Cardiovascular Complications of Obesity

  • M. Dominique Ashen
  • Roger S. Blumenthal
Part of the Nutrition and Health book series (NH)


Obesity is a costly public health epidemic which contributes to increased morbidity and mortality from cardiovascular disease (CVD) and diabetes mellitus (DM). Insulin resistance (IR), the crucial underlying link between obesity and CVD, is associated with adipose tissue dysfunction. IR drives unopposed upregulation of proinflammatory and prothrombic factors resulting in systemic inflammation, oxidative stress, and a prothrombic environment. Among the resultant effects are hypertension, atherogenic dyslipidemia, and impaired glycemic control, which are all risk factors for CVD. Inflammation and oxidative stress also underlie vascular endothelial dysfunction and a favorable milieu for the promotion of atherosclerosis. Through understanding the mechanisms by which IR links obesity to CVD, health professionals can educate their patients about ways to maintain weight loss and prevent weight gain and, thus, slow the obesity epidemic and reduce CVD morbidity and mortality.


Obesity Cardiovascular disease Insulin resistance 


  1. 1.
    Prevalence of obesity in the United States, 2009-2010. NCHS Data Brief No. 82; Jan 2012.
  2. 2.
  3. 3.
    Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer- and service-specific estimates. Health Aff (Millwood). 2009;28:w822–31.CrossRefGoogle Scholar
  4. 4.
    Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK. Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring). 2008;16:2323–30.CrossRefGoogle Scholar
  5. 5.
    Obesity in America. Harv Mens Health Watch . 2012;16(7): 5–7. (
  6. 6.
    Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162:1867–72.CrossRefPubMedGoogle Scholar
  7. 7.
    Zalesin KC, Franklin BA, Miller WM, Peterson ED, McCullough PA. Impact of obesity on cardiovascular disease. Endocrinol Metab Clin North Am. 2008;37:663–84.CrossRefPubMedGoogle Scholar
  8. 8.
    Strazzullo P, D’Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L. Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants. Stroke. 2010;41:e418–26.CrossRefPubMedGoogle Scholar
  9. 9.
    Suk SH, Sacco RL, Boden-Albala B, Cheun JF, Pittman JG, Elkind MS, Paik MC. Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study. Stroke. 2003;34:1586–92.CrossRefPubMedGoogle Scholar
  10. 10.
    Fox CS, Pencina MJ, Meigs JB, Vasan RS, Levitzky YS, D’Agostino Sr RB. Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s: the Framingham Heart Study. Circulation. 2006;113:2914–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med. 2001;345:790–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler III ER, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129(3):399–410.CrossRefPubMedGoogle Scholar
  13. 13.
    Agatston A. Why America is fatter and sicker than ever. Circulation. 2012;126:e3–35.CrossRefPubMedGoogle Scholar
  14. 14.
    Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study); case-control study. Lancet. 2004;364:937–52.CrossRefPubMedGoogle Scholar
  15. 15.
    Ninomiya JK, L’Italien G, Criqui MH, Whyte JL, Gamst A, Chen RS. Association of the metabolic syndrome with history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation. 2004;109:42–6.CrossRefPubMedGoogle Scholar
  16. 16.
    The Emerging Risk Factors Collaboration. Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease; collaborative analysis of 59 prospective studies. Lancet. 2011;377:1085–95.CrossRefPubMedCentralGoogle Scholar
  17. 17.
    Gruson E, Montaye M, Kee F, Wagner A, Bingham A, Ruidavets JB, Haas B, Evans A, Ferrieres J, Ducimetiere PP, Amouyel P, Dallongeville J. Anthropometric assessment of abdominal obesity and coronary heart disease risk in men: the PRIME study. Heart. 2010;96:136–40.CrossRefPubMedGoogle Scholar
  18. 18.
    Canoy D, Boekholdt SM, Wareham N, Luben R, Welch A, Bingham S, Buchan I, Day N, Khaw KT. Body fat distribution and risk of coronary heart disease in men and women in the European Prospective Investigation into Cancer and Nutrition in Norfolk cohort: a population-based prospective study. Circulation. 2007;116:2933–43.CrossRefPubMedGoogle Scholar
  19. 19.
