The Metabolic Syndrome and Atherogenesis

  • Viviane Z. Rocha
  • Peter Libby


The metabolic syndrome refers to a constellation of abnormalities that are ­associated with increased cardiometabolic risk. Important components of this cluster, such as visceral obesity, insulin resistance, a dyslipidemic state, a thrombotic diathesis, and an inflammatory profile, synergistically contribute to a higher risk of type 2 diabetes mellitus and cardiovascular disease. There is no universal agreement on exactly how to define the metabolic syndrome, as multiple bodies have established different sets of criteria for this condition. Moreover, not all agree it is actually a “syndrome.” Despite these issues, many think that the concept of the metabolic syndrome reflects high-risk individuals they often encounter in practice and, therefore, offers clinical utility. This chapter illustrates the components of the metabolic syndrome, how they associate with each other, and mechanisms by which they aggravate atherothrombosis.


High Risk Diabetes Mellitus Cardiovascular Disease Insulin Resistance Metabolic Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Despres JP, Lemieux I: Abdominal obesity and metabolic syndrome. Nature 2006, 444:881–887.CrossRefPubMedGoogle Scholar
  2. 2.
    Alberti KG, Zimmet PZ: Definition, diagnosis and classification of ­diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998, 15:539–553.CrossRefPubMedGoogle Scholar
  3. 3.
    Balkau B, Charles MA: Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999, 16:442–443.CrossRefPubMedGoogle Scholar
  4. 4.
    Alberti KG, Zimmet P, Shaw J: The metabolic syndrome—a new worldwide definition. Lancet 2005, 366:1059–1062.CrossRefPubMedGoogle Scholar
  5. 5.
    Einhorn D, Reaven GM, Cobin RH, et al. : American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 2003, 9:237–252.PubMedGoogle Scholar
  6. 6.
    Grundy SM, Cleeman JI, Daniels SR, et al. : Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005, 112:2735–2752.CrossRefPubMedGoogle Scholar
  7. 7.
    National Institutes of Health: Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001, 285:2486–2497.CrossRefGoogle Scholar
  8. 8.
    Van Gaal LF, Mertens IL, De Block CE: Mechanisms linking obesity with cardiovascular disease. Nature 2006, 444:875–880.CrossRefPubMedGoogle Scholar
  9. 9.
    Flegal KM, Carroll MD, Ogden CL, Curtin LR: Prevalence and trends in obesity among US adults, 1999-2008. JAMA 2010, 303:235–241.CrossRefPubMedGoogle Scholar
  10. 10.
    Van Cleave J, Gortmaker SL, Perrin JM: Dynamics of obesity and chronic health conditions among children and youth. JAMA 2010, 303:623–630.CrossRefPubMedGoogle Scholar
  11. 11.
    Kopelman PG: Obesity as a medical problem. Nature 2000, 404:635–643.PubMedGoogle Scholar
  12. 12.
    Ogden CL, Carroll MD, Curtin LR, et al. : Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006, 295:1549–1555.CrossRefPubMedGoogle Scholar
  13. 13.
    Rennie KL, Jebb SA: Prevalence of obesity in Great Britain. Obes Rev 2005, 6:11–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Wang Y, Monteiro C, Popkin BM: Trends of obesity and underweight in older children and adolescents in the United States, Brazil, China, and Russia. Am J Clin Nutr 2002, 75:971–977.PubMedGoogle Scholar
  15. 15.
    Tan CE, Ma S, Wai D, et al. : Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians? Diabetes Care 2004, 27:1182–1186.CrossRefPubMedGoogle Scholar
  16. 16.
    Despres JP, Lemieux I, Prud’homme D: Treatment of obesity: need to focus on high risk abdominally obese patients. BMJ 2001, 322:716–720.CrossRefPubMedGoogle Scholar
  17. 17.
    Rexrode KM, Carey VJ, Hennekens CH, et al. : Abdominal adiposity and coronary heart disease in women. JAMA 1998, 280:1843–1848.CrossRefPubMedGoogle Scholar
  18. 18.
    Rexrode KM, Buring JE, Manson JE: Abdominal and total adiposity and risk of coronary heart disease in men. Int J Obes Relat Metab Disord 2001, 25:1047–1056.CrossRefPubMedGoogle Scholar
  19. 19.
    Libby P, Ridker PM: Inflammation and atherothrombosis from population biology and bench research to clinical practice. J Am Coll Cardiol 2006, 48(Suppl):A33–46.CrossRefGoogle Scholar
  20. 20.
    Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000, 342:836–843.CrossRefPubMedGoogle Scholar
  21. 21.
    Ridker PM, Cushman M, Stampfer MJ, et al. : Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997, 336:973–979.CrossRefPubMedGoogle Scholar
  22. 22.
    Visser M, Bouter LM, McQuillan GM, et al. : Elevated C-reactive ­protein levels in overweight and obese adults. JAMA 1999, 282:2131–2135.CrossRefPubMedGoogle Scholar
  23. 23.
    Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW: C-reactive ­protein in healthy subjects. Associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999, 19:972–978.PubMedGoogle Scholar
  24. 24.
    Lemieux I, Pascot A, Prud’homme D, et al. : Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol 2001, 21:961–967.PubMedGoogle Scholar
  25. 25.
    Ridker PM, Buring JE, Cook NR, Rifai N: C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation 2003, 107:391–397.CrossRefPubMedGoogle Scholar
  26. 26.
    Hotamisligil GS: Inflammation and metabolic disorders. Nature 2006, 444:860–867.CrossRefPubMedGoogle Scholar
  27. 27.
    Rocha VZ, Libby P: Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol 2009, 6:399–409.CrossRefPubMedGoogle Scholar
  28. 28.
    Rocha VZ, Libby P: The multiple facets of the fat tissue. Thyroid 2008, 18:175–183.CrossRefPubMedGoogle Scholar
  29. 29.
    Kanda H, Tateya S, Tamori Y, et al. : MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006, 116:1494–1505.CrossRefPubMedGoogle Scholar
  30. 30.
    Weisberg SP, Hunter D, Huber R, et al. : CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 2006, 116:115–124.CrossRefPubMedGoogle Scholar
  31. 31.
    Weisberg SP, McCann D, Desai M, et al. : Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003, 112:1796–1808.PubMedGoogle Scholar
  32. 32.
    Wu H, Ghosh S, Perrard XD, et al. : T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 2007, 115:1029–1038.CrossRefPubMedGoogle Scholar
  33. 33.
    Rocha VZ, Folco EJ, Sukhova G, et al. : Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ Res 2008, 103:467–476.CrossRefPubMedGoogle Scholar
  34. 34.
    Hotamisligil GS, Shargill NS, Spiegelman BM: Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993, 259:87–91.CrossRefPubMedGoogle Scholar
  35. 35.
    Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM: Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci U S A 1994, 91:4854–4858.CrossRefPubMedGoogle Scholar
  36. 36.
    Okamoto Y, Kihara S, Funahashi T, et al. : Adiponectin: a key adipocytokine in metabolic syndrome. Clin Sci (Lond) 2006, 110:267–278.CrossRefGoogle Scholar
  37. 37.
    Arita Y, Kihara S, Ouchi N, et al. : Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999, 257:79–83.CrossRefPubMedGoogle Scholar
  38. 38.
    Ouchi N, Kihara S, Arita Y, et al. : Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999, 100:2473–2476.PubMedGoogle Scholar
  39. 39.
    Schenk S, Saberi M, Olefsky JM: Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 2008, 118:2992–3002.CrossRefPubMedGoogle Scholar
  40. 40.
    Shi H, Kokoeva MV, Inouye K, et al. : TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 2006, 116:3015–3025.CrossRefPubMedGoogle Scholar
  41. 41.
    Kawakami A, Osaka M, Aikawa M, et al. : Toll-like receptor 2 mediates apolipoprotein CIII-induced monocyte activation. Circ Res 2008, 103:1402–1409.CrossRefPubMedGoogle Scholar
  42. 42.
    Kawakami A, Yoshida M: Apolipoprotein CIII links dyslipidemia with atherosclerosis. J Atheroscler Thromb 2009, 16:6–11.PubMedGoogle Scholar
  43. 43.
    Kinlay S, Libby P, Ganz P: Endothelial function and coronary artery disease. Curr Opin Lipidol 2001, 12:383–389.CrossRefPubMedGoogle Scholar
  44. 44.
    Creager MA, Luscher TF, Cosentino F, Beckman JA: Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy, part I. Circulation 2003, 108:1527–1532.CrossRefPubMedGoogle Scholar
  45. 45.
    Alessi MC, Juhan-Vague I: Metabolic syndrome, haemostasis and thrombosis. Thromb Haemost 2008, 99:995–1000.PubMedGoogle Scholar
  46. 46.
    Sakkinen PA, Wahl P, Cushman M, et al. : Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. Am J Epidemiol 2000, 152:897–907.CrossRefPubMedGoogle Scholar
  47. 47.
    Rau JC, Beaulieu LM, Huntington JA, Church FC: Serpins in thrombosis, hemostasis and fibrinolysis. J Thromb Haemost 2007, 5(Suppl 1): 102–115.CrossRefPubMedGoogle Scholar
  48. 48.
    Englyst NA, Taube JM, Aitman TJ, et al. : A novel role for CD36 in VLDL-enhanced platelet activation. Diabetes 2003, 52:1248–1255.CrossRefPubMedGoogle Scholar
  49. 49.
    Korporaal SJ, Akkerman JW: Platelet activation by low density lipoprotein and high density lipoprotein. Pathophysiol Haemost Thromb 2006, 35:270–280.CrossRefPubMedGoogle Scholar
  50. 50.
    Libby P, Plutzky J: Diabetic macrovascular disease: the glucose paradox? Circulation 2002, 106:2760–2763.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Viviane Z. Rocha
    • 1
  • Peter Libby
    • 2
  1. 1.Cardiovascular Division, Department of MedicineBrigham and Women’s HospitalBostonUSA
  2. 2.Cardiovascular Division, Harvard Medical SchoolBrigham and Women’s HospitalBostonUSA

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