Skip to main content
Top
Published in: Clinical Research in Cardiology 6/2017

01-06-2017 | Original Paper

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

Authors: Christoph Sinning, Francisco Ojeda, Philipp S. Wild, Renate B. Schnabel, Michael Schwarzl, Sevenai Ohdah, Karl J. Lackner, Norbert Pfeiffer, Matthias Michal, Maria Blettner, Thomas Munzel, Tibor Kempf, Kai C. Wollert, Kari Kuulasmaa, Stefan Blankenberg, Veikko Salomaa, Dirk Westermann, Tanja Zeller

Published in: Clinical Research in Cardiology | Issue 6/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. doi:10.1093/eurheartj/ehw128 PubMedCentral Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. doi:10.​1093/​eurheartj/​ehw128 PubMedCentral
3.
go back to reference Baessler A, Strack C, Rousseva E, Wagner F, Bruxmeier J, Schmiedel M, Riegger G, Lahmann C, Loew T, Schmitz G, Fischer M (2012) Growth-differentiation factor-15 improves reclassification for the diagnosis of heart failure with normal ejection fraction in morbid obesity. Eur J Heart Fail 14(11):1240–1248. doi:10.1093/eurjhf/hfs116 CrossRefPubMed Baessler A, Strack C, Rousseva E, Wagner F, Bruxmeier J, Schmiedel M, Riegger G, Lahmann C, Loew T, Schmitz G, Fischer M (2012) Growth-differentiation factor-15 improves reclassification for the diagnosis of heart failure with normal ejection fraction in morbid obesity. Eur J Heart Fail 14(11):1240–1248. doi:10.​1093/​eurjhf/​hfs116 CrossRefPubMed
4.
go back to reference van Hateren KJ, Alkhalaf A, Kleefstra N, Groenier KH, de Jong PE, de Zeeuw D, Gans RO, Struck J, Bilo HJ, Gansevoort RT, Bakker SJ (2012) Comparison of midregional pro-A-type natriuretic peptide and the N-terminal pro-B-type natriuretic peptide for predicting mortality and cardiovascular events. Clin Chem 58(1):293–297. doi:10.1373/clinchem.2011.166348 CrossRefPubMed van Hateren KJ, Alkhalaf A, Kleefstra N, Groenier KH, de Jong PE, de Zeeuw D, Gans RO, Struck J, Bilo HJ, Gansevoort RT, Bakker SJ (2012) Comparison of midregional pro-A-type natriuretic peptide and the N-terminal pro-B-type natriuretic peptide for predicting mortality and cardiovascular events. Clin Chem 58(1):293–297. doi:10.​1373/​clinchem.​2011.​166348 CrossRefPubMed
5.
6.
go back to reference Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K, Borch-Johnsen K, Ibsen H, Jorgensen T, Hildebrandt P (2005) N-terminal pro brain natriuretic peptide is inversely related to metabolic cardiovascular risk factors and the metabolic syndrome. Hypertension 46(4):660–666. doi:10.1161/01.HYP.0000179575.13739.72 CrossRefPubMed Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K, Borch-Johnsen K, Ibsen H, Jorgensen T, Hildebrandt P (2005) N-terminal pro brain natriuretic peptide is inversely related to metabolic cardiovascular risk factors and the metabolic syndrome. Hypertension 46(4):660–666. doi:10.​1161/​01.​HYP.​0000179575.​13739.​72 CrossRefPubMed
7.
go back to reference Krauser DG, Lloyd-Jones DM, Chae CU, Cameron R, Anwaruddin S, Baggish AL, Chen A, Tung R, Januzzi JL Jr (2005) Effect of body mass index on natriuretic peptide levels in patients with acute congestive heart failure: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy. Am Heart J 149(4):744–750. doi:10.1016/j.ahj.2004.07.010 CrossRefPubMed Krauser DG, Lloyd-Jones DM, Chae CU, Cameron R, Anwaruddin S, Baggish AL, Chen A, Tung R, Januzzi JL Jr (2005) Effect of body mass index on natriuretic peptide levels in patients with acute congestive heart failure: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy. Am Heart J 149(4):744–750. doi:10.​1016/​j.​ahj.​2004.​07.​010 CrossRefPubMed
8.
