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Obesity cardiomyopathy: pathogenesis and pathophysiology

Abstract

Obesity is becoming a worldwide phenomenon. Myocardial changes associated with the obese state are increasingly recognized, independent of hypertension, obstructive sleep apnea and coronary artery disease. The existence of a cardiomyopathy of obesity is supported by a range of evidence: epidemiologic study findings, which have shown an association between obesity and heart failure; clinical studies that have confirmed the association of adiposity with left ventricular dysfunction, independent of hypertension, coronary artery disease and other heart disease; and experimental evidence of structural and functional changes in the myocardium in response to increased adiposity. The most important mechanisms in the development of obesity cardiomyopathy are metabolic disturbances (insulin resistance, increased free fatty acid levels, and also increased levels of adipokines), activation of the renin–angiotensin–aldosterone and sympathetic nervous systems, myocardial remodeling, and small-vessel disease (both microangiopathy and endothelial dysfunction). In the first part of this two-part Review, we seek to evaluate the emerging evidence for the existence of a cardiomyopathy of obesity and clarify the responsible mechanisms.

Key Points

  • The existence of a cardiomyopathy of obesity is increasingly recognized and supported by many experimental models and epidemiological and clinical studies

  • These myocardial changes cannot be ascribed to hypertension, diabetes, obstructive sleep apnea or coronary artery disease

  • Obesity cardiomyopathy involves both left and right ventricular structure, and systolic and diastolic function

  • Metabolic factors (insulin resistance, lipotoxicity, increased free fatty acids, and adipokines), renin–angiotensin–aldosterone and sympathetic nervous systems, myocardial remodeling and small vessel disease can all contribute

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Figure 1: Clinical studies using tissue Doppler imaging to demonstrate relationship of excess weight with (A) left ventricular systolic function (LV sm),25 (B) left ventricular diastolic function (LV em),25 and (C) right ventricular diastolic function (RV em)22

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References

  1. Allison DB et al. (1999) Annual deaths attributable to obesity in the United States. JAMA 282: 1530–1538

    Article  CAS  Google Scholar 

  2. Duflou J et al. (1995) Sudden death as a result of heart disease in morbid obesity. Am Heart J 130: 306–313

    Article  CAS  Google Scholar 

  3. Kasper EK et al. (1992) Cardiomyopathy of obesity: a clinicopathologic evaluation of 43 obese patients with heart failure. Am J Cardiol 70: 921–924

    Article  CAS  Google Scholar 

  4. Smith HL and Willius FA (1973) Adiposity of the heart. Arch Intern Med 52: 911–931

    Article  Google Scholar 

  5. Warnes CA and Roberts WC (1984) The heart in massive (more than 300 pounds or 136 kilograms) obesity: analysis of 12 patients studied at necropsy. Am J Cardiol 54: 1087–1091

    Article  CAS  Google Scholar 

  6. Hubert HB et al. (1983) Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 67: 968–977

    Article  CAS  Google Scholar 

  7. Chen YT et al. (1999) Risk factors for heart failure in the elderly: a prospective community-based study. Am J Med 106: 605–612

    Article  CAS  Google Scholar 

  8. Dagenais GR et al. (2005) Prognostic impact of body weight and abdominal obesity in women and men with cardiovascular disease. Am Heart J 149: 54–60

    Article  Google Scholar 

  9. Dwyer EM et al. (2000) Role of hypertension, diabetes, obesity, and race in the development of symptomatic myocardial dysfunction in a predominantly minority population with normal coronary arteries. Am Heart J 139: 297–304

    Article  CAS  Google Scholar 

  10. He J et al. (2001) Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 161: 996–1002

    Article  CAS  Google Scholar 

  11. Kenchaiah S et al. (2002) Obesity and the risk of heart failure. N Engl J Med 347: 305–313

    Article  Google Scholar 

  12. Murphy NF et al. (2006) Long-term cardiovascular consequences of obesity: 20-year follow-up of more than 15,000 middle-aged men and women (the Renfrew-Paisley study). Eur Heart J 27: 96–106

    Article  CAS  Google Scholar 

  13. Fischer M et al. (2001) Prevalence of left ventricular diastolic dysfunction in the general population [abstract]. Circulation 104: I1–108

