The clustering of cardiovascular (CV) risk factors associated with insulin is known as 'syndrome XÔÇÖ, the 'deadly quartetÔÇÖ, and 'dysmetabolic syndromeÔÇÖ among others. In addition to the clustering of obesity, hypertension (HTN), glucose intolerance, high triglycerides, and low high-density lipoprotein (HDL), other metabolic abnormalities have been associated with this syndrome, including impaired fibrinolysis and a proinflammatory diathesis. This syndrome is most commonly recognized today as metabolic syndrome (MS) and affects approximately 24% of the US adult population. According to the Third National Health and Nutrition Examination Survey (NHANES III), MS affects nearly 50 million people, including 44% of subjects over the age of 50.
MS is closely associated with obesity, which has shown a disturbing increase in prevalence, both in the US and worldwide, creating an unprecedented risk for CV disease (CVD). Obesity is prevalent across all demographic groups and is non-gender-specific. Nearly two-thirds of all adult Americans are now considered overweight or obese. Obesity is also rampant in children and adolescents, with 50% of severely obese youngsters meeting MS criteria. Pathologic studies have shown that obesity is associated with accelerated atherosclerosis in the young, with traditional risk factors accounting for only 15% of the effect of obesity on atherosclerosis. It is now estimated that the lifetime risk of developing diabetes for children born in 2000 is 33% to 39%.
MS increases the risk of CVD, even in the absence of overt diabetes mellitus (DM), with a two- to four-fold increased risk of myocardial infarction (MI) and stroke in both men and woman. The strongest association with CV events is seen with hypertriglyceridemia and low HDL cholesterol, although HTN and glucose abnormalities are also independent predictors of the prevalence of CVD. Insulin-resistant subjects have lower HDL levels and higher systolic blood pressure and triglyceride levels compared with normal subjects well before they develop diabetes, leading to the 'ticking-clockÔÇÖ hypothesis. In the Nurse Health Study, women who developed DM during follow-up had a 3.8-fold increase in risk of MI prior to their diagnosis of DM, as well as a 4.6 relative CV risk for the period after the diagnosis of DM. Diabetes is now considered a cardiovascular risk equivalent (meaning that by the time diabetes is diagnosed the patient has likely already established CVD. MS is an even more striking predictor of DM than CV events. Men with multiple features of MS have over a three-fold increased risk of CV events and a 20-fold increased risk of DM.