It is well recognised that type 2 diabetes is associated with a high risk of macrovascular complications representing the major cause of death in this population. 1 However, recent evidence has shown that the elevated metabolic risk is not confined to the impaired glucose tolerance and type 2 diabetes categories, and that the Metabolic Syndrome increases the risk of cardiovascular disease, even in the absence of type 2 diabetes. Very recent prospective studies have demonstrated that patients suffering from the Metabolic Syndrome are about three times more likely to experience cardiovascular events than those free of the syndrome. ^2,3

Figure 1: Age-adjusted prevalence of the features of the Metabolic Syndrome according to sex.

The presence of the Metabolic Syndrome is associated with an increased risk of coronary heart disease, myocardial infarction, and stroke in both sexes. ³ This substantial increased risk of cardiovascular morbidity and mortality associated with the presence of the Metabolic Syndrome appeared as independent of other important and potentially confounding factors, such as smoking, plasma LDL-cholesterol levels, and alcohol consumption. ² Interestingly, the Metabolic Syndrome entails also a high cardiovascular risk in subjects with a personal history of cardiovascular disease and in type 2 diabetic patients. 3 Moreover, the deleterious impact of the Metabolic Syndrome on cardiovascular disease and coronary heart disease mortality has also been observed in normoglycaemic patients and in those with impaired fasting glycaemia or glucose intolerance, suggesting that a cluster of metabolic factors increases the cardiovascular risk across the whole spectrum of the glucose status. 2,3 In terms of pathophysiology, the association of metabolic abnormalities represents a highly atherogenic state promoting the formation and growth of atheroma plaques in arteries. It has been recognised that insulinresistance/hyperinsulinaemia and the underlying consequences related to defects in insulin metabolism are associated with the presence of cardiovascular risk factors such as hypertriglyceridaemia, low HDL-cholesterol, hypertension, abdominal obesity, impaired fibrinolytic system capacity even in the absence of diabetes.

These findings underscore the need to consider the cardiovascular risk of individuals beyond the presence of diabetes or intolerance to glucose with a specific attention to the presence of the features of the Metabolic Syndrome. In these epidemiological studies, the risk of cardiovascular events conferred by the presence of the Metabolic Syndrome was greater than the risk associated with any of the individual components, emphasising the predictive value of this clinical entity in terms of cardiovascular complications.

It has been shown that a low HDL-cholesterol in association with elevated triglyceride concentration increases the risk of cardiovascular disease. The triglycerides/HDL- cholesterol (TG/HDL-C) concentration ratio provides therefore a powerful predictor of cardiovascular disease. ⁴ Furthermore, it has been proposed that the TG/HDL-C concentration ratio is related to insulin-resistance and may assist in identifying insulin resistant individuals. It has thus been suggested that the TG/HDL-C concentration ratio might be considered as a predictor of both insulin-resistance and coronary heart disease risk. ⁵ These findings underscore the view that insulin-resistance is strongly correlated to the features of the Metabolic Syndrome but also to the cardiovascular morbidity and mortality associated with this syndrome.

Figure 2: Adjusted relative risk of death associated with the Metabolic Syndrome in men during a 11-year follow-up.

References

1. Kannel WB, McGee DL. Diabetes and cardiovascular disease: The Framingham study. JAMA 1979; 241: 2035-8.
2. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288: 2709-16.
3. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24: 683-9.
4. Gaziano JM, Hennekens CH, O'Donnell CJ, et al. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation 1997; 96: 2520-5.
5. Reaven G. Metabolic syndrome: pathophysiology and implications for management of cardiovascular disease. Circulation 2002; 106: 286-8.