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CARDIOLOGY CASEBOOK |
Case 1
A 63-year-old Mexican-American woman presents to the emergency department stating that for the past several nights she has had to sleep sitting up in a reclining chair because of difficulty breathing when lying in bed. She also reports that her legs have been swollen lately. She had no other complaints and no history of hypertension or diabetes. On physical examination, her height was 5 ft 3 in (1.5 m), weight 250 pounds (112.5 kg) and blood pressure 130/80 mm Hg. Rales were heard at the bases of her lungs; heart rate was 96 beats/minute, there was an S3 and S4 gallop and a grade 2/6 mid to late systolic mitral valve murmur. She had 2+ pretibial and ankle pitting edema. A lipid profile showed levels all within the American Heart Association/American College of Cardiology guidelines. An electrocardiogram revealed evidence of left ventricular hypertrophy with repolarization changes. An echocardiogram revealed left ventricular hypertrophy and dilatation and mild to moderate mitral regurgitant flow.
QUESTIONS
Case II
A 45-year-old white man presents to his primary healthcare provider for a routine physical examination. He has no complaints and considers himself to be in good health. On physical examination his height was 5 ft 10 in (1.78 m), weight 220 pounds (99 kg), and blood pressure 155/95 mm Hg. The remainder of the examination was unremarkable. His blood work revealed a fasting blood sugar of 160 mg/dL (8.9 mmol/L), hemoglobin A1C 8.1%, cholesterol 265 mg/dL (6.85 mmol/L), high-density lipoprotein (HDL) 35 mg/dL (0.91 mmol/L), low-density lipoprotein (LDL) 185 mg/dL (4.78 mol/L), triglycerides 250 mg/dL (2.82 mmol/L), and very low density lipoprotein (VLDL) 52 mg/dL (1.34 mmol/L). Results of liver and renal function tests were within the normal range. The urine was positive for albumin. A diagnosis of the metabolic syndrome was made. A low-calorie, low in sodium, cholesterol, and carbohydrates diet was ordered, in addition to an exercise regimen. The recommended medications were a statin, a diuretic, an angiotensin-converting enzyme inhibitor, a ß-blocker, and an oral hypoglycemic agent (metformin). He had heard the news about leptin, a fat hormone, and asked whether this new hormone could help him lose weight.
QUESTIONS
ANSWERS
Case 1
1. d. 61%
Obesity is currently the focus of public health officials because of the alarming rate of increase in the number of overweight people in all age groups in the United States. Obesity is reaching epidemic proportions in the United States; statistically we are the fattest country in the world. Obesity is defined by the BMI, as weight in kilograms divided by the square of the height in meters (kg/m2). The World Health Organization (WHO) classifies overweight as a BMI greater than or equal to 25, obesity as a BMI greater than or equal to 30, and extreme obesity as a BMI greater than or equal to 40. Studies by the National Health and Nutritional Examination Center has shown an upper trend in the prevalence of obesity in the adult populations, particularly in the past 20 years. It is estimated that 61% of adults in the United States (20 to 74 years) are either obese or overweight, 27% are obese, and 34% are overweight.1,2 There is a frightening obesity trend in young American children, which should be a wake-up call to a public health problem that we will be facing 10 to 50 years from now when these youngsters become old enough to be at risk of CAD, heart failure, and stroke. In the past 2 decades, the prevalence of obesity has doubled in children and tripled among adolescents. Among children 6 to 11 years old 13% are overweight, and among children 12 to 19 years old 14% are overweight. The increase in obesity has been more dramatic in black and Mexican American children and adolescents: about 70% of obese preadolescent children remain obese as adults.3
2. a. waist circumference
Although the association of obesity to CV risk factors such as type II diabetes mellitus, hypertension, and hyperlipidemia is well known, it is puzzling that some very obese persons have normal blood pressures and normal blood glucose levels and lipid profiles. Part of the problem may be related to the method used to measure obesity. It is currently recognized that body fat distribution has important health implications. Central abdominal adiposity has a stronger association with CV risk factors than peripheral obesity and is more predictive of coronary events. Since an accurate measurement of body fat is both costly and impractical, most studies have used the BMI as a surrogate measurement. Although the BMI is a fairly accurate representation of the degree of obesity, the relation between BMI and adipose tissue mass in women differs from that in men and varies with age. In addition, BMI does not convey information on body size.4 Other studies have used the WHR as an index of visceral adiposity. However, WHR predicts visceral adipose tissue volume with an error of at least 15% to 20%. Some authors consider waist circumference as the best predictor of the absolute amount of visceral adipose tissue and find it preferable to WHR measurement.5 A waist circumference measure exceeding 90 cm, associated with a high triglyceride level, has been implicated in the risk forms of abdominal visceral obesity.
