Obesity Research & Clinical Practice (2012) 6, e181—e188
REVIEW
A perspective on obesity cardiomyopathy Tendoh Timoh a,1, Michelle E. Bloom b,1, Robert R. Siegel c, Gabriel Wagman d, Gregg M. Lanier e, Timothy J. Vittorio d,∗ a
Department of Internal Medicine, Mount Sinai School of Medicine, New York, NY, United States Division of Cardiology, State University of New York at Stony Brook, Stony Brook, NY, United States c Division of Cardiology, Albert Einstein College of Medicine, Bronx Municipal Hospital Center, Bronx, NY, United States d St. Francis Hospital — The Heart Center, Division of Cardiology, Center of Advanced Cardiac Therapeutics, Roslyn, NY 11576-1348, United States e Division of Cardiology, New York Medical College, Westchester Medical Center, Valhalla, NY, United States b
Received 13 December 2011 ; received in revised form 22 February 2012; accepted 22 February 2012
KEYWORDS Bariatric surgery; Cardiomyopathy; Heart failure; Lipotoxic; Mechanical circulatory support devices
Summary Obesity is a major health concern worldwide as obese individuals have a greater risk of death from any cause than normal-weight individuals. As the number of overweight children and adolescents continues to rise, so too has the scope of the obesity epidemic grown substantially. In this article, the authors discuss the role of obesity in the development of heart failure and the pathophysiology of obesity cardiomyopathy, as well as explore the potential role of bariatric surgery and mechanical circulatory support devices (MCSD) as potential therapeutic targets. © 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
Contents Introduction ............................................................................................... Obesity and heart failure .................................................................................. Pathophysiology of obesity cardiomyopathy (OCM) ......................................................... Lipotoxic cardiomyopathy ................................................................................. Neurohumoral overactivation .............................................................................. Prevention/lifestyle modification .......................................................................... Obesity — role of bariatric surgery.........................................................................
∗ 1
Corresponding author. Tel.: +1 516 562 2092; fax: +1 516 562 2094. E-mail address: t [email protected] (T.J. Vittorio). These authors contributed equally to this manuscript.
1871-403X/$ — see front matter © 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.orcp.2012.02.011
e182 e182 e182 e183 e183 e183 e185
e182
T. Timoh et al.
Reverse remodeling........................................................................................ Mortality — the ‘‘obesity paradox’’ ........................................................................ The potential role for mechanical circulatory support devices as bridge to transplantation or destination therapy........................................................................................ Conclusion................................................................................................. Conflicts of interest ....................................................................................... Acknowledgements ........................................................................................ References ................................................................................................
Introduction Obesity is a major health concern in the United States and worldwide with at least 300 million obese adults (Body mass index [BMI] > 30 kg/m2 ) and over one billion overweight adults (BMI 25—29.9 kg/m2 ) [1,2]. Obese individuals have a 50—100% greater risk of death from any cause than normal-weight individuals [2]. Based on data compilated from national statistics including prospective cohort and published studies, the estimated number of annual deaths attributable to obesity among US adults is approximately 280,000 based on hazard ratios from all subjects and 325,000 based on hazard ratios from only nonsmokers and never-smokers [3]. As the number of overweight children and adolescents having doubled and tripled respectively since 1980 [2,4], the scope of the obesity epidemic has grown substantially.
