Obesity and Coronary Heart Disease

F many years, investigators have known that obesity is associated with increased risk of mortality, much of which is due to cardiovascular disease. I propose that a significant portion of this risk is due to specific familial disorders that are associated with both obesity and premature coronary artery disease (CAD). This hypothesis attempts to reconcile the findings of cohort studies on normal populations with studies of selected families who have specific genetic disorders and is based on the following observations: the risk of obesity for CAD has been shown by multivariate analysis to be due to other known risk factors for CAD; the association of obesity with CAD is seen in persons under 45 years of age, thus, it is premature CAD; many of the known risk factors for premature CAD are highly prevalent in families with specific genetic disorders. Many studies have used univariate analysis to show an increase in cardiovascular morbidity and mortality in obese individuals. In the large prospective screening study done by the American Cancer Society, much of the excess mortality rates in persons of higher than average weight was due to CAD. There was a stepwise increase in CAD for each weight index category. Larsson et al. reviewed numerous studies that confirm the univariate association between obesity and CAD. While body weight may be related to the risk for premature cardiovascular disease, it has also been shown to be associated with most of the known risk factors for atherosclerosis, such as hypertension, cigarette smoking, low levels of high density lipoprotein (HDL) cholesterol, elevated plasma glucose levels, hypercholesterolemia, and hypertriglyceridemia. When multivariate analysis is used to consider all of these additional risk factors, the relationship between obesity and coronary heart disease is markedly attenuated or disappears entirely. The Framingham Study reported that after 26 years obesity was a significant predictor for coronary disease. This risk was independent of age, total cholesterol, systolic blood pressure, cigarette smoking, and glucose intolerance; however, plasma triglyceride and HDL cholesterol were not assessed. It is difficult to interpret multivariate analyses of CAD risk factors, which assume independence of variables, when many of these risk factors are obviously interdependent. Elevated systolic and diastolic blood pressure appear to be associated with an increased risk for CAD at all ages and are also more prevalent in the obese. Similarly, cigarette smoking is associated with a marked increase in CAD at all ages. This association is complex, however, because smokers weigh less than nonsmokers and the effect of cigarette smoking on CAD risk may be reversible when smoking is stopped. Decreased HDL cholesterol levels are also associated with an increased risk for CAD in all age groups, and HDL cholesterol levels are lower in the obese. Elevated total plasma cholesterol levels are, similarly, related to premature CAD, and the obese have higher levels also. Elevated fasting plasma glucose levels are a risk factor for premature CAD and are seen in the obese individual with noninsulin-dependent diabetes mellitus. Finally, in some studies hypertriglyceridemia is associated with premature CAD, and obesity is also associated with elevated plasma triglyceride levels. Thus, it may be argued that obesity is not an important independent risk factor for premature CAD because of the relationships between obesity and other CAD risk factors. However, weight loss does bring a normalization of blood pressure, increased HDL cholesterol levels, and lower plasma glucose cholesterol and trigly-