Current Understanding of Multiple Risk Factors as the Metabolic Syndrome: Distillation or Deconstruction

ABSTRACT

The “metabolic syndrome” is a new term that defines the clustering of vascular risk factors, such as hyperlipidemia, obesity, elevated blood pressure, and elevated blood glucose. Controversy exists regarding the use of the term, which raises the question of whether the unique grouping of vascular risk factors adds more clinical risk then the additive effect of multiple risk factors viewed as separate but important entities. Whatever the answer, the metabolic syndrome constitutes a major public health problem with over 47 million persons in the United States meeting criteria for the metabolic syndrome. Although studies have demonstrated that the metabolic syndrome is a risk factor for overall mortality as well as cardiovascular events, the relationship between the metabolic syndrome and ischemic stroke has not been well characterized. Two large cross-sectional studies report an association between metabolic syndrome and increased risk of a history of stroke. One large multiethnic prospective study found the metabolic syndrome to be significantly associated with an increased risk of ischemic stroke after adjustment for sociodemographics and other cardiovascular risk factors. This study estimated that the metabolic syndrome may account for 19% of ischemic strokes including 30% of stroke in women and over 40% of stroke in Hispanics. Despite debate about the utility of its definition, there is evidence to suggest that the metabolic syndrome is an important risk factor for ischemic stroke, with differential effects by gender and race-ethnicity. Further, the metabolic syndrome has important clinical and public health implications by helping to easily identify individuals at greatest risk of vascular events.