Obesity and heart failure Reports of an association between obesity and heart failure (HF) date back as far as the 1930s. In the 1990s Kasper et al. [5] reported a higher incidence of idiopathic, dilated cardiomyopathy [IDCM] in obese patients (average body weight of 130 kg), compared with lean patients (average body weight of 71 kg) (76.7% versus 35.5%, p < 0.0001). A landmark epidemiological study by Kenchaiah et al. [6] in 2002 reported that the population attributable risk for HF caused by obesity was 13.9% in women and 10.9% in men. After controlling for other risk factors, every one increment in BMI increases the risk of HF by 5% in men and 7% in women [2,5]. After adjustment of other known risk factors such as hypertension, coronary artery disease and diabetes mellitus, obesity still remains an independent risk factor for left ventricular (LV) dysfunction [2]. The Framingham Heart Study identified obesity as a major risk factor for HF in both men and women, with excessive body weight adversely affecting ventricular function [2,7]. Visceral fat, duration of
e185 e186 e186 e187 e187 e187 e187
obesity and increased age were all found to be important risk factors for development of obesity related heart dysfunction [2]. Alpert et al. [8,9] report the duration of morbid obesity (BMI > 35 kg/m2 ) as one of the strongest predictors of HF among obese persons — the probability of developing HF is 66% with 20 years of obesity and 93% with 25 years of obesity. Obesity cardiomyopathy, otherwise referred to as ‘‘lipotoxic cardiomyopathy’’ is now being increasingly recognized in the HF community.
Pathophysiology of obesity cardiomyopathy (OCM) OCM presents with a similar clinical spectrum of HF symptoms as cardiomyopathies of other etiologies. Clinical symptoms include dyspnea, orthopnea, paroxysmal nocturnal dyspnea, wheezing, exercise intolerance and lower extremity edema [2]. These symptoms have been attributed to mechanical consequences of structural remodeling of the heart [2,3,5—10]. Ventricular remodeling is thought to be related to the direct toxic effects of excess adipose tissue which may be potentiated by insulin-resistance, cardiac steatosis and neurohumoral overactivation, in particular, the renin—angiotensin—aldosterone and sympathetic nervous systems. Additionally, pulmonary hypertension as a result of hypoxemia from obstructive sleep apnea syndrome (OSAS) and/or obesityhypoventilation syndrome (OHS/Pickwickian syndrome) [2,3,5—8] likely plays a role. Structural heart changes related to obesity include increased LV wall thickening (both eccentric and concentric), increased LV mass and LV dilatation [2,9,10]. The evaluation of right ventricular (RV) dysfunction in obese patients is challenging due to the high comorbid rate of OSAS and pulmonary hypertension, however an independent association between obesity and RV dysfunction has been described. Alpert and colleagues [8,9,11,12] described increased RV wall thickening and volume in obese patients. In normotensive morbidly obese
A perspective on obesity cardiomyopathy Table 1 Factors associated with HF in morbidly obese patients. Factor
P-value
Duration of morbid obesity Left ventricular (LV) internal dimension in diastole LV end-systolic wall stress Left atrial dimension Right ventricular (RV) internal dimension
35 kg/m2 ) had an elevated risk of post-operative mortality and failure of procedural success. We postulate that MCSDs such as the LVAD might be an attractive target as destination therapy or bridge to transplantation in morbidly obese patients, however further RCTs are necessary to delineate patient criteria.
Conclusion As the obesity epidemic continues to rise in tremendous proportion, there will be a growing need for advanced HF therapies in this population of patients. While data is sparse, there is certainly evidence to suggest that weight reduction surgery may confer a mechanism of ‘‘reverse remodeling’’ and subsequent clinical improvement. In patients with the most advanced disease, LVADs are an attractive target either as a bridge to ventricular recovery with subsequent weight reduction surgery, or as destination therapy in those who otherwise would be excluded from orthotopic heart transplantation. There is a critical need for further studies to determine whether such therapies could be utilized safely and effectively. If these improvements in the cardiac profile are seen post-bariatric surgery, then is this enough clinical evidence for a therapeutic strategy that utilizes this model, vis-à-vis ‘‘rescue bariatric surgery,’’ and more importantly as a ‘‘bridge to transplantation.’’
Conflicts of interest The authors have no financial disclosures.
e187
Acknowledgements None.
