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The rise in the prevalence of obesity in the United States and worldwide is threatening to undo recent advances in prevention of atherosclerotic cardiovascular disease (ASCVD). Between 1993 and 2008, the proportion of obese adults in the United States increased from 14.5% to 26.7%.1 Among the complications associated with obesity, cardiovascular events produce the greatest morbidity and mortality. A significant portion of the latter occurs in persons in whom obesity precedes type 2 diabetes. But diabetes is only one of several conditions that associate strongly with obesity. Others include dyslipidemia, hypertension, systemic inflammation, and a thrombotic tendency. Recently there has been a trend in the cardiovascular field to group all of these factors together under the heading of metabolic syndrome.2 In this sense, metabolic syndrome can be taken to represent a multiplex cardiovascular risk factor. This syndrome does not include, but is strongly associated with, other complications of obesity; for example, fatty liver, cholesterol gallstones, obstructive sleep apnea, and polycystic ovarian syndrome. The current definition generally regards hyperglycemia in the range of type 2 diabetes to be one of the components of metabolic syndrome.2,3 This is because approximately 85% of persons classified as having type 2 diabetes will meet current criteria for metabolic syndrome. Even so, many investigators in the diabetes field prefer to separate metabolic syndrome from diabetes and to view it largely as a prediabetic condition, besides being a cardiovascular risk factor.4,5 This is a semantic argument. Regardless of viewpoint, type 2 diabetes must be viewed as one of the complications of obesity and strongly associated with risk for ASCVD. This chapter focuses primarily on metabolic syndrome as a cardiovascular risk factor, with obesity being the primary exogenous factor driving its development. But other exogenous factors are further discussed, such as physical inactivity and dietary excesses, as well as endogenous susceptibility factors.


Metabolic syndrome represents a clustering of cardiovascular risk factors that are amalgamated into a single multiplex risk factor for ASCVD (Fig. 92–1).6 When the concept of metabolic syndrome was introduced into the National Cholesterol Education Program Adult Treatment Panel III Report (ATP III),2 it was considered a partner of elevated low-density lipoprotein (LDL) in the causation of cardiovascular disease (CVD). The metabolic risk factors that make up the syndrome include atherogenic dyslipidemia, elevated blood pressure, dysglycemia, a prothrombotic state, and a proinflammatory state. Several reports indicate that this clustering of metabolic risk factors cannot be explained by chance alone; hence the use of the term syndrome.7-20 This suggests that there is a common, underlying etiology of this clustering. Individuals with metabolic syndrome have an approximate doubling of risk for ASCVD and approximately four-fold higher risk for developing type 2 diabetes compared with those without the syndrome.

Figure 92–1.
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Risk factor partners: elevated low-density lipoprotein (LDL) and metabolic syndrome. The latter is ...

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