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Metabolic or Pseudometabolic Syndrome?Luis Cláudio Lemos Correia1, Adriana L. Latado2, José Augusto Barreto-Filho3 Escola Bahiana de Medicina1; Universidade Federal da Bahia2, Salvador/BA; Universidade Federal de Sergipe3, Aracaju, SE, Brazil A predictive model is created based on the following: (1) Metabolic syndrome has been proposed as a predictor of identification of variables associated with an outcome in cohort cardiovascular risk. However, such idea lacks strong scientific studies, which are submitted to (2) multivariate analysis that basis. This article reviews the evidence regarding that issue, defines which are the independent predictors of outcome challenging the existing paradigm of the prognostic value of and the relative value of each one. Drawing on such data, (3) those predictors are attributed points proportionally to their force of association with the outcome, generating a risk score. According to Hans Christian Andersen’s tale (1837), once That was how the classical Framingham Score was created3. upon a time there lived a vain Emperor who ordered from two tailors an extraordinary suit, of such unique quality that Differently, the metabolic syndrome has not been created nobody had ever seen a similar one. As the tailors could not based on the independent association between outcome and each of those components. In a simpler strategy, experts fulfill the Emperor’s wish, they conceived a wonderful suit, have clustered clinical and laboratory findings based on which would be invisible to anyone who was too stupid to the assumption of a single pathophysiological construct, appreciate its quality. The Emperor himself, while trying on his in which insulin resistance would provide the explicative new clothes, could not see them on the mirror, but pretended link for the different metabolic abnormalities. This has little to see them so as not to appear stupid. Similarly, everybody if any relationship with risk prediction. In addition, studies could see that the Emperor was naked, but nobody admitted have shown that the prognostic accuracy of the Framingham it, since nobody was willing to admit his own stupidity. Thus, Score is clearly superior to that of the metabolic syndrome for the Emperor spent a long time naked, exposed to ridicule. predicting cardiovascular events, and that the latter does not This tale explains why some medical myths last for so long, despite the lack of scientific basis. The metabolic syndrome, Stern et al4 have assessed the prognostic value of those as an entity of great clinical value, seems to be a myth to be two models regarding cardiovascular events in a cohort of challenged. In reality, that entity holds a huge dissociation 1,709 non-diabetic individuals4. In the univariate analysis, between its popularity and its real usefulness in medical the odds ratio of the Framingham Score was 9.7 (95% decision making. The metabolic syndrome can be defined confidence interval [CI] = 6.7 – 14), clearly superior to as the clustering of at least three of the following five criteria: that of the metabolic syndrome, 4.0 (95% CI = 2.8 – 5.6). increased abdominal circumference; high triglyceride levels; Even more important, when both predictive models were low HDL-cholesterol levels; high blood pressure; and glycemia tested using multivariate analysis, the Framingham Score ≥ 100 mg/dl1. That concept has gained importance with the remained with odds ratio of 9.1 (95% CI = 6.0 – 14), while seminal study by Reaven2, proposing a pathophysiological the metabolic syndrome lost statistical significance (odds model in which insulin resistance/hyperinsulinemia would be ratio = 1.1; 95% CI = 0.76 – 1.7). Similarly, the area under the link responsible for the clustering of the cardiovascular risk the receiver operating characteristic (ROC) curve of the factors commonly observed in clinical practice.
Framingham Score was 0.82, as compared with 0.81 after However, extrapolating that pathophysiological hypothesis incorporating the diagnosis of metabolic syndrome into the to the creation of a concept of metabolic syndrome used to Framingham model. Thus, there is no incremental prognostic predict cardiovascular events and the development of diabetes value in using the diagnosis of metabolic syndrome along has not been well founded, exemplifying how myths can be created. Therefore, this brief review aimed at assessing, based Wannamethee et al5 have reported the area under the on scientific evidence, whether metabolic syndrome really ROC curve of the Framingham Score and the number of criteria for the metabolic syndrome in a cohort of 5,128 men of the British Regional Heart Study5. The Framingham Score had an area under the ROC curve of 0.73 (95% CI = 0.71 – 0.75), greater than the accuracy of the metabolic syndrome (0.63; 95% CI = 0.61 – 0.65) in predicting coronary events Risk factors; diabetes mellitus; obesity; abdominal (p < 0.001). Likewise, in the cohort of 12,089 individuals of the Atherosclerosis Risk in Communities (ARIC) study, Mailing Address: Luis Cláudio Lemos Correia •
the area under the ROC curve of the Framingham Score Av. Princesa Leopoldina 19/402- Graça – 40150-080 – Salvador, BA – Brazil was similar, with or without incorporating the definition of, Manuscript received September 20, 2011; revised manuscript received metabolic syndrome, in women (0.729 vs. 0.731) and men September 21, 2011; accepted December 20, 2011.
