Obesity as a risk factor for cardiovascular disease.

Both cross-sectional and prospective studies have shown a close relation between excessive accumulation of body fat and premature cardiovascular morbidity and mortality. Obesity appears to increase the risk for cardiovascular disease (CVD) both directly and by promoting the occurrence of comorbid conditions, which in turn predispose patients to the development of CVD. Overweight children and adolescents are at increased risk of early death and morbidity, independently of the adult body mass index (BMI). A recent study involving 2,990 subjects followed for 57 years revealed that childhood BMI above the 75th percentile was associated with a twofold increase in the risk of ischemic heart disease compared with a BMI between the 25th and the 49th percentiles. The risk of CVD with increasing BMI is higher in young adults and seems to attenuate with aging. The impact of weight gain on the CVD risk of increasing BMI was recently emphasized in an analysis of the Nurses Health Study cohort, which showed that the relative risk of CVD morbidity and mortality increases with increasing BMI at age 18. In addition, this study demonstrated that each kilogram of weight gain from the age of 18 years was associated with a 3.1% higher relative risk of CVD. Recent studies have shown that deposition of fat in the truncal area is associated with increased CVD mortality and morbidity, independently of generalized adiposity. Although these reports pointed out that regional obesity is more predictive of an unfavorable outcome, the nature of this relation is still controversial. Metabolic and anatomic characteristics of intra-abdominal adipose tissue have been hypothesized to account for the epidemiologic observations. Bjorntorp suggested that intraperitoneal adipose tissue is responsible for the predominant effects on insulin resistance because of the higher lipolytic activity observed within in vitro studies and because of the direct drainage to the liver through the portal circulation. Although this is an attractive hypothesis, conclusive mechanistic evidence is not available. Several studies have shown that obesity, particularly truncal obesity, is often associated with lipoprotein abnormalities. Whereas elevated plasma levels of triglycerides (TGs), low plasma levels of high-density lipoprotein cholesterol (HDL-C), and qualitative changes in lowdensity lipoprotein (LDL) particles (defined as small, dense LDL) are often found in obese subjects, significant elevation of LDL cholesterol (LDL-C) levels has not been uniformly described. Kinetic studies have shown that the rate of production of very low-density lipoprotein (VLDL) is increased in obese patients. This increased VLDL production may be related to the increased turnover of free fatty acids in obesity, which stimulates the liver to synthesize more TG-enriched VLDL. Whereas some obese subjects may respond to increased VLDL production by increasing their clearance capacity for VLDL TGs, other patients develop hypertriglyceridemia. An increased concentration of circulating VLDL particles leads to an increased exchange of VLDL TGs for cholesterol esters derived from HDL and LDL. This bidirectional exchange results in a reduction in plasma HDL-C and the formation of TG-enriched and cholesterol-depleted LDL (small, dense LDL). For these reasons, although LDL-C may not be overtly increased in patients with obesity, qualitative abnormalities in LDL particles contribute to the increased atherogenic risk of obesity mediated by the lipoprotein profile. However, if an obese patient has coexisting metabolic abnormalities that may further impair LDL metabolism, frank elevation of LDL-C may occur. Some studies have also demonstrated that obese patients have higher activity of hepatic TG lipase. This mechanism may contribute to lower plasma levels of HDL-C in obesity. Obese adults have shown increased left ventricular mass, left ventricular wall thickness, and left ventricular cavity size compared with that of lean subjects. Obesity has been hypothesized to induce left ventricular hypertrophy (LVH) by various mechanisms. One important mechanism may be related to the increased circulatory blood volume of obesity, secondary to sodium and water retention. As a consequence, cardiac output increases because of an increase in stroke volume. The increase in circulating blood volume and cardiac output produces an increase in left ventricular cavity size, which produces an increase in left ventricular wall stress in accordance with Laplace’s law. The resultant increase in afterload predisposes patients to eccentric LVH. However, the development of concentric LVH has also been described in obesity, even in the absence of hypertension. We recently studied LVH in young, overtly healthy African American women using magnetic resonance imaging. Preliminary data from this study show that obesity is associated with LVH, with a significant proportion being of the concentric type. This association was found to be indepenFrom the Department of Clinical Nutrition, Center for Human Nutrition, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA. Requests for reprints should be addressed to Nicola Abate, MD, The University of Texas Southwestern Medical Center at Dallas, Center for Human Nutrition, Department of Clinical Nutrition, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9052.