References [1] Waxman A. Prevention of chronic diseases: WHO global strategy on diet, physical activity and health. Food Nutr Bull 2003;24:281—4. [2] Dela Cruz CS, Matthay RA. Role of obesity in cardiomyopathy and pulmonary hypertension. Clin Chest Med 2009;30:509—23, ix. [3] Allison D, Fontaine KR, Manson JE, Stevens J, Vanltallie TB. Annual deaths attributable to obesity in the United States. JAMA 1999;282(16):1530—8. [4] Smith HWF. Adiposity of the heart: a clinical and pathologic study of one hundred and thirty-six obese patients. Arch Intern Med 1933;52:911—31. [5] Kasper EK, Hruban RH, Baughman KL. Cardiomyopathy of obesity: a clinicopathologic evaluation of 43 obese patients with heart failure. Am J Cardiol 1992;70:921—4. [6] Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, et al. Obesity and the risk of heart failure. N Engl J Med 2002;347:305—13. [7] Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968—77. [8] Alpert MA, Terry BE, Mulekar M, Cohen MV, Massey CV, Fan TM, et al. Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss. Am J Cardiol 1997;80:736—40. [9] Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci 2001;321:225—36. [10] Huffman C, Wagman G, Fudim M, Zolty R, Vittorio T. Reversible cardiomyopathies — a review. Transplant Proc 2010;42:3673—8. [11] Alpert MA, Fraley MA, Birchem JA, Senkottaiyan N. Management of obesity cardiomyopathy. Expert Rev Cardiovasc Ther 2005;3:225—30. [12] Alpert MA, Lambert CR, Terry BE, Cohen MV, Mukerji V, Massey CV, et al. Influence of left ventricular mass on left ventricular diastolic filling in normotensive morbid obesity. Am Heart J 1995;130:1068—73. [13] Powell BD, Redfield MM, Bybee KA, Freeman WK, Rihal CS. Association of obesity with left ventricular remodeling and diastolic dysfunction in patients without coronary artery disease. Am J Cardiol 2006;98:116—20. [14] Lavie CJ, Messerli FH. Cardiovascular adaptation to obesity and hypertension. Chest 1986;90:275—9. [15] Alexander JK. Obesity and the heart. Heart Dis Stroke 1993;2:317—21. [16] Listenberger LL, Schaffer JE. Mechanisms of lipoapoptosis: implications for human heart disease. Trends Cardiovasc Med 2002;12:134—8. [17] Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A 2000;97:1784—9. [18] Banerjee S, Peterson LR. Myocardial metabolism and cardiac performance in obesity and insulin resistance. Curr Cardiol Rep 2007;9:143—9.
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[19] Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 2004;109:2191—6. [20] McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. Ann Intern Med 2006;144:517—24. [21] Shibata R, Ouchi N, Ito M, Kihara S, Shiojima P, Pimentel DR, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 2004;10:1384—9. [22] Harte A, McTernan P, Chetty R, Coppack S, Katz J, Smith S, et al. Insulin-mediated upregulation of the renin angiotensin system in human subcutaneous adipocytes is reduced by rosiglitazone. Circulation 2005;111:1954—61. [23] Hamdy O. Lifestyle modification and endothelial function in obese subjects. Expert Rev Cardiovasc Ther 2005;3(2):231—41. [24] Knowler KC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EH, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346(6):393—403. [25] Thörne A, Lönnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 2002;26(2): 193—9. [26] Miyatake N, Takahashi K, Wada J, Nishikawa H, Morishita A, Suzuki H, et al. Daily exercise lowers blood pressure and reduces visceral adipose tissue areas in overweight Japanese men. Diabetes Res Clin Pract 2003;62(3):149—57. [27] Alexander JK. Appendix. In: Alpert MA, Alexander JK, editors. The Heart and Lung in Obesity. NY, USA: Futura Publishing; 1998. p. 239—43. [28] Mehra MR, Kobashigawa J, Starling R, Russell S, Uber PA, Parameshwar J, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates — 2006. J Heart Lung Transplant 2006;25:1024—42. [29] Alsabrook GD, Goodman HR, Alexander JW. Gastric bypass for morbidly obese patients with established cardiac disease. Obes Surg 2006;16:1272—7. [30] Ashrafian H, le Roux CW, Darzi A, Athanasiou T. Effects of bariatric surgery on cardiovascular function. Circulation 2008;118:2091—102. [31] Reigle J. Heart failure, obesity and bariatric surgery. Prog Cardiovasc Nurs 2009;24:36—8. [32] Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc 2005;80:1157—62. [33] McCloskey CA, Ramani GV, Mathier MA, Schauer PR, Eid GM, Mattar SG, et al. Bariatric surgery improves cardiac function in morbidly obese patients with severe cardiomyopathy. Surg Obes Relat Dis 2007;3:503—7.
