Current Cardiology Reports

, Volume 9, Issue 6, pp 479–485 | Cite as

Cardiovascular risk in the metabolic syndrome: Fact or fiction?

Lipid Abnormalities and Cardiovascular Prevention


In population-based studies, a cluster of cardiovascular risk factors comprising the metabolic syndrome (MetS) has been documented as predictive of cardiovascular disease events and type 2 diabetes. Currently, there are several proposed definitions of the MetS, although data support some advantages of using the 2005 National Cholesterol Education Program Adult Treatment Panel III definition, which is considered superior to most others, including the one from the 2005 International Diabetes Federation study. One controversial issue is that some of the conventional cardiovascular risk factors included in the MetS cluster appear to be equally predictive of cardiovascular outcomes as the syndrome itself (eg, the influence of smoking habits). Further observational and intervention studies are needed to explore this issue and target the core problem of the syndrome, which is proposed to be insulin resistance. Useful therapies for the metabolic syndrome include lifestyle modification and drugs that lower conventional cardiovascular risk factors, such as metformin, the “glitazones”, and evidence-based drugs.


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References and Recommended Reading

  1. 1.
    De Backer G, Ambrosioni E, Borch-Johnsen K, et al.; Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice:European guidelines on cardiovascular disease prevention in clinical practice.Eur Heart J 2003,24:1601–1610.PubMedCrossRefGoogle Scholar
  2. 2.
    Yusuf S., Hawken S, Ounpuu S, et al.; INTERHEART Study Investigators:Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.Lancet 2004,364:937–952.PubMedCrossRefGoogle Scholar
  3. 3.
    Of importance Zethelius B, Lithell H, Hales CN, Berne C:Insulin sensitivity, proinsulin and insulin as predictors of coronary heart disease: a population-based 10-year, follow-up study in 70-year old men using the euglycaemic insulin clamp.Diabetologia 2005,48:862–867. One of very few studies with insulin sensitivity measured by clamp at baseline for long-term prediction of CHD events.PubMedCrossRefGoogle Scholar
  4. 4.
    De Fronzo RA, Ferrannini E.:Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease.Diabetes Care 1991,14:173–194.CrossRefGoogle Scholar
  5. 5.
    Reaven GM: Insulin resistance, cardiovascular disease, and the metabolic syndrome: how well do the emperor’s clothes fit?Diabetes Care 2004,27:1011–1012.PubMedCrossRefGoogle Scholar
  6. 6.
    Of major importance Kahn R, Buse J, Ferrannini E, Stern M; American Diabetes Association; European Association for the Study of Diabetes:The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes.Diabetes Care 2005,28:2289–2304. This critical paper sparked the debate on the usefulness of the MetS and resulted in heated arguments from both sides, also in defense of what is currently more often named Card Mets. Some observational studies have found the new IDF definition of MetS less useful for prediction of CVD than older definitions, for example the NCEP-ATP III definition.PubMedCrossRefGoogle Scholar
  7. 7.
    Gale EA:The myth of the metabolic syndrome.Diabetologia 2005,48:1679–1683.PubMedCrossRefGoogle Scholar
  8. 8.
    Kylin E:Studien über das hypertonie-hyperglykämie-hyperurikämisyndrom.Zeitschrift Innere Medizin 1923,7:105–112.Google Scholar
  9. 9.
    Reaven GM:Role of insulin resistance in human disease.Diabetes 1988,37:1595–1607.PubMedCrossRefGoogle Scholar
  10. 10.
    Barker DJ, ed.:Fetal and Infant Origins of Adult Disease. edn 1. London: BMJ; 1992.Google Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    Of importance Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group:The metabolic syndrome: a new worldwide definition.Lancet 2005,366:1059–1062. this paper proposed a new definition of MetS focused on increased waist circumference as the main criterion.PubMedCrossRefGoogle Scholar
  13. 13.
    Grundy SM, Cleeman JI, Daniels SR, et al.; American Heart Association; National Heart, Lung, and Blood Institute:Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.Circulation 2005,112:2735–2752.PubMedCrossRefGoogle Scholar
  14. 14.
    Isomaa B, Almgren P, Tuomi T, et al.:Cardiovascular morbidity and mortality associated with the metabolic syndrome.Diabetes Care 2001,24:683–689.PubMedCrossRefGoogle Scholar
