Metabolic Syndrome and Cardiovascular Risk

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The disease most studied in relation to obesity is diabetes. The precursor to type 2 diabetes and to cardiovascular disease in many patients is the metabolic syndrome. By definition, this is said to be present if three or more of the following five conditions are met:

Abdominal obesity: waist circumference >102 cm in men and >88 cm in women

• High triglyceride levels: >150 mg/dl, >1.7 mmol/L

• Low HDL cholesterol: <40 mg/dl (<1.04 mmolL) in men and <50 mg/dl (<1.30 mmol/L) in women

High blood pressure: >130/85 mmHg

• High fasting glucose: >110 mg/dl (>6.1 mmol/L)

This was the accepted definition of the metabolic syndrome until recently, and, using these criteria, a variety of studies in North America demonstrated that the syndrome was present in 21 to 33% of the population, with even higher prevalence in certain ethnic groups. A recent study (Ford et al., 2004) using the NHANES cohorts compared the prevalence of metabolic syndrome in the 1988-1994 (NHANES III) cohort with the 1999-2000 cohort. The prevalence increased overall, but particularly in women who experienced a 23.5% increase. In fact, the definition of metabolic syndrome is changing with lower cut-off points for waist circumference and for fasting glucose (>100 mg/dl, >5.6 mmol/L), meaning that an even larger proportion of the population will have the syndrome and thus be deemed to be at risk. Much of this increase will be among the elderly. Indeed, in the elderly, metabolic syndrome will be the norm, except in subjects who are underweight. So, should we be regarding it as a disease state?

In a study of over 12,000 Japanese subjects (Hasegawa et al., 2005), factor analysis was used to examine the relationship between cardiovascular risk factors. In this extensive study, the major influence of BMI was in younger subjects. Similarly, in another Japanese study involving nearly 160,000 subjects (Wakabayashi et al., 2004), the influence of BMI on blood pressure was much weaker in the elderly. The concept of the metabolic syndrome has been useful in screening populations who are at risk from diabetes and cardiovascular disease. It is important to realize, however, that susceptibility to the individual risk factors and disease states that relate to the syndrome are caused by multiple factors, not all of which relate to obesity. Around a quarter of patients with type 2 diabetes do not have the metabolic syndrome. There is no question that the accumulation of multiple risk factors places individuals at risk of morbidity and mortality from vascular disease, as shown in the recently published Casale Monteferrato Study (Bruno et al., 2004). Furthermore, development of multiple risk factors, whether or not the individual is classified as having the metabolic syndrome, is a sign of deteriorating health and is also associated with cognitive and functional decline (Crooks et al., 2003). Risk of diabetes is attenuated or accelerated by other factors such as adiponectin, high levels of which appear to confer a reduced risk of diabetes (Kanaya et al., 2004). The role of leptin, an exclusive product of adipose tissue in regulating appetite and food intake, is now well established. There is evidence that responses to leptin may become blunted in elderly subjects. This may contribute to continuing food intake in excess of requirements in individuals whose functional and exercise capacity, and therefore, calorie requirements, are decreasing as they age.

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