[34] Lakhani M, Fein S. Effects of obesity and subsequent weight reduction on left ventricular function. Cardiol Rev 2011;19:1—4. [35] Alpert MA, Lambert CR, Panayiotou H, Terry BE, Cohen MV, Massey CV, et al. Relation of duration of morbid obesity to left ventricular mass, systolic function, and diastolic filling, and effect of weight loss. Am J Cardiol 1995;76:1194—7. [36] Willens HJ, Byers P, Chirinos JA, Labrador E, Hare JM, de Marchena E. Effects of weight loss after bariatric surgery on epicardial fat measured using echocardiography. Am J Cardiol 2007;99:1242—5. [37] Ristow B, Rabkin J, Haeusslein E. Improvement in dilated cardiomyopathy after bariatric surgery. J Card Fail 2008;14:198—202. [38] Iyengar S, Leier CV. Rescue bariatric surgery for obesityinduced cardiomyopathy. Am J Med 2006;119:e5—6. [39] Kenchaiah S, Pocock SJ, Wang D, Finn PV, Zornoff LA, Skali H, et al. Body mass index and prognosis in patients with chronic heart failure: insights from the Candesartan in Heart Failure Failure: assessment of Reduction in Mortality and Morbidity (CHARM) Program. Circulation 2007;116:627—36. [40] Gustafsson F, Kragelund CB, Torp-Pedersen C, Seibaek M, Burchardt H, Akkan D, et al. Effect of obesity and being overweigth on long-term mortality in congestive heart failure: influence of left ventricualr systolic function. Eur Heart J 2005;26:58—64. [41] Curtis JP, Selter JG, Wang Y, Rathore SS, Jovin IS, Jadbabaie F, et al. The obesity paradox: body mass index and outcomes in patients with heart failure. Arch Intern Med 2005;165:55—61. [42] Watanabe S, Tamura T, Ono K, Horiuchi H, Kimura T, Kita T, et al. Insulin-like growth factor axis (insulin-like growth factor-I/insulin-like growth factor-binding protein3) as a prognostic predictor of heart failure: association with adiponectin. Eur J Heart Fail 2010;12:1214—22. [43] Frankenstein L, Zugck C, Nelles M, Schellberg D, Katus HA, Remppis BA. The obesity paradox in stable chronic heart failure does not persist after matching for indicators of disease severity and confounders. Eur J Heart Fail 2009;11:1189—94. [44] Kamdar KL, Martinez F, Colvin-Adams M, Boyle A, Joyce L, John R. Obesity — no longer an exclusion criteria for LVAD implantation. J Heart Lung Transplant 2009:28:S82 [Abstract]. [45] Butler J, Howser R, Portner PM, Pierson 3rd RN. Body mass index and outcomes after left ventricular assist device placement. Ann Thorac Surg 2005;79:66—73. [46] Coyle LA, Ising MS, Gallagher C, Bhat G, Kurlen S, Sobieski MA, et al. Destination therapy: one-year outcomes in patients with a body mass index greater than 30. Artif Organs 2010;34:93—7. [47] Musci M, Loforte A, Potapov EV, Krabatsch T, Weng Y, Pasic M, et al. Body mass index and outcome after ventricular assist device placement. Ann Thorac Surg 2008;86:1236—42.