  15. 15.
    Lakka HM, Laaksonen DE, Lakka TA, et al.:The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.JAMA 2002,288:2709–2716.PubMedCrossRefGoogle Scholar
  16. 16.
    Hu G, Qiao Q, Tuomilehto J, et al.; DECODE Group:Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women.Arch Intern Med 2004,164:1066–1076.PubMedCrossRefGoogle Scholar
  17. 17.
    McNeill AM, Rosamond WD, Girman CJ, et al.:The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study.Diabetes Care 2005,28:385–390.PubMedCrossRefGoogle Scholar
  18. 18.
    Of major importance Ford ES:Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence.Diabetes Care 2005,28:1769–1778. This is a timely meta-analysis based on data from several papers on risk of MetS for prediction of CVD events.PubMedCrossRefGoogle Scholar
  19. 19.
    Ford ES:Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the US.Diabetes Care 2005,28:2745–2749.PubMedCrossRefGoogle Scholar
  20. 20.
    Athyros VG, Ganotakis ES, Elisaf M, Mikhailidis DP:The prevalence of the metabolic syndrome using the National Cholesterol Educational Program and International Diabetes Federation definitions.Curr Med Res Opin 2005,21:1157–1159.PubMedCrossRefGoogle Scholar
  21. 21.
    Lawlor DA, Smith GD, Ebrahim S:Does, the new International Diabetes Federation definition of the metabolic syndrome predict CHD any more strongly than older definitions? Findings from the British Women’s Heart and Health Study.Diabetologia 2006,49:41–48.PubMedCrossRefGoogle Scholar
  22. 22.
    Conroy RM, Pyörälä K, Fitzgerald AP, et al.:Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.Eur Heart J 2003,24:987–1003.PubMedCrossRefGoogle Scholar
  23. 23.
    Of importance Nilsson PM, Engström G, Hedblad B:The metabolic syndrome and incidence of cardiovascular disease in nondiabetic subjects.Diabet Med 2007,24:464–472. In a population-based study, three definitions of MetS were compared for long-term prediction of cardiovascular events; the NCEP-ATP III turned out to be the most useful.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    Tong PC, Kong AP, So WY et al.:The usefulness of the International Diabetes Federation and the National Cholesterol Education Program’s Adult Treatment Panel III definitions of the metabolic syndrome in predicting coronary heart disease in subjects with type 2 diabetes.Diabetes Care 2007,30:1206–1211.PubMedCrossRefGoogle Scholar
  26. 26.
    Of importance Wang J, Ruotsalainen S, Moilanen L, et al.:The metabolic syndrome predicts cardiovascular mortality: a 13-year follow-up study in elderly non-diabetic Finns.Eur Heart J 2007,28:857–864. An important study comparing different definitions of MetS for prediction of CVD mortality in elderly subjects.PubMedCrossRefGoogle Scholar
  27. 27.
    Jeppesen J, Hansen TW, Rasmussen S, et al.:Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease: a population-based study J Am Coll Cardiol 2007,49:2112–2119.PubMedCrossRefGoogle Scholar
  28. 28.
    Guize L, Thomas F, Pannier B, et al.:All-cause mortality associated with specific combinations of the metabolic syndrome according to recent definitions.Diabetes Care 2007 [Epub ahead of print].Google Scholar
  29. 29.
    Pouliot MC, Després JP, Lemieux S, et al.:Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women.Am J Cardiol 1994,73:460–468.PubMedCrossRefGoogle Scholar
  30. 30.
    Han TS, van Leer EM, Seidell JC, Lean ME:Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample.BMJ 1985,311:1401–1405.Google Scholar
  31. 31.
    Jonsson S, Hedblad B, Engström G, et al.:Influence of obesity on cardiovascular risk: twenty-three-year follow-up of 22,025 men from an urban Swedish population.Int J Obes Relat Metab Disord 2002,26:1046–1053.PubMedCrossRefGoogle Scholar
  32. 32.
    Stern M, Williams K, Gonzalez-Villalpando C, et al.:Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease? Diabetes Care 2004,27:2676–2681.PubMedCrossRefGoogle Scholar
  33. 33.
    Mannucci E, Monami M, Cresci B, et al.:National Cholesterol Education Program and International Diabetes Federation definitions of metabolic syndrome in the prediction of diabetes. Results from the Flrenze-Bagno A Ripoli study.Diabetes Obes Metab 2007, [Epub ahead of print].Google Scholar
  34. 34.
    Sipilä K, Koivistoinen T, Moilanen L, et al.:Metabolic syndrome and arterial stiffness: the Health 2000 survey.Metab Clin Exp 2007,56:320–326.PubMedGoogle Scholar
  35. 35.
