor-15 are not influenced by obesity in heart failure patients.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sinning
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ojeda
authors.affiliation: Department of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.|Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Wild
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarzl
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Sevenai
authors.initials: S
authors.lastname: Ohdah
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: Department of Ophthalmology, University Medical Center, Mainz, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany.|Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Michal
authors.affiliation: Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) at the University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Blettner
authors.affiliation: Department of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Munzel
authors.affiliation: Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.affiliation: Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.affiliation: Department of Health, National Institute for Health and Welfare, Oulu, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Kuulasmaa
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Department of Health, National Institute for Health and Welfare, Oulu, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Westermann
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany. t.zeller@uke.de.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany. t.zeller@uke.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000401:mortality; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); C088633:proadrenomedullin; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor
keywords: Growth differentiation factor-15; Heart failure; MR-proADM; NT-proBNP; Natriuretic peptides; Obesity