Correia et al
Metabolic or Pseudometabolic Syndrome?
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The excessive attention given to metabolic syndrome has the anorexigenic drug Rimonabant (already removed from caused some confusion in medical reasoning. An example the market) had its marketing campaign based on the “cure” is the mistake of the Brazilian Guidelines on Dyslipidemia of metabolic syndrome. When someone is labeled as having in suggesting that the presence of metabolic syndrome metabolic syndrome, a procedure such as bariatric surgery might should reclassify patients at intermediate cardiovascular risk seem justifiable in someone without morbid obesity, even without according to the Framingham Score to high risk7. In that the necessary scientific validation. Tests to assess myocardial context, it has been recommended that the presence of ischemia might seem plausible when applied to a patient with metabolic syndrome corrects the Framingham classification. metabolic syndrome, even when asymptomatic. And so forth. However, it is questionable, and even surprising, that That is medicalization of society induced by labels for diseases.
a better predictor be corrected by a worse predictor, Thus, returning to the tale of the Emperor’s new clothes. One especially when the worse predictor does not add any value day, during a ceremonial parade in the streets of the village, when the Emperor passed wearing his “marvelous” clothes, one child Another argument used in favor of the metabolic syndrome shouted: the Emperor is naked! That child unveiled the tailors’ is the prediction of the development of diabetes. In trick, embarrassed the Emperor, and especially the people who fact, metabolic syndrome predicts diabetes better believed in the lie or were ashamed to disagree. Some people than the Framingham Score5. However, when the say it was the child’s innocence that allowed him/her to speak metabolic syndrome is compared with models created to frankly. In reality, legend has it that the child was mischievous. In predict diabetes, the latter show better predictive capacity that case, the difference between the child and the adult was the than metabolic syndrome4. Once again, that is expected, recognition of the naked truth. Briefly, the tale of the Metabolic because the clustering of risk factors that define the Syndrome teaches us that scientific knowledge is not always diagnosis of metabolic syndrome is not in accordance with based on assumptions. Only questioning and scientific debate the scientific assumptions that have founded the creation of risk prediction models. Thus, for diabetes prediction, the most adequate are multivariate models derived from cohort Potential Conflict of Interest
studies. It is worth noting that the simple fasting glycemia No potential conflict of interest relevant to this article was is a better predictor of diabetes than the definition of metabolic syndrome. For example, in the cohort of the PROSPER study, the hazard ratio of the metabolic syndrome for predicting diabetes was 4.4 as compared with 18.4 of Sources of Funding
There were no external funding sources for this study.
Thus, one should question why so much emphasis on the metabolic syndrome. The excessive attention given to Study Association
that syndrome originates from our culture of creating labels for diseases. Based on those labels, complementary tests, This study is not associated with any post-graduation medications and complex procedures are justified. For example, References1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et 5. Wannamethee SG, Shaper AG, Lennon L. Metabolic syndrome vs al. Harmonizing the Metabolic Syndrome: A Joint Interim Statement of the Framingham risk score for prediction of coronary heart disease, stroke, and International Diabetes Federation Task Force on Epidemiology and Prevention; type 2 Diabetes Mellitus. Arch Intern Med. 2005;165(22):2644-50.
National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International 6. McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East HE, Association for the Study of Obesity. Circulation. 2009;120(16):1640-5.
et al. The Metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care 2. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes .1988;37(12):1595-607.
7. Sposito AC, Caramelli B, Fonseca FA, Bertolami MC, Afiune NA, Souza AD, 3. D’Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. et al;/Brazilian Society of Cardiology. [IV Brazilian guideline for dyslipidemia General Cardiovascular risk profile for use in primary care: The Framingham and atherosclerosis prevention: Arq Bra.Cardiol. 2007;88( Suppl 1):2-19.
Heart Study. Circulation .2008;117(6):743-53.
8. Sattar N, McConnachie A, Shaper AG, Blauw GJ, Buckley BM, de Craen 4. Stern MP, Williams K, Gonzalez-Villalpando C, Hunt KJ, Haffner SM. Does AJ, et al. Can metabolic syndrome usefully predict cardiovascular disease the metabolic syndrome improve identification of individuals at risk of type 2 and diabetes? Outcome data from two prospective studies. Lancet. diabetes and/or cardiovascular disease? Diabetes Care .2004;27(11):2676-81.


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