3. d. all of the above
The role of obesity as an independent risk factor for CAD and other CV problems has been debated. The Framingham Study indicated that the deleterious CV effects seen with obesity could be explained by coexisting conditions frequently present in obese persons, such as diabetes mellitus, hypertension, and dyslipidemia. Recent studies in men, however, indicate that obesity is an independent risk factor for CAD, CHF, and stroke.4,6 Obesity is frequently associated with left ventricular hypertrophy and dilatation. The Framingham Heart Study also showed that an elevated BMI was associated with an increase risk of heart failure, independent of other risk factors and estimated that 11% to 14% of cases of heart failure in the community could be attributed to obesity alone.2,7 However it should be noted that abdominal obesity is strongly associated with accelerated coronary atherosclerosis and type II diabetes mellitus in adolescents and young adult men as well as in women.7,8 In another recent study,2 obesity alone was reported to account for 11% of CHF in men and 14% in women.
4. e. all of the above
It is now well accepted that inflammation is a major component of unstable atherosclerosis. Adipose tissue previously thought of as lipid storage is now recognized as a source of inflammatory mediators (cytokines such as tumor necrosis factor and interleukin-6). The elevation of hs-CRP levels in obesity reflects the enhanced production of cytokines which may render otherwise stable atherosclerotic plaques unstable and thus susceptible to rupture.6 The prothrombotic effect manifested by increased production of PAI-1 not only plays a role in coronary thrombosis, but also increases the risk of stroke and pulmonary embolism seen in obese persons.6 A recently published study has shown that women with abdominal obesity have increased lipid peroxidation and thromboxane (TXA2)-dependent platelet activation. This represents a novel mechanism linking obesity to CV risks. In addition, obese persons have enhanced activation of the sympathetic nervous system, which could also play a role in the increased morbidity and mortality seen in that group.9
Case 2
5. f. all of the above
Frequently obesity-associated dyslipidemia is a factor seen in the metabolic syndrome, a cluster of clinical abnormalities that includes insulin resistance obesity, hypertension, dyslipidemia, and microalbuminuria. The metabolic syndrome affects 23% of the Western world. Eighty percent of patients with the metabolic syndrome have type II diabetes mellitus. These patients present with a particularly atherogenic type of hyperlipidemia, that is, elevated fasting triglyceride levels and low levels of HDL cholesterol. The clinical importance of the metabolic syndrome resides in its putative effects on CV mortality. The metabolic syndrome is a major risk factor for CV events and a precursor of heart failure. The prevalence of CAD, myocardial infarction, and stroke is 3 times greater in patients with the metabolic syndrome.10,11
6. b. angiotensin II
c. leptin
Our understanding of the physiological mechanisms leading to obesity were greatly enhanced by the discovery of the hormone leptin (after leptos Greek for thin). Leptin, a protein produced by fat cells, is important in the regulation of body fat. Leptin acts on receptors in the hypothalamus, counteracting the effect of feeding stimulants, thus suppressing appetite.12 It also acts directly on the cells of the liver and skeletal muscle, reducing the storage of fat in these tissues. Ninety-five percent of obese people have high levels of circulating leptin, indicating leptin resistance. A small minority of obese persons with low leptin levels will respond to leptin treatment by losing significant amounts of weight.13 There is much more to be learned about the physiological mechanisms leading to leptin secretion, its relationship to caloric balance, and the effects of this hormone on the heart and peripheral tissues. The clinical significance of adipocite (fat cell) secretion of angiotensin II is currently under investigation.6 Angiotensinogen and angiotensin II are also derived from adipocytes. This is of particular interest because the renin-angiotensin-aldosterone system plays a major role in the pathophysiology of hypertension, which can result in cardiac hypertrophy, diastolic dysfunction, and heart failure.