Available online at www.sciencedirect.com
REVIEW
A perspective on obesity cardiomyopathy Tendoh Timoh a,1, Michelle E. Bloom b,1, Robert R. Siegel c, Gabriel Wagman d, Gregg M. Lanier e, Timothy J. Vittorio d,∗ a
Department of Internal Medicine, Mount Sinai School of Medicine, New York, NY, United States Division of Cardiology, State University of New York at Stony Brook, Stony Brook, NY, United States c Division of Cardiology, Albert Einstein College of Medicine, Bronx Municipal Hospital Center, Bronx, NY, United States d St. Francis Hospital — The Heart Center, Division of Cardiology, Center of Advanced Cardiac Therapeutics, Roslyn, NY 11576-1348, United States e Division of Cardiology, New York Medical College, Westchester Medical Center, Valhalla, NY, United States b
Received 13 December 2011 ; received in revised form 22 February 2012; accepted 22 February 2012
KEYWORDS Bariatric surgery; Cardiomyopathy; Heart failure; Lipotoxic; Mechanical circulatory support devices
Summary Obesity is a major health concern worldwide as obese individuals have a greater risk of death from any cause than normal-weight individuals. As the number of overweight children and adolescents continues to rise, so too has the scope of the obesity epidemic grown substantially. In this article, the authors discuss the role of obesity in the development of heart failure and the pathophysiology of obesity cardiomyopathy, as well as explore the potential role of bariatric surgery and mechanical circulatory support devices (MCSD) as potential therapeutic targets. © 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
Contents Introduction ............................................................................................... Obesity and heart failure .................................................................................. Pathophysiology of obesity cardiomyopathy (OCM) ......................................................... Lipotoxic cardiomyopathy ................................................................................. Neurohumoral overactivation .............................................................................. Prevention/lifestyle modification .......................................................................... Obesity — role of bariatric surgery.........................................................................
∗ 1
Corresponding author. Tel.: +1 516 562 2092; fax: +1 516 562 2094. E-mail address: t [email protected] (T.J. Vittorio). These authors contributed equally to this manuscript.
1871-403X/$ — see front matter © 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.orcp.2012.02.011
e182 e182 e182 e183 e183 e183 e185
e182
T. Timoh et al.
Reverse remodeling........................................................................................ Mortality — the ‘‘obesity paradox’’ ........................................................................ The potential role for mechanical circulatory support devices as bridge to transplantation or destination therapy........................................................................................ Conclusion................................................................................................. Conflicts of interest ....................................................................................... Acknowledgements ........................................................................................ References ................................................................................................
Introduction Obesity is a major health concern in the United States and worldwide with at least 300 million obese adults (Body mass index [BMI] > 30 kg/m2 ) and over one billion overweight adults (BMI 25—29.9 kg/m2 ) [1,2]. Obese individuals have a 50—100% greater risk of death from any cause than normal-weight individuals [2]. Based on data compilated from national statistics including prospective cohort and published studies, the estimated number of annual deaths attributable to obesity among US adults is approximately 280,000 based on hazard ratios from all subjects and 325,000 based on hazard ratios from only nonsmokers and never-smokers [3]. As the number of overweight children and adolescents having doubled and tripled respectively since 1980 [2,4], the scope of the obesity epidemic has grown substantially.
Obesity and heart failure Reports of an association between obesity and heart failure (HF) date back as far as the 1930s. In the 1990s Kasper et al. [5] reported a higher incidence of idiopathic, dilated cardiomyopathy [IDCM] in obese patients (average body weight of 130 kg), compared with lean patients (average body weight of 71 kg) (76.7% versus 35.5%, p < 0.0001). A landmark epidemiological study by Kenchaiah et al. [6] in 2002 reported that the population attributable risk for HF caused by obesity was 13.9% in women and 10.9% in men. After controlling for other risk factors, every one increment in BMI increases the risk of HF by 5% in men and 7% in women [2,5]. After adjustment of other known risk factors such as hypertension, coronary artery disease and diabetes mellitus, obesity still remains an independent risk factor for left ventricular (LV) dysfunction [2]. The Framingham Heart Study identified obesity as a major risk factor for HF in both men and women, with excessive body weight adversely affecting ventricular function [2,7]. Visceral fat, duration of
e185 e186 e186 e187 e187 e187 e187
obesity and increased age were all found to be important risk factors for development of obesity related heart dysfunction [2]. Alpert et al. [8,9] report the duration of morbid obesity (BMI > 35 kg/m2 ) as one of the strongest predictors of HF among obese persons — the probability of developing HF is 66% with 20 years of obesity and 93% with 25 years of obesity. Obesity cardiomyopathy, otherwise referred to as ‘‘lipotoxic cardiomyopathy’’ is now being increasingly recognized in the HF community.