    Article  Google Scholar 

  14. Karason et al. (1997) Effects of obesity and weight loss on left ventricular mass and relative wall thickness: survey and intervention study. BMJ 315: 912–916

    Article  CAS  Google Scholar 

  15. Amad KH et al. (1965) The cardiac pathology of chronic exogenous obesity. Circulation 32: 740–745

    Article  CAS  Google Scholar 

  16. Lauer MS et al. (1991) The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study. JAMA 266: 231–236

    Article  CAS  Google Scholar 

  17. Nakajima T et al. (1985) Noninvasive study of left ventricular performance in obese patients: influence of duration of obesity. Circulation 71: 481–486

    Article  CAS  Google Scholar 

  18. Alaud-din A et al. (1990) Assessment of cardiac function in patients who were morbidly obese. Surgery 108: 809–818

    CAS  PubMed  Google Scholar 

  19. de Simone G et al. (1994) Relation of obesity and gender to left ventricular hypertrophy in normotensive and hypertensive adults. Hypertension 23: 600–606

    Article  CAS  Google Scholar 

  20. Wong CY et al. (2006) Association of subclinical right ventricular dysfunction with obesity. J Am Coll Cardiol 47: 611–616

    Article  Google Scholar 

  21. Cittadini A et al. (1999) Cardiovascular abnormalities in transgenic mice with reduced brown fat: an animal model of human obesity. Circulation 100: 2177–2183

    Article  CAS  Google Scholar 

  22. Mizushige K et al. (2000) Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model. Circulation 101: 899–907

    Article  CAS  Google Scholar 

  23. Wong CY et al. (2004) Alterations of left ventricular myocardial characteristics associated with obesity. Circulation 110: 3081–3087

    Article  Google Scholar 

  24. de Divitiis O et al. (1981) Obesity and cardiac function. Circulation 64: 477–482

    Article  CAS  Google Scholar 

  25. Ku CS et al. (1994) Left ventricular filling in young normotensive obese adults. Am J Cardiol 73: 613–615

    Article  CAS  Google Scholar 

  26. Crisostomo LL et al. (1999) Comparison of left ventricular mass and function in obese versus nonobese women <40 years of age. Am J Cardiol 84: 1127–1129

    Article  CAS  Google Scholar 

  27. Pascual M et al. (2003) Effects of isolated obesity on systolic and diastolic left ventricular function. Heart 89: 1152–1156

    Article  CAS  Google Scholar 

  28. Peterson LR et al. (2004) Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging. J Am Coll Cardiol 43: 1399–1404

    Article  Google Scholar 

  29. Ferraro S et al. (1996) Left ventricular systolic and diastolic function in severe obesity: a radionuclide study. Cardiology 87: 347–353

    Article  CAS  Google Scholar 

  30. Ahmed Q et al. (1997) Cardiopulmonary pathology in patients with sleep apnea/obesity hypoventilation syndrome. Hum Pathol 28: 264–269

    Article  CAS  Google Scholar 

  31. Alpert MA (2001) Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci 321: 225–236

    Article  CAS  Google Scholar 

  32. Marshall JD et al. (2005) New Alstrom syndrome phenotypes based on the evaluation of 182 cases. Arch Intern Med 165: 675–683

    Article  Google Scholar 

  33. Peterson LR et al. (2004) Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 109: 2191–2196

    Article  Google Scholar 

  34. Katz EB et al. (1995) Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature 377: 151–155

    Article  CAS  Google Scholar 

  35. Chiu HC et al. (2001) A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest 107: 813–822

    Article  CAS  Google Scholar 

  36. Zhou YT et al. (2000) Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci USA 97: 1784–1789

    Article  CAS  Google Scholar 

  37. Cittadini A et al. (1996) Differential cardiac effects of growth hormone and insulin-like growth factor-1 in the rat: a combined in vivo and in vitro evaluation. Circulation 93: 800–809

    Article  CAS  Google Scholar 

  38. Listenberger LL and Schaffer JE (2002) Mechanisms of lipoapoptosis: implications for human heart disease. Trends Cardiovasc Med 12: 134–138

