The incidence of obesity started growing to epidemic proportions in the 1980s. Currently more than 30% of the US population is obese (body mass index [BMI] ≥30) and nearly two thirds are overweight (BMI between 25 and 29.9). These figures are expected to rise further if the current trend continues. There are 2 distinct genetic mechanisms involved in obesity. One is caused by the infrequent presence of certain genes, which produce rare syndromes associated with significant obesity. However, obesity is much more commonly mediated by the presence of other “susceptibility” genes. More than 41 such genetic sites have been identified and in their presence obesity will develop only if there is a favorable environment. These genes control different processes, such as regulation of fat distribution, metabolic rate, response to exercise and diet, control of feeding, and food preferences, etc. But the striking rise in the incidence of obesity, which has happened in the last few decades, is not because of changes in the genetic background of the human race, since these changes take thousands of years to evolve. This “epidemic” is mainly caused by rapid lifestyle changes involving eating habits and exercise.
There is an increase in the incidence of sudden cardiac death and arrhythmias in obesity.24 Fatal arrhythmias may be the most frequent cause of death among obese patients. According to the Framingham data, sudden cardiac death was 40 times higher in obese men and women.24 In another study of severely obese individuals, this was 6-fold and 12-fold higher in those aged 25 to 34 years and 35 to 44 years, respectively.25 In the NHANES III study, 30% of obese patients with glucose intolerance had a prolonged corrected QT (QTc) interval. Schouten et al26 found that 8% of obese individuals had a QTc interval of more than 0.44 seconds and, in 2%, it was more than 0.46 seconds. A QTc interval of more than 0.42 seconds was associated with increased mortality in “healthy” obese patients followed for 15 years. QT dispersion, which measures the difference in duration between the maximum and the minimum QT interval in different leads in the EKG is a good noninvasive measurement for quantifying the degree of myocardial repolarization inhomogeneity, which was also increased in the obese. Both QTc interval and QT dispersion are mediated by changes in sympathetic-vagal balance. Catecholamine levels are increased in the obese.27 In addition, increased free fatty acid levels in the obese may also affect repolarization. In patients with myocardial infarction, there is a relation between ventricular arrhythmias and long-chain saturated fatty acid level. Various changes occur in the autonomic system with weight gain. A 10% increase in body weight causes a decrease in parasympathetic tone and increase in heart rate. On the other hand, heart rate decreases with weight reduction. There is a significant improvement in heart rate variability with 10% weight loss. Both increased resting heart rate and decreased heart rate variability are predictors of mortality, independent of the ejection fraction.
In a study of obese patients without clinical heart disease, the prevalence of late potentials (high-frequency, low-amplitude signals at the terminal part of the QRS complex demonstrated using high-resolution signal averaged recording) are seen to be increased proportionately with BMI. The presence of late potentials has been documented to be associated with increased risk of ventricular arrhythmias in several cardiac conditions and is present in less than 3% of normal controls. In those with a BMI score between 31 to 40, 41 to 50, and >50, the incidence of late potentials were 35%, 86% and 100%, respectively. This increased frequency may be related to fat and mononuclear infiltration, fibrosis, focal myocardial disarray, or myocyte hypertrophy.
Coronary Artery Disease
Obesity is an independent predictor of coronary artery disease, as observed in the Framingham heart study,30 Manitoba study,31 and Harvard public health nurses study.32 In the Framingham cohort, patients aged 28 to 62 years were followed for a mean of 26 years. Among men younger than 50 years, the heaviest group experienced twice the risk of coronary disease compared with the leanest group. The risk was increased 2.4-fold among obese women of similar age, and this was after adjusting for the influence of other major cardiovascular risk factors.30 Autopsy among 15 to 34 year olds who died from accidental causes revealed plaques and ulceration in the coronary arteries and abdominal aorta, the extent of which correlated with the amount of abdominal fat and BMI (PDAY study). Obesity accelerates atherosclerosis decades before clinical manifestations appear and this remained significant even after adjustment of other risk factors like high cholesterol, hypertension, smoking, and increased HbA1c. The density of macrophages per mm2 of plaques also correlated with visceral obesity.
After coronary artery bypass surgery also there are more adverse outcomes in obese patients.34 They have increased incidence of postoperative thromboembolism, infections of the sternum, and saphenous vein harvest sites. There is also a higher incidence of atrial arrhythmias.34 However mortality or postoperative cerebrovascular events were not significantly higher. Even pulmonary complications were comparable, except in the severely obese (BMI >35) and when complicated by diabetes, renal dysfunction or age >60.