    Reaven G. Insulin resistance and coronary heart disease in nondiabetic individuals. Arterioscler Thromb Vasc Biol. 2012;32:1754–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365:1415–28.CrossRefPubMedGoogle Scholar
  21. 21.
    Nguyen T, Lau DCW. The obesity epidemic and its impact on hypertension. Can J Cardiol. 2012;28:326–33.CrossRefPubMedGoogle Scholar
  22. 22.
    Lau DCW. Molecular biology of obesity. In: Rees MCP, Karoshi M, Keith L, editors. Obesity and pregnancy. London: Royal Society of Medicine Press Ltd.; 2008. p. 54–75.Google Scholar
  23. 23.
    Beltowski J, Wojcicka G, Marciniak A, Jamroz A. Oxidative stress, nitric oxide production and renal sodium handling in leptin-induced hypertension. Life Sci. 2004;74:2987–3000.CrossRefPubMedGoogle Scholar
  24. 24.
    Shankar A, Xiao J. Positive relationship between plasma leptin level and hypertension. Hypertension. 2010;56:623–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Lau DC, Dhillon B, Yan H, Szmitko PE, Verma S. Adipokines: molecular links between obesity and atherosclerosis. Am J Physiol Heart Circ Physiol. 2005;288:H2031–41.CrossRefPubMedGoogle Scholar
  26. 26.
    Dorresteijn JA, Visseren FL, Spiering W. Mechanisms linking obesity to hypertension. Obes Rev. 2012;13:17–26.CrossRefPubMedGoogle Scholar
  27. 27.
    Wang ZV, Scherer PE. Adiponectin, cardiovascular function and hypertension. Hypertension. 2008;51:8–14.CrossRefPubMedGoogle Scholar
  28. 28.
    Ouchi N, Ohashi M, Kihara S, Funahashi T, Nakamura T, Nagaretani H, et al. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension. 2003;42:231–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Tan KC, Xu A, Chow WS, Lam MC, Ai VH, Tam SC, et al. Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab. 2004;89:765–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Tonstad S, Despres JP. Treatment of lipid disorders in obesity. Expert Rev Cardiovasc Ther. 2011;9:1069–80.CrossRefPubMedGoogle Scholar
  31. 31.
    Bamba V, Rader DJ. Obesity and atherogenic dyslipidemia. Gastroenterology. 2007;132:2181–90.CrossRefPubMedGoogle Scholar
  32. 32.
    Adiels M, Olofsson SO, Taskinen MR, Boren J. Overproduction of very low density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28:1225–36.CrossRefPubMedGoogle Scholar
  33. 33.
    Aguilera CM, Gil-Campos M, Canete R, Gil A. Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome. Clin Sci. 2008;114:183–93.CrossRefPubMedGoogle Scholar
  34. 34.
    Garber AJ. Obesity and type 2 diabetes: which patients are at risk? Diabetes Obes Metab. 2012;14:399–408.CrossRefPubMedGoogle Scholar
  35. 35.
    Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: proxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab. 2004;89:463–78.CrossRefPubMedGoogle Scholar
  36. 36.
    Barbarroja N, Lopez-Pedrera R, Mayas MD, et al. The obese healthy paradox: is inflammation the answer? Biochem J. 2010;430:141–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Antuna-Puente B, Feve B, Fellahi S, Bastard JP. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab. 2008;34:2–11.CrossRefPubMedGoogle Scholar
  38. 38.
    Gauthier MS, Ruderman NB. Adipose tissue inflammation and insulin resistance; all obese humans are not created equal. Biochem J. 2010;430:e1–4.CrossRefPubMedGoogle Scholar
  39. 39.
    Lorenzo C, Williams K, Hunt KJ, Haffner SM. The National Cholesterol Education Program—Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes. Diabetes Care. 2007;30:8–13.CrossRefPubMedGoogle Scholar
  40. 40.
    Hajer GR, van Haeften TW, Visseren FL. Adipose tissue dysfunction in obesity, diabetes and vascular disease. Eur Heart J. 2008;29:2959–71.CrossRefPubMedGoogle Scholar
  41. 41.
    Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–808.CrossRefPubMedCentralPubMedGoogle Scholar
  42. 42.
    Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–61.CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010–3.CrossRefPubMedGoogle Scholar
  44. 44.