    Of major importance Laurent S, Cockcroft J, Van Bortel L, et al.; European Network for Non-invasive Investigation of Large Arteries:Expert consensus document on arterial stiffness: methodological issues and clinical applications.Eur Heart J 2006,27:2588–2605. This is a very important consensus position paper on the importance of arterial stiffness, one important component of cardiovascular risk evaluation, and how to measure it. Many patients with the MetS have early vascular aging and increased arterial stiffening.PubMedCrossRefGoogle Scholar
  36. 36.
    Hansson GK:Inflammation, atherosclerosis, and coronary artery disease.N Engl J Med 2005,352:1685–1695.PubMedCrossRefGoogle Scholar
  37. 37.
    Bots ML, Grobbee DE:Intima media thickness as a surrogate marker for generalised atherosclerosis Cardiovasc Drugs Ther 2002,16:341–351.PubMedCrossRefGoogle Scholar
  38. 38.
    Of importance Najjar SS, Scuteri A, Lakatta EG:Arterial aging: is it an immutable cardiovascular risk factor? Hypertension 2005,46:454–462. The new concept of early arterial aging and its determinants was discussed in this early review summarizing the present knowledge in this area.PubMedCrossRefGoogle Scholar
  39. 39.
    Jarvisalo MJ, Juonala M, Raitakari OT:Assessment of inflammatory markers and endothelial function.Curr Opin Clin Nutr Metab Care 2006,9:547–552.PubMedCrossRefGoogle Scholar
  40. 40.
    Samani NJ, Boulthy R, Butler R, et al.:Telomere shortening in atherosclerosis.Lancet 2001,358:472–473.PubMedCrossRefGoogle Scholar
  41. 41.
    Valdes AM, Andrew T, Gardner JP, et al.:Obesity cigarette smoking, and telomere length in women.Lancet 2005,366:662–664.PubMedCrossRefGoogle Scholar
  42. 42.
    Epel ES, Blackburn EH, Lin J, et al.:Accelerated telomere shortening in response to life stress.Proc Natl Acad Sci USA 2004,101:17312–17315.PubMedCrossRefGoogle Scholar
  43. 43.
    Epel ES, Lin J, Wilhelm FH, et al.:Cell aging in relation to stress arousal and cardiovascular disease risk factors.Psychoneuroendocrinology 2006,31:277–287.PubMedCrossRefGoogle Scholar
  44. 44.
    Brouilette S, Singh RK, Thompson JR, et al.:White cell telomere length and risk of premature myocardial infarction.Arterioscler Thromb Vasc Biol 2003,23:842–846.PubMedCrossRefGoogle Scholar
  45. 45.
    Of major importance Fitzpatrick AL, Kronmal RA, Gardner JP, et al.:Leukocyte telomere length and cardiovascular disease in the Cardiovascular Health Study.Am J Epidemiol, 2007,165:14–21. This is an important cohort follow-up study showing the importance of telomere length in association with increased risk of CVD in a population. Telomere attrition could be a marker of early biological aging, and useful in relation to risk of CVD as well as other complications.PubMedCrossRefGoogle Scholar
  46. 46.
    Cawthon RM, Smith KR, O’Brien E, et al.:Association between telomere length in blood and mortality in people aged 60 years or older.Lancet 2003,361:393–395.PubMedCrossRefGoogle Scholar
  47. 47.
    Taddei S, Virdis A, Mattei, P, et al.:Hypertension causes premature aging of endothelial function in humans.Hypertension 1997,29:736–743.PubMedGoogle Scholar
  48. 48.
    Hedblad B, Nilsson P, Janzon L, Berglund G:Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects: results from a cross-sectional study in Malmö, Sweden.Diabet Med 2000,17:299–307.PubMedCrossRefGoogle Scholar
  49. 49.
    Of importance Nilsson PM, Engström G, Hedblad, B, et al.:Plasma adiponectin levels are inversely associated with carotid intima media thickness and markers of insulin resistance in middle-aged men.Arterioscler Thromb Vasc Biol 2006,26:2758–2762. Adiponectin has been suggested as a marker of insulin sensitivity and glucose metabolism related to CVD risk. In this study, the relationship between low adiponectin level and increased IMT in the common carotid artery was confounded by glucometabolic control; therefore adiponectin is probably not an independent risk factor for early atherosclerosis.PubMedCrossRefGoogle Scholar
  50. 50.
    Hedblad B, Zambanini A, Nilsson P, et al.:Rosiglitazone and carotid IMT progression rate in a mixed cohort of patients with type 2 diabetes and the insulin resistance syndrome: main results from the Rosiglitazone Atherosclerosis Study.J Intern Med 2007,261:293–305.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.department of Clinical Sciences MedicineUniversity HospitalMalmöSweden

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