7. e. all of the above
Sustained weight reduction has a number of health benefits, including a decrease in total cholesterol, LDL-cholesterol, and triglyceride levels and an increase in HDL-cholesterol level. Approximately 50% of obese persons who lose weight have a reduction in blood pressure, often to normal levels. Other benefits observed include the following: (a) reduction in the left ventricular mass in young overweight hypertensive persons, (b) decrease in plasma norepinephrine and renin activity indicating suppression of sympathetic nervous activity, (c) increased glucose tolerance and insulin sensitivity, and (d) reduction in PAI-1 and factor VII levels.14
SUMMARY
The prevalence of marked obesity is increasing rapidly among adults and has more than doubled in 10 years. Sixty-one percent of the adult population of the United States is overweight or obese. Americans are the fattest people on earth. Paradoxically these increases in the numbers of persons who are obese or overweight have occurred during recent years when Americans have been preoccupied with numerous dietary programs, diet products, weight control, health clubs, home exercise equipment, and physical fitness videos, each "guaranteed" to bring rapid results. Overweight and obesity are also world problems. The World Health Organization estimates that 1 billion people around the world are now overweight or obese. Westernization of diets has been part of the problem. Fruits, vegetables, and whole grains are being replaced by readily accessible foods high in saturated fat, sugar, and refined carbohydrates. Since class 3 obesity (morbid or extreme obesity) is associated with the most severe health complications, the incidence of hypertension, stroke, heart disease, diabetes, and peripheral vascular disease will increase substantially in the future.
Recently, obesity alone has been implicated in the development of cardiac hypertrophy and CHF. The metabolic syndrome associated with abdominal obesity, which includes insulin resistance, dyslipidemia, and elevated CRP levels, identifies subjects who have an increase in cardiovascular morbidity and mortality. Twenty to 25% of the adult population in the United States have the metabolic syndrome, and in some older groups this prevalence approaches 50%.
The prevalence of overweight children in the United States has also been increasing dramatically, especially among non-Hispanic blacks and Mexican-American adolescents. Overweight children usually become overweight adults. Atherosclerosis begins in childhood. The degree of atherosclerotic changes in children and young adults can be correlated with the presence of the same risk factors seen in adults. As health providers, our direction is obvious!
ACKNOWLEDGMENT
Supported in part by a grant from the Applebaum Foundation, in loving memory of Joseph Applebaum.
Reprint requests: Louis Lemberg, MD, University of Miami School of Medicine, Division of Cardiology (D-39), P O Box 016960, Miami, Fla 33101.
Bonow RO, Smaha LA, Smith SC Jr, et al. World Heart Day 2002. The international burden of cardiovascular disease: responding to the emerging global epidemic. Circulation. 2002;106:1602–1605.
Cooke JP, Oka RK. Does leptin cause vascular disease? Circulation. 2002;106:1904–1905.
Field AE, Coakley EH, Must A, et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med. 2001;161:1581–1586.
Fontanarosa PB. Obesity research: a call for papers (editorial). JAMA. 2002;288:1772–1773.
Freedman DS, Khan LK, Serdula MK, et al. Trends and correlates of class 3 obesity in the United States from 1990 through 2000. JAMA. 2002;288:1758–1761.
Janssen I, Katzmarzyk PT, Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health Guidelines. Arch Intern Med. 2002;162:2074–2079.
Narbro K, Agren G, Jonsson E, et al. Pharmaceutical costs in obese individuals. Arch Intern Med. 2002;162:2061–2069.
Wilson PWF, D’Agostino RB, Sullivan L, et al. Overweight and obesity as determinants of cardiovascular risk. Arch Intern Med. 2002;162:1867–1872.
Wylie-Rosett J. Fat substitutes and health. An advisory from the nutrition committee of the American Heart Association. Circulation. 2002;105:2800–2804.
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