Among men, the prevalence of hypertension is 15% in those with BMI <25 and 42% if BMI is >30; in women, these are 15% and 38%, respectively. Blood pressure is the product of cardiac output and systemic vascular resistance, and cardiac output is increased in obese patients because of increased blood flow to the adipose tissue.15 We should expect the systemic vascular resistance to be low in obese individuals because of the increased cross-sectional area of the vascular bed. However, it is often inappropriately normal or even high, and this increases the likelihood of hypertension. Various factors like low-grade inflammation mediated through adipokines, hyperinsulinemia, and insulin resistance, over-activity of the sympathetic nervous system and a disordered sleep pattern increase the systemic vascular resistance in obese patients.37 With increasing severity of obesity, hypertension becomes more prevalent. It may initially be diurnal, especially if there is coexisting sleep apnea.
On the right side also there is an increase in the filling pressures, systolic pressure, and pulmonary vascular resistance. Increased pulmonary vascular resistance may be because of a combination of intrinsic pulmonary disease, sleep apnea/hypoventilation, recurrent pulmonary thromboembolism, or left ventricular dysfunction, all of which are more common in obese individuals. Pulmonary artery pressure is elevated in more than 50% of obese patients but usually only to a mild degree.19 Fifteen percent to 20% of patients with obstructive sleep apnea have pulmonary hypertension. This is often mild and ranges from 30 to 35 mm Hg and is rare in the absence of daytime hypoxia. EKG signs of right ventricular overload are very late manifestations. Nocturnal dysrhythmias, right and left heart failure, myocardial infarction, stroke, and mortality are more common in those with obstructive sleep apnea .
Increased BMI and waist–hip ratio are independent risk factors for stroke, even after adjusting for hypertension, hypercholesterolemia, and diabetes. In the prospective Physician’s Health study cohort of 21,414 men, those patients with BMI between 25 and 30 (8,105 men) and >30 (1,184 men) had a multiple adjusted relative risk of total stroke of 1.32 (95% CI, 1.14–1.54) and 1.91 (95% CI, 1.45–2.52), respectively, compared with men with BMI <25. In these groups the relative risk of ischemic stroke was 1.35 (95% CI, 1.15–1.59) and 1.87 (95% CI, 1.38–2.54) and hemorrhagic stroke was 1.25 (95% CI, 0.84–1.88) and 1.92 (95% CI, 0.94–3.93), respectively. With each 1-unit increase in BMI score, the multiple adjusted rate of ischemic stroke increased by 4% and 6% for hemorrhagic stroke. The underlying mechanisms by which increased BMI score affects stroke risk, independent of established risk factors such as hypertension and diabetes, is not fully understood. This could be mediated by the prothrombotic (higher levels of plasminogen activator inhibitor-1 antigen and activity, fibrinogen, von Willebrand factor, and factor VII) and proinflammatory state (increased levels of C-reactive protein and lymphokines) in obesity.
Obesity and Coronary Heart Disease
Until recently the relation between obesity and coronary heart disease was viewed as indirect, ie, through covariates related to both obesity and coronary heart disease risk, including hypertension; dyslipidemia, particularly reductions in HDL cholesterol; and impaired glucose tolerance or non–insulin-dependent diabetes mellitus. Insulin resistance and accompanying hyperinsulinemia are typically associated with these comorbidities. Although most of the comorbidities relating obesity to coronary artery disease increase as BMI increases, they also relate to body fat distribution. Long-term longitudinal studies, however, indicate that obesity as such not only relates to but independently predicts coronary atherosclerosis. This relation appears to exist for both men and women with minimal increases in BMI. In a 14-year prospective study, middle-aged women with a BMI >23 but <25 had a 50% increase in risk of nonfatal or fatal coronary heart disease, and men aged 40 to 65 years with a BMI >25 but <29 had a 72% increased risk. The overall relation between obesity and coronary artery disease morbidity and mortality is less clear for Hispanics, Pima Indians, and African-American women.
Congestive Heart Failure
Left ventricular hypertrophy is common in patients with obesity and to some extent is related to systemic hypertension. However, abnormalities in left ventricular mass and function also occur in the absence of hypertension and may be related to the severity of obesity. Hypertension is approximately three times more common in obese than normal-weight persons. This relationship may be cause-and-effect in that when weight increases, so does blood pressure, whereas when weight decreases, blood pressure falls.
Increased left ventricular volume and wall stress in addition to increased stroke volume and cardiac output are commonly seen in systemic hypertension. The hypertrophy of the left ventricle is both concentric and eccentric, and diastolic dysfunction is common. When obesity is present but systemic hypertension is absent, left ventricular volume is often increased, but wall stress usually remains normal. However, in obese patients without hypertension, increases in stroke volume and cardiac output as well as diastolic dysfunction are seen. These changes in the left ventricle are related to sudden death in obese patients. When 22 patients with severe obesity were examined postmortem, dilated cardiomyopathy was most frequently associated with sudden death (n=10), with severe coronary atherosclerosis (n=6), concentric left ventricular hypertrophy without dilatation (n=4), pulmonary embolism (n=1), and hypoplastic coronary arteries (n=1) also found. Thus, dilated cardiomyopathies, presumably with concomitant cardiac arrhythmias, may be the most common cause of sudden death in patients with severe obesity. The prolonged QT interval also seen in obesity may predispose to such arrhythmias.