    Article  CAS  Google Scholar 

  39. McGavock JM et al. (2006) Adiposity of the heart, revisited. Ann Intern Med 144: 517–524

    Article  CAS  Google Scholar 

  40. Nickola MW et al. (2000) Leptin attenuates cardiac contraction in rat ventricular myocytes: role of NO. Hypertension 36: 501–505

    Article  CAS  Google Scholar 

  41. Minhas KM et al. (2005) Leptin repletion restores depressed β-adrenergic contractility in ob/ob mice independently of cardiac hypertrophy. J Physiol 565: 463–474

    Article  CAS  Google Scholar 

  42. Haynes WG et al. (1997) Sympathetic and cardiorenal actions of leptin. Hypertension 30: 619–623

    Article  CAS  Google Scholar 

  43. Shibata R et al. (2004) Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 10: 1384–1389

    Article  CAS  Google Scholar 

  44. Maeda N et al. (2001) PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50: 2094–2099

    Article  CAS  Google Scholar 

  45. Hotamisligil GS et al. (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259: 87–91

    Article  CAS  Google Scholar 

  46. Xu H et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821–1830

    Article  CAS  Google Scholar 

  47. Giacchetti G et al. (2002) Overexpression of the renin–angiotensin system in human visceral adipose tissue in normal and overweight subjects. Am J Hypertens 15: 381–388

    Article  CAS  Google Scholar 

  48. Goodfriend et al. (1999) Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women. Obes Res 7: 355–362

    Article  CAS  Google Scholar 

  49. Lijnen P and Petrov V (1999) Antagonism of the renin–angiotensin system, hypertrophy and gene expression in cardiac myocytes. Methods Find Exp Clin Pharmacol 21: 363–374

    Article  CAS  Google Scholar 

  50. Brilla CG et al. (1993) Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol 25: 563–575

    Article  CAS  Google Scholar 

  51. Harte A et al. (2005) Insulin-mediated upregulation of the renin angiotensin system in human subcutaneous adipocytes is reduced by rosiglitazone. Circulation 111: 1954–1961

    Article  CAS  Google Scholar 

  52. Festa A et al. (2000) Heart rate in relation to insulin sensitivity and insulin secretion in nondiabetic subjects. Diabetes Care 23: 624–628

    Article  CAS  Google Scholar 

  53. de Jongh RT et al. (2004) Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance. Circulation 109: 2529–2535

    Article  Google Scholar 

  54. Yudkin JS et al. (2005) “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 365: 1817–1820

    Article  Google Scholar 

  55. Sundell J et al. (2002) Obesity affects myocardial vasoreactivity and coronary flow response to insulin. Obes Res 10: 617–624

    Article  CAS  Google Scholar 

  56. McCrohon JA et al. (2003) Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Circulation 108: 54–59

    Article  CAS  Google Scholar 

  57. Thakur V et al. (2001) Obesity, hypertension, and the heart. Am J Med Sci 321: 242–248

    Article  CAS  Google Scholar 

  58. Laaban JP et al. (2002) Left ventricular systolic dysfunction in patients with obstructive sleep apnea syndrome. Chest 122: 1133–1138

    Article  Google Scholar 

  59. Grassi G et al. (2005) Obstructive sleep apnea-dependent and -independent adrenergic activation in obesity. Hypertension 46: 321–325

    Article  CAS  Google Scholar 

  60. Alpert MA et al. (1995) Relation of duration of morbid obesity to left ventricular mass, systolic function, and diastolic filling, and effect of weight loss. Am J Cardiol 76: 1194–1197

    Article  CAS  Google Scholar 

  61. Licata G et al. (1992) Left ventricular function response to exercise in normotensive obese subjects: influence of degree and duration of obesity. Int J Cardiol 37: 223–230

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the support of the National Health and Medical Research Council, Canberra, Australia (Centers of Clinical Research Excellence Award and postgraduate research scholarship).

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Correspondence to Thomas H Marwick.

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Competing interests

C Wong declared he has no competing interests.

TH Marwick receives grant support from GE Healthcare and Philips Medical Systems, but unrelated to this topic.

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Wong, C., Marwick, T. Obesity cardiomyopathy: pathogenesis and pathophysiology. Nat Rev Cardiol 4, 436–443 (2007). https://doi.org/10.1038/ncpcardio0943

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