Response to Letter by Sheikh
We thank Dr Kazim Sheikh for his remarks on our article published in Stroke.1 Dr Sheikh raises an important question as to why it is necessary to combine several cardiovascular risk factors into a syndrome called the metabolic syndrome (MetS) and determine its association with stroke. The concept of the MetS is based on the fact that certain cardiovascular risk factors cluster in individuals.2,3 The presence of this clustering approximately doubles the risk of atherosclerotic vascular disease over 5 to 10 years.2 The 6 definitions of the Mets have been designed by expert panels to provide clinicians with a tool to identify individuals with an increased risk for diabetes and cardiovascular disease.4 Most previous studies on the MetS, however, have used modified definitions other than proposed, and diabetic subjects have not been definitively excluded. Additional prospective data with hard cardiovascular end points and a comprehensive set of morphometric and metabolic markers was warranted to sort the key predictors of risk.5 Conseqeuntly, we investigated whether the MetS and its single components, defined by the 6 originally proposed criteria, predicted stroke in an elderly cohort of 991 nondiabetic Finnish subjects during a 14-year follow-up.1 The MetS defined by the 6 current criteria except for the ACE definition predicted stroke with hazard ratios (HRs) of 1.49 to 1.80 in nondiabetic subjects without coronary heart disease at baseline, verifying that the Mets criteria, indeed, are valuable in estimating the risk for stroke. We could also identify 3 single components of the MetS predicting stroke, impaired glucose tolerance by the World Health Organization (WHO) and ACE criteria (HR: 1.66); insulin resistance (HR: 1.60) by the European Group for the Study of Insulin Resistance (EGIR) criteria; and central obesity (HR: 1.52) by the National Cholesterol Education Program (NCEP) criteria. Impaired glucose tolerance alone was as strong a predictor of stroke as is the MetS defined by the WHO, NCEP and updated NCEP criteria. On the other hand, statistical analyses suggested that the Mets defined by 5 criteria was a stronger predictor of stroke events than its individual components, but this finding warrants further confirmation.
We agree with Dr Sheikh that the value of the MetS above and beyond its individual components to predict cardiovascular disease is uncertain. According to the encyclopedia, the term syndrome, deriving from the Greek and meaning literally “run together,” refers to the association of several clinically recognizable features, signs or characteristics that often occur together, so that the presence of one feature alerts the physician to the presence of others. Regarding the metabolic syndrome, several cardiovascular risk factors included in the syndrome are interrelated, and presence of obesity, particularly central obesity, should alert the physician to seek more insidious features of the syndrome, such as dyslipidemia, glucose tolerance disorders and insulin resistance. In contrast to the argument by Dr Sheikh, the term “syndrome” is most often used when the pathophysiology of the syndrome has not yet been discovered, although a familiar syndrome name often continues to be used even after the underlying cause has been found. Insulin resistance and abdominal obesity are likely to be the core abnormalities in the pathophysiology of the MetS.6,2
We agree with Dr Sheikh that in patient care, each individual cardiovascular risk factor should be treated. To assess and target global cardiometabolic risk, classic risk factors as well as the components of the MetS should be evaluated.4,5 We also agree with Dr Sheikh that as the components of the MetS are continuous variables, neither the current clinical criteria nor any new criteria for the MetS can exclusively define the syndrome, but rather provide a tool to help find the subjects with a high risk for diabetes and cardiovascular disease.4
Wang J, Ruotsalainen S, Moilanen L, Lepistö P, Laakso M, Kuusisto J. The metabolic syndrome predicts incident stroke: a 14-year follow-up study in elderly people in Finland. Stroke. 2008; 39: 1078–1083.
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F. 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.