Changes in the right heart also occur in obesity. The pathophysiology is related to obstructive sleep apnea and/or the obesity hypoventilation syndrome, which produce pulmonary hypertension and right ventricular hypertrophy, dilatation, progressive dysfunction, and finally failure. However, right ventricular dysfunction can also occur as a consequence of left ventricular dysfunction, and the heart failure that develops is often biventricular.
Treatment of Obesity and Heart Disease
In patients with congestive heart failure, sodium restriction and small reductions in weight may dramatically improve ventricular function and oxygenation. In addition, several studies suggest that the more extensive weight reduction that follows gastrointestinal surgery for obesity reduces cardiovascular mortality and in persons with non–insulin-dependent diabetes, both cardiovascular and total mortality. Moreover, although many studies have demonstrated the beneficial effects of weight reduction on cardiovascular risk factors such as hypertension and dyslipidemia, recent studies from Sweden indicate that the major reduction of body weight that follows gastrointestinal surgery for obesity also reduces incidence of non–insulin-dependent diabetes mellitus. Shortening of the QT interval also follows weight reduction. Thus, weight reduction appears efficacious in reducing risks of coronary heart disease and congestive heart failure and potentially preventing heart disease in obese patients.
Treatment of obesity should be based on its severity and the presence of comorbidities, eg, congestive heart failure, dyslipidemia, hypertension, non–insulin dependent diabetes, and obstructive sleep apnea. Maintaining a BMI <25 throughout adult life has been recently recommended. For most patients with a BMI between 25 and 30, lifestyle modifications including diet and exercise are appropriate. Diets should be modestly restricted in calories; evidence suggests that obese patients who have slower rates of weight reduction have the same long-term outcomes as patients undergoing more rapid weight reduction. Restricting consumption of fat to <30% of total calories should also be prescribed because low-fat diets may also promote weight reduction. When rapid weight loss is needed, eg, for severe biventricular heart failure, more severe caloric restriction, eg, ≤800 calories daily, with at least 0.75 g/kg bioavailable protein, can be used. For less-urgent weight reduction, a loss of 0.45 kg (1 lb) per week is reasonable. This rate of weight loss would require a caloric deficit of about 400 calories per day.
Training programs that increase physical activity have had a variable effect on body mass and composition. However, simply changing daily routines, eg, parking farther away and using the stairs rather than the elevator, may also be effective. Once weight loss has been achieved, a more vigorous exercise program may also enhance maintenance of reduction in weight.
Pharmaceuticals should be considered with a BMI >30 or with less-severe obesity and comorbidities. The rationale for use and discussion with the patient about adverse effects of the medications should be documented in the patient’s record. If the risk from obesity is sufficiently serious to indicate use of antiobesity drugs, long-term use should be anticipated. However, a case-control study in Europe demonstrated that patients treated with dexfenfluramine for more than 3 months had an odds ratio of 23.1 (95% confidence interval, 6.9 to 77.7) of developing primary pulmonary hypertension. A potential link between fenfluramine therapy of obese patients with valvular heart disease has also been raised. As a result, both fenfluramine and dexfenfluramine have been withdrawn from the market. Few drug choices remain. Like other nonsurgical therapies for obesity, once antiobesity drugs are discontinued, weight gain typically follows.
When the BMI is >35 and comorbidities exist, gastrointestinal surgery becomes a consideration. When the BMI is >40, surgery is the treatment of choice. The experience of the surgeon and type of operation chosen predict outcome. In general, a Roux-en-Y gastric bypass is superior to gastric plication.
Although weight reduction is not recommended for patients with a BMI <25, some patients in this category clearly have risks related to body fat distribution. Although measurement of waist circumference may help identify such patients, this assessment is crude, and other approaches are more expensive, ie, magnetic resonance imaging and computed tomography. Moreover, the radiation risk with some techniques (eg, computed tomography) precludes their use in children.
No matter what the therapeutic approach, it is important to realize that obesity is a disorder and recidivism is common, with <5% of patients maintaining their reduced weight at 4 years. Thus, therapeutic regimens must be maintained indefinitely; even then, only surgery has been proved to produce substantial sustained long-term weight loss. Prevention of obesity by diet and regular physical activity remains the highest priority for maintaining cardiovascular health. This is particularly important for small children and adolescents.