Metabolic syndrome - stroke risk factors - insulin resistance

REFERENCES

• 1 Sacco R. Stroke risk factors: an overview. In: Norris JW Stroke Prevention. New York; Oxford University Press 2001: 17-42
• 2 Ford E S, Giles W H, Dietz W H. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey.  JAMA. 2002;  287 356-359
• 3 Haffner S, Taegtmeyer M. Epidemic obesity and the metabolic syndrome.  Circulation. 2003;  108 1541-1545
• 4 Ferrannini E, Balkau B. Insulin: in search of a syndrome.  Diabet Med. 2002;  19 724-729
• 5 Lakka H, Laaksonen D, Lakka T et al.. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.  JAMA. 2002;  288 2709-2716
• 6 Reaven G. Banting Lecture 1988: role of insulin resistance in human disease.  Diabetes. 1988;  37 1595-1607
• 7 Haffner S, Taegtmeyer H. Epidemic obesity and the metabolic syndrome.  Circulation. 2003;  108 1541-1545
• 8 Hanley A, Karter A, Festa A et al.. Insulin resistance and atherosclerosis study.  Diabetes. 2002;  51 2642-2647
• 9 World Health Organization .Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva, Switzerland; Department of Noncommunicable Disease Surveillance, World Health Organization 1999
• 10 Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults . Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III).  JAMA. 2001;  285 2486-2497
• 11 Ford E, Giles W, Mokdad A. Increasing prevalence of the metabolic syndrome among US adults.  Diabetes Care. 2004;  27 2444-2449
• 12 Cook S, Weitzman M, Auinger P, Nguyen M, Dietz W H. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994.  Arch Pediatr Adolesc Med. 2003;  157 821-827
• 13 Duncan G, Li S, Zhou X. Prevalence and trends of a metabolic syndrome phenotype among US adolescents, 1999-2000.  Diabetes Care. 2004;  27 2438-2443
• 14 Scott C L. Diagnosis, prevention, and intervention for the metabolic syndrome.  Am J Cardiol. 2003;  92 35i-42i
• 15 Boden-Albala B, Lee H, Sacco R L. Stroke risk and the metabolic syndrome: findings from the Northern Manhattan Stroke Study.  Neurology. 2003;  60 A255
• 16 Meigs J B, Wilson P W, Nathan D M, D'Agostino Sr R B, Williams K, Haffner S M. Prevalence and characteristics of the metabolic syndrome in the San Antonio Heart and Framingham Offspring Studies.  Diabetes. 2003;  52 2160-2167
• 17 Lin H F, Boden-Albala B, Juo S H, Park N, Rundek T, Sacco R L. Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study.  Diabetologia. 2005;  48 2006-2012
• 18 Sacco R L, Boden-Albala B, Abel G et al.. Race-ethnic disparities in the impact of stroke risk factors: the Northern Manhattan Stroke Study.  Stroke. 2001;  32 1725-1731
• 19 Fernandez J, Allison D. Understanding racial differences in obesity and metabolic syndrome traits.  Nutr Rev. 2003;  61 316-320
• 20 Haffner S, Gonzalez Villalpando C, Hazuda H P, Valdez R, Mykkanen L, Stern M. Prevalence of hypertension in Mexico City and San Antonio, Texas.  Circulation. 1994;  90 1542-1549
• 21 Despres J P, Lamarche B, Mauriege P et al.. Hyperinsulinemia as an independent risk factor for ischemic heart disease.  N Engl J Med. 1996;  334 952-957
• 22 Denke M. Connections between obesity and dyslipidemia.  Curr Opin Lipidol. 2001;  12 625-628
• 23 Hsia J, Bittner V, Tripputi M, Howard B V. Metabolic syndrome and coronary angiographic disease progression: the Women's Angiographic Vitamin & Estrogen Trial.  Am Heart J. 2003;  146 439-445
• 24 Lapidus L, Bengstsson C, Larsson B et al.. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12-year follow-up of participants in the population study of women in Gothenburg, Sweden.  Br Med J (Clin Res Ed). 1984;  289 1257-1261
• 25 Ducimetiere P, Eschwege E, Papoz L, Richard J L, Claude J R, Rosselin G. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population.  Diabetologia. 1980;  19 205-210
• 26 Folsom A R, Szklo M, Stevens J, Liao F, Smith R, Eckfeldt J H. A prospective study of coronary heart disease in relation to fasting insulin, glucose, and diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.  Diabetes Care. 1997;  20 935-942
• 27 Klein B, Klein R, Lee K. Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in Beaver Dam.  Diabetes Care. 2002;  25 1790-1794
• 28 Ninomiya J, L'Italian G, Criqui M, Whyte J. Association of the metabolic syndrome with a history and stroke in the Third National Health and Nutrition Examination Survey.  Circulation. 2004;  109 42-46
• 29 Pyorala M, Miettinen H, Laakso M, Pyorala K. Hyperinsulinemia and the risk of stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki policemen study.  Stroke. 1998;  29 1860-1866
• 30 Hu G, Qiao Q, Tuomilehto J et al.. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in non-diabetic European men and women.  Arch Intern Med. 2004;  164 1066-1076
• 31 Ridker P M, Bassuk S S, Toth P P. C-reactive protein and risk of cardiovascular disease: evidence and clinical application.  Curr Atheroscler Rep. 2003;  5 341-349
• 32 Ridker P, Buring J, Cook N, 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
• 33 Hu G, Qiao Q, Tuomilehto J. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in non-diabetic European men and women.  Arch Intern Med. 2004;  164 1066-1076
• 34 Wilson P, Kannel W, Silbershatz H, D'Agostino R. Clustering of metabolic factors and coronary heart disease.  Arch Intern Med. 1999;  159 1104-1109
• 35 Sprecher D L, Pearce G L. How deadly is the “deadly quartet”? A post CABG evaluation.  J Am Coll Cardiol. 2000;  36 1159-1165
• 36 Isomaa B, Almgren P, Tuomi T et al.. Cardiovascular morbidity and mortality associated with the metabolic syndrome.  Diabetes Care. 2001;  24 683-689
• 37 Pyorala K, Ballantyne C, Gumbiner B et al.. Reduction of cardiovascular events by simvastatin in nondiabetic coronary heart disease patients with and without the metabolic syndrome.  Diabetes Care. 2004;  27 1735-1740
• 38 Li W, Girard P, Boissel J, Gueyffier F. The calculation of a confidence interval on the absolute estimated benefit for an individual patient.  Comput Biomed Res. 1998;  31 244-256
• 39 Poulsen P. Genetic versus environmental aetiology of the metabolic syndrome among male and female twins.  Diabetologia. 2001;  44 537-543
• 40 Freeman M. Heritability of features of the insulin resistance syndrome in a community-based study of healthy families.  Diabet Med. 2002;  19 994-999
• 41 Olswold C, de Andrade M. Localization of genes involved in the metabolic syndrome using multivariate linkage analysis.  BMC Genet. 2003;  4(suppl 1) S57
• 42 Edwards K L, Newman B, Mayer E, Selby J V, Krauss R M, Austin M A. Heritability of factors of the insulin resistance syndrome in women twins.  Genet Epidemiol. 1997;  14 241-253
• 43 Brook R D, Glazewski L, Rajagopalan S, Bard R L. Hypertension and triglyceride catabolism: implications for the hemodynamic model of the metabolic syndrome.  J Am Coll Nutr. 2003;  22 290-295
• 44 Folsom A R, Rasmussen M L, Chambless L E et al.. Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study Investigators.  Diabetes Care. 1999;  22 1077-1083
• 45 Howard G, O'Leary D H, Zaccaro D et al.. Insulin sensitivity and atherosclerosis: the Insulin Resistance Atherosclerosis Study (IRAS) Investigators.  Circulation. 1996;  93 1809-1817
• 46 Kernan W N, Inzucchi S E, Viscoli C M, Brass L M, Bravata D M, Horwitz R I. Insulin resistance and risk for stroke.  Neurology. 2002;  59 809-815
• 47 Sakkinen P A, Wahl P, Cushman M, Lewis M R, Tracy R P. Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome.  Am J Epidemiol. 2000;  152 897-907
• 48 Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin's vascular effects in humans.  J Clin Invest. 1994;  94 2511-2515
• 49 Weiss R, Dziura J, Burgert T et al.. Obesity and the metabolic syndrome in children and adolescents.  N Engl J Med. 2004;  350 2362-2374
• 50 Blake G, Ridker P. Inflammatory bio-markers and cardiovascular risk prediction.  J Intern Med. 2002;  252 283-294
• 51 Grundy S, Hansen B, Smith S. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management.  Circulation. 2004;  109 551-556
• 52 Wong N D, Pio J R, Franklin S S, L'Italien G J, Kamath T V, Williams G R. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome.  Am J Cardiol. 2003;  91 1421-1426
• 53 Malik S, Wong N D, Franklin S et al.. Impact of metabolic syndrome on mortality from coronary artery disease, cardiovascular disease, and all causes in United States.  Circulation. 2004;  110 1245-1250
• 54 Ferrannini E, Balkau B. Insulin: in search of a syndrome.  Diabet Med. 2002;  19 724-729
• 55 Meigs J B, Mittleman M A, Nathan D M et al.. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study.  JAMA. 2000;  283 221-228
• 56 Meigs J B. The metabolic syndrome.  BMJ. 2003;  327 61-62
• 57 Najarian R M, Sullivan L M, Kannel W B, Wilson P WF, D'agostino R B, Wolf P A. Metabolic syndrome compared with type 2 diabetes mellitus as a risk factor for stroke.  Arch Intern Med. 2006;  166 106-111
• 58 Pyorala M, Miettinen H, Laakso M, Pyorala K. Hyperinsulinemia and the risk of stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study.  Stroke. 1998;  29 1860-1866