Pathophysiology of obesity cardiomyopathy (OCM) OCM presents with a similar clinical spectrum of HF symptoms as cardiomyopathies of other etiologies. Clinical symptoms include dyspnea, orthopnea, paroxysmal nocturnal dyspnea, wheezing, exercise intolerance and lower extremity edema [2]. These symptoms have been attributed to mechanical consequences of structural remodeling of the heart [2,3,5—10]. Ventricular remodeling is thought to be related to the direct toxic effects of excess adipose tissue which may be potentiated by insulin-resistance, cardiac steatosis and neurohumoral overactivation, in particular, the renin—angiotensin—aldosterone and sympathetic nervous systems. Additionally, pulmonary hypertension as a result of hypoxemia from obstructive sleep apnea syndrome (OSAS) and/or obesityhypoventilation syndrome (OHS/Pickwickian syndrome) [2,3,5—8] likely plays a role. Structural heart changes related to obesity include increased LV wall thickening (both eccentric and concentric), increased LV mass and LV dilatation [2,9,10]. The evaluation of right ventricular (RV) dysfunction in obese patients is challenging due to the high comorbid rate of OSAS and pulmonary hypertension, however an independent association between obesity and RV dysfunction has been described. Alpert and colleagues [8,9,11,12] described increased RV wall thickening and volume in obese patients. In normotensive morbidly obese
A perspective on obesity cardiomyopathy Table 1 Factors associated with HF in morbidly obese patients. Factor
P-value
Duration of morbid obesity Left ventricular (LV) internal dimension in diastole LV end-systolic wall stress Left atrial dimension Right ventricular (RV) internal dimension
35 kg/m2 ) had an elevated risk of post-operative mortality and failure of procedural success. We postulate that MCSDs such as the LVAD might be an attractive target as destination therapy or bridge to transplantation in morbidly obese patients, however further RCTs are necessary to delineate patient criteria.
Conclusion As the obesity epidemic continues to rise in tremendous proportion, there will be a growing need for advanced HF therapies in this population of patients. While data is sparse, there is certainly evidence to suggest that weight reduction surgery may confer a mechanism of ‘‘reverse remodeling’’ and subsequent clinical improvement. In patients with the most advanced disease, LVADs are an attractive target either as a bridge to ventricular recovery with subsequent weight reduction surgery, or as destination therapy in those who otherwise would be excluded from orthotopic heart transplantation. There is a critical need for further studies to determine whether such therapies could be utilized safely and effectively. If these improvements in the cardiac profile are seen post-bariatric surgery, then is this enough clinical evidence for a therapeutic strategy that utilizes this model, vis-à-vis ‘‘rescue bariatric surgery,’’ and more importantly as a ‘‘bridge to transplantation.’’
Conflicts of interest The authors have no financial disclosures.
e187
Acknowledgements None.