    Roos CJ, Quax PHA, Jukema JW. Cardiovascular metabolic syndrome: mediators involved in the pathophysiology from obesity to coronary heart disease. Biomark Med. 2012;6:35–52.CrossRefPubMedGoogle Scholar
  45. 45.
    Hansson GK. Inflammation, atherosclerosis and coronary artery disease. N Engl J Med. 2005;352:1685–95.CrossRefPubMedGoogle Scholar
  46. 46.
    Stephens JW, Khanolkar MP, Sc B. The biological relevance and measurement of oxidative stress in diabetes and cardiovascular disease. Atherosclerosis. 2009;202:321–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Anfossi G, Russo I, Doronzo G, Pomero A, Trovati M. Adipocytokines in atherothrombosis: focus on platelets and vascular smooth muscle cells. Mediators Inflamm. 2010;2010:174341.CrossRefPubMedCentralPubMedGoogle Scholar
  48. 48.
    Chapman MJ, Sposito AC. Hypertension and dyslipidemia in obesity and insulin resistance: pathophysiology, impact on atherosclerotic disease and pharmacotherapy. Pharmacol Ther. 2008;117:354–73.CrossRefPubMedGoogle Scholar
  49. 49.
    Campia U, Tesauro M, Cardillo C. Human obesity and endothelium dependent responsiveness. Br J Phamacol. 2012;165:561–73.CrossRefGoogle Scholar
  50. 50.
    Rajwani A, Cubbon RM, Wheatcroft SB. Cell-specific insulin resistance: implications for atherosclerosis. Diabetes Metab Res Rev. 2012;28:627–34.CrossRefPubMedGoogle Scholar
  51. 51.
    Eckel RH, Jakicic JM, Ard JD, Miller NH, Hubbard VS, Nonas CA, de Jesus JM, Sacks FM, Lee IM, Smith SC Jr, Lichtenstein AH, Svetkey LP, Loria CM, Wadden TW, Millen BE, Yanovski SZ. AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013. [Epub ahead of print]Google Scholar
  52. 52.
    Jensen MD, Ryan DH, Apovian CM, Loria CM, Ard JD, Millen BE, Comuzzie AG, Nonas CA, Donato KA, Pi-Sunyer FX, Hu FB, Stevens J, Hubbard VS, Stevens VJ, Jakicic JM, Wadden TA, Kushner RF, Wolfe BM, Yanovski SZ. AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2013. [Epub ahead of print]Google Scholar
  53. 53.
    Ferland A, Eckel RH. Does sustained weight loss reverse the metabolic syndrome? Curr Hypertens Rep. 2011;13:456–64.CrossRefPubMedGoogle Scholar
  54. 54.
    Anderssen S, Holme I, Urdal P, Hjermann I. Diet and exercise intervention have favorable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES). Blood Press. 1995;4:343–9.CrossRefPubMedGoogle Scholar
  55. 55.
    Van Gaal LF, Wauters MA, De Leeuw IH. The beneficial effects of modest weight loss on cardiovascular risk factors. Int J Obes Relat Metab Disord. 1997;21:S5–9.PubMedGoogle Scholar
  56. 56.
    Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:1343–50.CrossRefPubMedGoogle Scholar
  57. 57.
    Cornier MA, Marshall JA, Hill JO, Maahs DM, Eckel RH. Prevention of overweight/obesity as a strategy to optimize cardiovascular health. Circulation. 2011;124:840–50.CrossRefPubMedGoogle Scholar
  58. 58.
    Ravussin E, Bogardus C. A brief overview of human energy metabolism and its relationship to essential obesity. Am J Clin Nutr. 1992;55:242–5.Google Scholar
  59. 59.
    Leibl RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995;332:621–8.CrossRefGoogle Scholar
  60. 60.
    Weigle DS, Sande KJ, Iverius PH, Monsen ER, Brunzell JD. Weight loss leads to a marked decrease in non-resting energy expenditure in ambulatory human subjects. Metabolism. 1988;37:930–6.CrossRefPubMedGoogle Scholar
  61. 61.
    Rosenbaum M, Vandeborne K, Goldsmith R, Simoneau JA, Heymsfield S, Joanisse DR, Hirsch J, Murphy E, Matthews D, Segal KR, Leibel RL. Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects. Am J Physiol. 2003;285:R183–92.CrossRefGoogle Scholar
  62. 62.