go back to reference Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM, Canham RM, Chung AK, Leonard D, Wians FH Jr, de Lemos JA (2005) Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation 112(14):2163–2168. doi:10.1161/CIRCULATIONAHA.105.555573 CrossRefPubMed Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM, Canham RM, Chung AK, Leonard D, Wians FH Jr, de Lemos JA (2005) Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation 112(14):2163–2168. doi:10.​1161/​CIRCULATIONAHA.​105.​555573 CrossRefPubMed
11.
go back to reference Bayes-Genis A, Lloyd-Jones DM, van Kimmenade RR, Lainchbury JG, Richards AM, Ordonez-Llanos J, Santalo M, Pinto YM, Januzzi JL Jr (2007) Effect of body mass index on diagnostic and prognostic usefulness of amino-terminal pro-brain natriuretic peptide in patients with acute dyspnea. Arch Intern Med 167(4):400–407. doi:10.1001/archinte.167.4.400 CrossRefPubMed Bayes-Genis A, Lloyd-Jones DM, van Kimmenade RR, Lainchbury JG, Richards AM, Ordonez-Llanos J, Santalo M, Pinto YM, Januzzi JL Jr (2007) Effect of body mass index on diagnostic and prognostic usefulness of amino-terminal pro-brain natriuretic peptide in patients with acute dyspnea. Arch Intern Med 167(4):400–407. doi:10.​1001/​archinte.​167.​4.​400 CrossRefPubMed
12.
go back to reference Daniels LB, Clopton P, Bhalla V, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA, Maisel AS (2006) How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study. Am Heart J 151(5):999–1005. doi:10.1016/j.ahj.2005.10.011 CrossRefPubMed Daniels LB, Clopton P, Bhalla V, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA, Maisel AS (2006) How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study. Am Heart J 151(5):999–1005. doi:10.​1016/​j.​ahj.​2005.​10.​011 CrossRefPubMed
13.
go back to reference Ukena C, Kindermann M, Mahfoud F, Geisel J, Lepper PM, Kandolf R, Bohm M, Kindermann I (2014) Diagnostic and prognostic validity of different biomarkers in patients with suspected myocarditis. Clin Res Cardiol 103(9):743–751. doi:10.1007/s00392-014-0709-z CrossRefPubMed Ukena C, Kindermann M, Mahfoud F, Geisel J, Lepper PM, Kandolf R, Bohm M, Kindermann I (2014) Diagnostic and prognostic validity of different biomarkers in patients with suspected myocarditis. Clin Res Cardiol 103(9):743–751. doi:10.​1007/​s00392-014-0709-z CrossRefPubMed
14.
go back to reference Lok DJ, Van Der Meer P, de la Porte PW, Lipsic E, Van Wijngaarden J, Hillege HL, van Veldhuisen DJ (2010) Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study. Clin Res Cardiol 99(5):323–328. doi:10.1007/s00392-010-0125-y CrossRefPubMedPubMedCentral Lok DJ, Van Der Meer P, de la Porte PW, Lipsic E, Van Wijngaarden J, Hillege HL, van Veldhuisen DJ (2010) Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study. Clin Res Cardiol 99(5):323–328. doi:10.​1007/​s00392-010-0125-y CrossRefPubMedPubMedCentral
15.
go back to reference Poss J, Ukena C, Kindermann I, Ehrlich P, Fuernau G, Ewen S, Mahfoud F, Kriechbaum S, Bohm M, Link A (2015) Angiopoietin-2 and outcome in patients with acute decompensated heart failure. Clin Res Cardiol 104(5):380–387. doi:10.1007/s00392-014-0787-y CrossRefPubMed Poss J, Ukena C, Kindermann I, Ehrlich P, Fuernau G, Ewen S, Mahfoud F, Kriechbaum S, Bohm M, Link A (2015) Angiopoietin-2 and outcome in patients with acute decompensated heart failure. Clin Res Cardiol 104(5):380–387. doi:10.​1007/​s00392-014-0787-y CrossRefPubMed
16.
