Christoph Sinning1, Francisco Ojeda1, Philipp S Wild2,3,4, Renate B Schnabel1,5, Michael Schwarzl1,5, Sevenai Ohdah1, Karl J Lackner6, Norbert Pfeiffer7, Matthias Michal3,4,8, Maria Blettner9, Thomas Munzel2,4, Tibor Kempf10, Kai C Wollert10, Kari Kuulasmaa11, Stefan Blankenberg1,5, Veikko Salomaa11, Dirk Westermann1,5, Tanja Zeller12,13. 1. Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany. 2. Department of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. 3. Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany. 4. German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany. 5. German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany. 6. Institute of Clinical Chemistry and Laboratory Medicine University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. 7. Department of Ophthalmology, University Medical Center, Mainz, Germany. 8. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz, Mainz, Germany. 9. Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) at the University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. 10. Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. 11. Department of Health, National Institute for Health and Welfare, Oulu, Finland. 12. Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany. t.zeller@uke.de. 13. German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany. t.zeller@uke.de.
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.
BACKGROUND:Obesity is a risk factor for heart failure (HF) and identification of symptomatic, and obese HFpatients 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.
Authors: Philipp S Wild; Christoph R Sinning; Alexander Roth; Sandra Wilde; Renate B Schnabel; Edith Lubos; Tanja Zeller; Till Keller; Karl J Lackner; Maria Blettner; Ramachandran S Vasan; Thomas Münzel; Stefan Blankenberg Journal: Circ Cardiovasc Imaging Date: 2010-07-19 Impact factor: 7.792
Authors: Sandeep R Das; Mark H Drazner; Daniel L Dries; Gloria L Vega; Harold G Stanek; Shuaib M Abdullah; Russell M Canham; Anne K Chung; David Leonard; Frank H Wians; James A de Lemos Journal: Circulation Date: 2005-10-04 Impact factor: 29.690
Authors: Daniel G Krauser; Donald M Lloyd-Jones; Claudia U Chae; Renee Cameron; Saif Anwaruddin; Aaron L Baggish; Annabel Chen; Roderick Tung; James L Januzzi Journal: Am Heart J Date: 2005-04 Impact factor: 4.749
Authors: Lori B Daniels; Paul Clopton; Vikas Bhalla; Padma Krishnaswamy; Richard M Nowak; James McCord; Judd E Hollander; Philippe Duc; Torbjørn Omland; Alan B Storrow; William T Abraham; Alan H B Wu; Philippe G Steg; Arne Westheim; Cathrine Wold Knudsen; Alberto Perez; Radmila Kazanegra; Howard C Herrmann; Peter A McCullough; Alan S Maisel Journal: Am Heart J Date: 2006-05 Impact factor: 4.749
Authors: Michael H Olsen; Tine W Hansen; Marina K Christensen; Finn Gustafsson; Susanne Rasmussen; Kristian Wachtell; Knut Borch-Johnsen; Hans Ibsen; Torben Jørgensen; Per Hildebrandt Journal: Hypertension Date: 2005-08-29 Impact factor: 10.190
Authors: Rebecca P Gelber; J Michael Gaziano; E John Orav; Joann E Manson; Julie E Buring; Tobias Kurth Journal: J Am Coll Cardiol Date: 2008-08-19 Impact factor: 24.094
Authors: Thomas J Wang; Martin G Larson; Daniel Levy; Emelia J Benjamin; Eric P Leip; Peter W F Wilson; Ramachandran S Vasan Journal: Circulation Date: 2004-02-10 Impact factor: 29.690
Authors: Andrew S Levey; Lesley A Stevens; Christopher H Schmid; Yaping Lucy Zhang; Alejandro F Castro; Harold I Feldman; John W Kusek; Paul Eggers; Frederick Van Lente; Tom Greene; Josef Coresh Journal: Ann Intern Med Date: 2009-05-05 Impact factor: 25.391
Authors: Robert Claus; Dominik Berliner; Udo Bavendiek; Nicolas Vodovar; Ralf Lichtinghagen; Sascha David; Margret Patecki; Jean-Marie Launay; Johann Bauersachs; Hermann Haller; Marcus Hiss; Michael S Balzer Journal: Clin Res Cardiol Date: 2020-01-30 Impact factor: 5.460
Authors: Steffen D Kriechbaum; Lillith Scherwitz; Christoph B Wiedenroth; Felix Rudolph; Jan-Sebastian Wolter; Moritz Haas; Ulrich Fischer-Rasokat; Andreas Rolf; Christian W Hamm; Eckhard Mayer; Stefan Guth; Till Keller; Stavros V Konstantinides; Mareike Lankeit; Christoph Liebetrau Journal: ERJ Open Res Date: 2020-11-02
Authors: Christina Gar; Barbara Thorand; Christian Herder; Chaterina Sujana; Margit Heier; Christa Meisinger; Annette Peters; Wolfgang Koenig; Wolfgang Rathmann; Michael Roden; Michael Stumvoll; Haifa Maalmi; Thomas Meitinger; Holger Then; Jochen Seissler; Cornelia Then Journal: PLoS One Date: 2022-01-06 Impact factor: 3.240
Authors: Susanna Lemmelä; Eleanor M Wigmore; Christian Benner; Aki S Havulinna; Rachel M Y Ong; Tibor Kempf; Kai C Wollert; Stefan Blankenberg; Tanja Zeller; James E Peters; Veikko Salomaa; Maria Fritsch; Ruth March; Aarno Palotie; Mark Daly; Adam S Butterworth; Mervi Kinnunen; Dirk S Paul; Athena Matakidou Journal: Elife Date: 2022-08-02 Impact factor: 8.713