    Bryson JM, King SE, Burns CM, Baur LA, Swaraj S, Caterson ID. Changes in glucose and lipid metabolism following weight loss produced by a very low calorie diet in obese subjects. Int J Obes Relat Metab Disord. 1996;20:338–45.PubMedGoogle Scholar
  63. 63.
    Wyatt HR, Grunwald GK, Seagle HM, Klem ML, McGuire MT, Wing RR, Hill JO. Resting energy expenditure in reduced-obese subjects in the National Weight Control Registry. Am J Clin Nutr. 1999;69:1189–93.PubMedGoogle Scholar
  64. 64.
    Filozof CM, Murua C, Sanchez MP, Brailovsky C, Perman M, Gonzalez CD, Ravussin E. Low plasma leptin concentration and low rates of fat oxidation in weight stable post obese subjects. Obes Res. 2000;8:205–10.CrossRefPubMedGoogle Scholar
  65. 65.
    Rosenbaum M, Nicolson M, Hirsch J, Murphy E, Chu F, Leibel RL. Effects of weight change on plasma leptin concentration and energy expenditure. J Clin Endocrinol Metab. 1997;82:3647–54.PubMedGoogle Scholar
  66. 66.
    Crujeiras AB, Goyenechea E, Abete I, Lage M, Carreira MC, Martinez JA, Casanueva FF. Weight gain after diet induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels. J Clin Endocrinol Metab. 2010;95:5037–44.CrossRefPubMedGoogle Scholar
  67. 67.
    Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ. Plasma ghrelin levels after diet induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346:1623–30.CrossRefPubMedGoogle Scholar
  68. 68.
    Essah PA, Levy JR, Sistrun SN, Kelly SM, Nestler JE. Effect of weight loss by a low fat diet and a low carbohydrate diet on peptide YY levels. Int J Obes (Lond). 2010;34:1239–42.CrossRefGoogle Scholar
  69. 69.
    Walberg JL. Aerobic exercise and resistance weight training during weight reduction. Implications for obese persons and athletes. Sports Med. 1989;7:343–56.CrossRefPubMedGoogle Scholar
  70. 70.
    Hill JO, Wyatt HR, Reed GW, Peters JC. Obesity and the environment: where do we go from here? Science. 2003;299:853–5.CrossRefPubMedGoogle Scholar
  71. 71.
  72. 72.
    Bray GA, Ryan DH. Medical therapy for the patient with obesity. Circulation. 2012;125:1695–703.CrossRefPubMedGoogle Scholar
  73. 73.
    Poirier P, Cornier MA, Mazzone T, Stiles S, Cummings S, Klein S, et al. Bariatric surgery and cardiovascular risk factors: a scientific statement from the American Heart Association. Circulation. 2011;123:1683–701.CrossRefPubMedGoogle Scholar
  74. 74.
    Alexandrides TK, Skroubis G, Kalfarentzos F. Resolution of diabetes mellitus and metabolic syndrome following Roux-en-Y gastric bypass and a variant of biliopancreatic diversion in patient with morbid obesity. Obes Surg. 2007;17:176–84.CrossRefPubMedGoogle Scholar
  75. 75.
    Sjostrom L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, et al. Lifestyle, diabetes and cardiovascular risk factors 10 yrs after bariatric surgery. N Engl J Med. 2004;351:2683–93.CrossRefPubMedGoogle Scholar
  76. 76.
    Kreuter MW, Chheda SG, Bull FC. How does physician advice influence patient behavior? Evidence for a priming effect. Arch Fam Med. 2000;9:426–33.CrossRefPubMedGoogle Scholar
  77. 77.
    Post RE, Mainous III AG, Gregorie SH, Knoll ME, Diaz VA, Saxena SK. The influence of physician acknowledgment of patient’ weight status on patient perceptions of overweight and obesity in the United States. Arch Intern Med. 2011;171:316–21.CrossRefPubMedGoogle Scholar
  78. 78.
    Malterud K, Ulriksen K. Obesity in general practice: a focus group study on patient experiences. Scand J Prim Health Care. 2010;28:205–10.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • M. Dominique Ashen
    • 1
  • Roger S. Blumenthal
    • 1
  1. 1.Division of Cardiology, Department of MedicineJohns Hopkins Ciccarone Center for the Prevention of Heart DiseaseBaltimoreUSA

Personalised recommendations