go back to reference Shah RV, Truong QA, Gaggin HK, Pfannkuche J, Hartmann O, Januzzi JL Jr (2012) Mid-regional pro-atrial natriuretic peptide and pro-adrenomedullin testing for the diagnostic and prognostic evaluation of patients with acute dyspnoea. Eur Heart J 33(17):2197–2205. doi:10.1093/eurheartj/ehs136 CrossRefPubMedPubMedCentral Shah RV, Truong QA, Gaggin HK, Pfannkuche J, Hartmann O, Januzzi JL Jr (2012) Mid-regional pro-atrial natriuretic peptide and pro-adrenomedullin testing for the diagnostic and prognostic evaluation of patients with acute dyspnoea. Eur Heart J 33(17):2197–2205. doi:10.​1093/​eurheartj/​ehs136 CrossRefPubMedPubMedCentral
17.
go back to reference Maisel A, Mueller C, Nowak R, Peacock WF, Landsberg JW, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Filippatos GS, Di Somma S, Anand I, Ng L, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Terracciano G, Kremastinos D, Hartmann O, von Haehling S, Bergmann A, Morgenthaler NG, Anker SD (2010) Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol 55(19):2062–2076. doi:10.1016/j.jacc.2010.02.025 CrossRefPubMed Maisel A, Mueller C, Nowak R, Peacock WF, Landsberg JW, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Filippatos GS, Di Somma S, Anand I, Ng L, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Terracciano G, Kremastinos D, Hartmann O, von Haehling S, Bergmann A, Morgenthaler NG, Anker SD (2010) Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol 55(19):2062–2076. doi:10.​1016/​j.​jacc.​2010.​02.​025 CrossRefPubMed
18.
go back to reference Wild PS, Sinning CR, Roth A, Wilde S, Schnabel RB, Lubos E, Zeller T, Keller T, Lackner KJ, Blettner M, Vasan RS, Munzel T, Blankenberg S (2010) Distribution and categorization of left ventricular measurements in the general population: results from the population-based Gutenberg Heart Study. Circ Cardiovasc Imaging 3(5):604–613. doi:10.1161/CIRCIMAGING.109.911933 CrossRefPubMed Wild PS, Sinning CR, Roth A, Wilde S, Schnabel RB, Lubos E, Zeller T, Keller T, Lackner KJ, Blettner M, Vasan RS, Munzel T, Blankenberg S (2010) Distribution and categorization of left ventricular measurements in the general population: results from the population-based Gutenberg Heart Study. Circ Cardiovasc Imaging 3(5):604–613. doi:10.​1161/​CIRCIMAGING.​109.​911933 CrossRefPubMed
20.
go back to reference Schwarzl M, Ojeda F, Zeller T, Seiffert M, Becher PM, Munzel T, Wild PS, Blettner M, Lackner KJ, Pfeiffer N, Beutel ME, Blankenberg S, Westermann D (2016) Risk factors for heart failure are associated with alterations of the LV end-diastolic pressure-volume relationship in non-heart failure individuals: data from a large-scale, population-based cohort. Eur Heart J. doi:10.1093/eurheartj/ehw120 PubMed Schwarzl M, Ojeda F, Zeller T, Seiffert M, Becher PM, Munzel T, Wild PS, Blettner M, Lackner KJ, Pfeiffer N, Beutel ME, Blankenberg S, Westermann D (2016) Risk factors for heart failure are associated with alterations of the LV end-diastolic pressure-volume relationship in non-heart failure individuals: data from a large-scale, population-based cohort. Eur Heart J. doi:10.​1093/​eurheartj/​ehw120 PubMed
21.
go back to reference van Riet EE, Hoes AW, Wagenaar KP, Limburg A, Landman MA, Rutten FH (2016) Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail 18(3):242–252. doi:10.1002/ejhf.483 CrossRefPubMed van Riet EE, Hoes AW, Wagenaar KP, Limburg A, Landman MA, Rutten FH (2016) Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail 18(3):242–252. doi:10.​1002/​ejhf.​483 CrossRefPubMed
22.