References [1] Waxman A. Prevention of chronic diseases: WHO global strategy on diet, physical activity and health. Food Nutr Bull 2003;24:281—4. [2] Dela Cruz CS, Matthay RA. Role of obesity in cardiomyopathy and pulmonary hypertension. Clin Chest Med 2009;30:509—23, ix. [3] Allison D, Fontaine KR, Manson JE, Stevens J, Vanltallie TB. Annual deaths attributable to obesity in the United States. JAMA 1999;282(16):1530—8. [4] Smith HWF. Adiposity of the heart: a clinical and pathologic study of one hundred and thirty-six obese patients. Arch Intern Med 1933;52:911—31. [5] Kasper EK, Hruban RH, Baughman KL. Cardiomyopathy of obesity: a clinicopathologic evaluation of 43 obese patients with heart failure. Am J Cardiol 1992;70:921—4. [6] Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, et al. Obesity and the risk of heart failure. N Engl J Med 2002;347:305—13. [7] Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968—77. [8] Alpert MA, Terry BE, Mulekar M, Cohen MV, Massey CV, Fan TM, et al. Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss. Am J Cardiol 1997;80:736—40. [9] Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci 2001;321:225—36. [10] Huffman C, Wagman G, Fudim M, Zolty R, Vittorio T. Reversible cardiomyopathies — a review. Transplant Proc 2010;42:3673—8. [11] Alpert MA, Fraley MA, Birchem JA, Senkottaiyan N. Management of obesity cardiomyopathy. Expert Rev Cardiovasc Ther 2005;3:225—30. [12] Alpert MA, Lambert CR, Terry BE, Cohen MV, Mukerji V, Massey CV, et al. Influence of left ventricular mass on left ventricular diastolic filling in normotensive morbid obesity. Am Heart J 1995;130:1068—73. [13] Powell BD, Redfield MM, Bybee KA, Freeman WK, Rihal CS. Association of obesity with left ventricular remodeling and diastolic dysfunction in patients without coronary artery disease. Am J Cardiol 2006;98:116—20. [14] Lavie CJ, Messerli FH. Cardiovascular adaptation to obesity and hypertension. Chest 1986;90:275—9. [15] Alexander JK. Obesity and the heart. Heart Dis Stroke 1993;2:317—21. [16] Listenberger LL, Schaffer JE. Mechanisms of lipoapoptosis: implications for human heart disease. Trends Cardiovasc Med 2002;12:134—8. [17] Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A 2000;97:1784—9. [18] Banerjee S, Peterson LR. Myocardial metabolism and cardiac performance in obesity and insulin resistance. Curr Cardiol Rep 2007;9:143—9.
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[19] Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 2004;109:2191—6. [20] McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. Ann Intern Med 2006;144:517—24. [21] Shibata R, Ouchi N, Ito M, Kihara S, Shiojima P, Pimentel DR, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 2004;10:1384—9. [22] Harte A, McTernan P, Chetty R, Coppack S, Katz J, Smith S, et al. Insulin-mediated upregulation of the renin angiotensin system in human subcutaneous adipocytes is reduced by rosiglitazone. Circulation 2005;111:1954—61. [23] Hamdy O. Lifestyle modification and endothelial function in obese subjects. Expert Rev Cardiovasc Ther 2005;3(2):231—41. [24] Knowler KC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EH, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346(6):393—403. [25] Thörne A, Lönnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 2002;26(2): 193—9. [26] Miyatake N, Takahashi K, Wada J, Nishikawa H, Morishita A, Suzuki H, et al. Daily exercise lowers blood pressure and reduces visceral adipose tissue areas in overweight Japanese men. Diabetes Res Clin Pract 2003;62(3):149—57. [27] Alexander JK. Appendix. In: Alpert MA, Alexander JK, editors. The Heart and Lung in Obesity. NY, USA: Futura Publishing; 1998. p. 239—43. [28] Mehra MR, Kobashigawa J, Starling R, Russell S, Uber PA, Parameshwar J, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates — 2006. J Heart Lung Transplant 2006;25:1024—42. [29] Alsabrook GD, Goodman HR, Alexander JW. Gastric bypass for morbidly obese patients with established cardiac disease. Obes Surg 2006;16:1272—7. [30] Ashrafian H, le Roux CW, Darzi A, Athanasiou T. Effects of bariatric surgery on cardiovascular function. Circulation 2008;118:2091—102. [31] Reigle J. Heart failure, obesity and bariatric surgery. Prog Cardiovasc Nurs 2009;24:36—8. [32] Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc 2005;80:1157—62. [33] McCloskey CA, Ramani GV, Mathier MA, Schauer PR, Eid GM, Mattar SG, et al. Bariatric surgery improves cardiac function in morbidly obese patients with severe cardiomyopathy. Surg Obes Relat Dis 2007;3:503—7.
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