Horm Metab Res 2020; 52(12): 861-868
DOI: 10.1055/a-1212-8759
Endocrine Care

Is There Really an Association of High Circulating Adiponectin Concentration and Mortality or Morbidity Risk in Stable Coronary Artery Disease?

1   2nd Department of Internal Medicine, Faculty of Medicine in Pilsen, Charles University and University Hospital, Pilsen, Czech Republic
2   Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic
,
Jitka Seidlerová
1   2nd Department of Internal Medicine, Faculty of Medicine in Pilsen, Charles University and University Hospital, Pilsen, Czech Republic
2   Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic
,
Jan Bruthans
1   2nd Department of Internal Medicine, Faculty of Medicine in Pilsen, Charles University and University Hospital, Pilsen, Czech Republic
3   Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
,
Julius Gelžinský
1   2nd Department of Internal Medicine, Faculty of Medicine in Pilsen, Charles University and University Hospital, Pilsen, Czech Republic
,
Martina Rychecká
1   2nd Department of Internal Medicine, Faculty of Medicine in Pilsen, Charles University and University Hospital, Pilsen, Czech Republic
,
Markéta Mateřánková
1   2nd Department of Internal Medicine, Faculty of Medicine in Pilsen, Charles University and University Hospital, Pilsen, Czech Republic
2   Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic
,
Petra Karnosová
1   2nd Department of Internal Medicine, Faculty of Medicine in Pilsen, Charles University and University Hospital, Pilsen, Czech Republic
2   Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic
,
Peter Wohlfahrt
3   Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
,
Renata Cífková
3   Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
,
Jan Filipovský
1   2nd Department of Internal Medicine, Faculty of Medicine in Pilsen, Charles University and University Hospital, Pilsen, Czech Republic
2   Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Czech Republic
› Author Affiliations
Funding Information The present analysis was supported by the Health Development Agency of the Czech Ministry of Health (project 17–29520A), Charles University Research Fund (PROGRES, project Q39), and by the Specific Academic Research Project of Charles University (project SVV–2020–2022, No 260 537).

Abstract

Adiponectin has several beneficial properties, namely, on the level of glucose metabolism, but paradoxically, its high concentrations were associated with increased mortality. We aimed to clarify the impact of high serum adiponectin on mortality and morbidity in patients with stable coronary artery heart disease (CAD). A total of 973 patients after myocardial infarction and/or coronary revascularization were followed in a prospective cohort study. All-cause and cardiovascular (CV) death, non-fatal cardiovascular events, and hospitalizations for heart failure (HF) were registered as outcomes. High serum adiponectin levels (≥8.58 ng/ml, i. e., above median) were independently associated with increased risk of 5-year all-cause, CV mortality or HF [with HRR 1.57 (95% CI: 1.07–2.30), 1.74 (95% CI: 1.08–2.81) or 1.94 (95% CI: 1.20–3.12), respectively] when adjusted just for conventional risk factors. However, its significance disappeared if brain natriuretic peptide (BNP) was included in a regression model. In line with this, we observed strong collinearity of adiponectin and BNP. Additionally, major adverse cardiovascular event (i. e., CV death, non-fatal myocardial infarction or stroke, coronary revascularization) incidence risk was not associated with high adiponectin. In conclusion, the observed inverse association between adiponectin concentrations and mortality risk seems to be attributable to concomitantly increased BNP, rather than high adiponectin being a causal factor.



Publication History

Received: 10 May 2020

Accepted after revision: 24 June 2020

Article published online:
03 August 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Scherer PE, Williams S, Fogliano M. et al. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995; 270: 26746-26749
  • 2 Wang ZV, Scherer PE. Adiponectin, the past two decades. J Mol Cell Biol 2016; 8: 93-100
  • 3 Yamauchi T, Kamon J, Ito Y. et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423: 762-769
  • 4 Scarale MG, Fontana A, Trischitta V. et al. Circulating adiponectin levels are paradoxically associated with mortality rate. A systematic review and meta-analysis. J Clin Endocrinol Metab 2018; DOI: 10.1210/jc.2018-01501.
  • 5 Kotseva K, Wood D, De Backer G. et al. EUROASPIRE III: A survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries. Eur J Cardiovasc Prev Rehabil 2009; 16: 121-137
  • 6 Kotseva K, Wood D, De Bacquer D. et al. EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol 2016; 23: 636-648
  • 7 Perk J, De Backer G, Gohlke H. et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012; 33: 1635-1701
  • 8 Konig P, Mayer O, Bruthans J. et al. The prognostic importance of subclinical heart failure in stable coronary heart disease patients. Acta Cardiol 2019; 1-8
  • 9 Nakanishi K, Nishida M, Yamamoto R. et al. Association between N-terminal pro-brain natriuretic peptide and adiponectin in healthy Japanese men. Clin Chim Acta 2016; 460: 138-141
  • 10 Mayer O, Simon J, Plásková M. et al. N-terminal pro B-type natriuretic peptide as prognostic marker for mortality in coronary patients without clinically manifest heart failure. Eur J Epidemiol 2009; 24: 363-368
  • 11 Gardner RS, Ozalp F, Murday AJ. et al. N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure. Eur Heart J 2003; 24: 1735-1743
  • 12 Hartmann F, Packer M, Coats AJ. et al. Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Circulation 2004; 110: 1780-1786
  • 13 Kragelund C, Gronning B, Kober L. et al. N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med 2005; 352: 666-675
  • 14 Wang TJ, Larson MG, Levy D. et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 2004; 350: 655-663
  • 15 Au Yeung SL, Schooling CM. Adiponectin and coronary artery disease risk: A bi-directional Mendelian randomization study. Int J Cardiol 2018; 268: 222-226
  • 16 Borges MC, Lawlor DA, de Oliveira C. et al. Role of adiponectin in coronary heart disease risk: A mendelian randomization study. Circ Res 2016; 119: 491-499
  • 17 Bai W, Huang J, Zhu M. et al. Association between elevated adiponectin level an adverse outcomes in patients with heart failure: a systematic review and meta-analysis. Braz J Med Biol Res 2019; 52: e8416
  • 18 Withers SB, Bussey CE, Saxton SN. et al. Mechanisms of adiponectin-associated perivascular function in vascular disease. Arterioscler Thromb Vasc Biol 2014; 34: 1637-1642
  • 19 Tsukamoto O, Fujita M, Kato M. et al. Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol 2009; 53: 2070-2077
  • 20 Shibata R, Sato K, Pimentel DR. et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med 2005; 11: 1096-1103
  • 21 Shibata R, Ouchi N, Ito M. et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 2004; 10: 1384-1389
  • 22 Dadson K, Turdi S, Hashemi S. et al. Adiponectin is required for cardiac MEF2 activation during pressure overload induced hypertrophy. J Mol Cell Cardiol 2015; 86: 102-109
  • 23 Wang Y, Wang X, Lau WB. et al. Adiponectin inhibits tumor necrosis factor-alpha-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation. Circ Res 2014; 114: 792-805
  • 24 Tao L, Gao E, Jiao X. et al. Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 2007; 115: 1408-1416
  • 25 Shimada K, Miyazaki T, Daida H. Adiponectin and atherosclerotic disease. Clin Chim Acta 2004; 344: 1-12
  • 26 Zhang N, Wei WY, Liao HH. et al. AdipoRon, an adiponectin receptor agonist, attenuates cardiac remodeling induced by pressure overload. J Mol Med (Berl) 2018; 96: 1345-1357