go back to reference Wild PS, Zeller T, Beutel M, Blettner M, Dugi KA, Lackner KJ, Pfeiffer N, Munzel T, Blankenberg S (2012) The Gutenberg health study. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 55(6–7):824–829. doi:10.1007/s00103-012-1502-7 CrossRefPubMed Wild PS, Zeller T, Beutel M, Blettner M, Dugi KA, Lackner KJ, Pfeiffer N, Munzel T, Blankenberg S (2012) The Gutenberg health study. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 55(6–7):824–829. doi:10.​1007/​s00103-012-1502-7 CrossRefPubMed
23.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612CrossRefPubMedPubMedCentral
24.
go back to reference Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W (2006) Recommendations for chamber quantification. Eur J Echocardiogr 7(2):79–108. doi:10.1016/j.euje.2005.12.014 CrossRefPubMed Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W (2006) Recommendations for chamber quantification. Eur J Echocardiogr 7(2):79–108. doi:10.​1016/​j.​euje.​2005.​12.​014 CrossRefPubMed
25.
go back to reference Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein G, Drexler H, Johnston N, Wallentin L, Wollert KC (2007) Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem 53(2):284–291. doi:10.1373/clinchem.2006.076828 CrossRefPubMed Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein G, Drexler H, Johnston N, Wallentin L, Wollert KC (2007) Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem 53(2):284–291. doi:10.​1373/​clinchem.​2006.​076828 CrossRefPubMed
28.
go back to reference Borodulin K, Vartiainen E, Peltonen M, Jousilahti P, Juolevi A, Laatikainen T, Mannisto S, Salomaa V, Sundvall J, Puska P (2015) Forty-year trends in cardiovascular risk factors in Finland. Eur J Public Health 25(3):539–546. doi:10.1093/eurpub/cku174 CrossRefPubMed Borodulin K, Vartiainen E, Peltonen M, Jousilahti P, Juolevi A, Laatikainen T, Mannisto S, Salomaa V, Sundvall J, Puska P (2015) Forty-year trends in cardiovascular risk factors in Finland. Eur J Public Health 25(3):539–546. doi:10.​1093/​eurpub/​cku174 CrossRefPubMed
29.
go back to reference DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44(3):837–845CrossRefPubMed DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44(3):837–845CrossRefPubMed
32.
go back to reference Vizzardi E, Sciatti E, Bonadei I, D’Aloia A, Tartiere-Kesri L, Tartiere JM, Cohen-Solal A, Metra M (2015) Effects of spironolactone on ventricular-arterial coupling in patients with chronic systolic heart failure and mild symptoms. Clin Res Cardiol 104(12):1078–1087. doi:10.1007/s00392-015-0877-5 CrossRefPubMed Vizzardi E, Sciatti E, Bonadei I, D’Aloia A, Tartiere-Kesri L, Tartiere JM, Cohen-Solal A, Metra M (2015) Effects of spironolactone on ventricular-arterial coupling in patients with chronic systolic heart failure and mild symptoms. Clin Res Cardiol 104(12):1078–1087. doi:10.​1007/​s00392-015-0877-5 CrossRefPubMed
Metadata
Title
Midregional proadrenomedullin and growth differentiation factor-15 are not influenced by obesity in heart failure patients
Authors
Christoph Sinning
Francisco Ojeda
Philipp S. Wild
Renate B. Schnabel
Michael Schwarzl
Sevenai Ohdah
Karl J. Lackner
Norbert Pfeiffer
Matthias Michal
Maria Blettner
Thomas Munzel
Tibor Kempf
Kai C. Wollert
Kari Kuulasmaa
Stefan Blankenberg
Veikko Salomaa
Dirk Westermann
Tanja Zeller
Publication date
01-06-2017
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 6/2017
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-016-1066-x

Other articles of this Issue 6/2017

Clinical Research in Cardiology 6/2017 Go to the issue