August 2008
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Clinical Obesity Management to Reduce CVD Risk
Physicians express a high level of concern regarding obesity management; however, their interest in assuming this role themselves is variable.
Paul Poirier, MD, PhD, FRCP, FACC, FAHA
Obesity is a recent addition to the American Heart Association's (AHA) list of major modifiable risk factors for cardiovascular disease (CVD).1 These major risk factors include smoking, hypertension, hypercholesterolemia, obesity, diabetes, and sedentary lifestyles.2
The classic definition of obesity is shown Table 1. Calle et al3 examined the relation between body mass index (BMI) and the risk of death from all causes. They found that the association between BMI and the risk of death was substantially modified by smoking status and the presence of disease. They reported that, in healthy people who never smoked, the nadir of the curve for BMI and mortality was found at a BMI of 23.5 to 24.9 kg/m² in men and 22.0 to 23.4 kg/m² in women. Among patients with the highest BMIs, white men and women had a relative risk (RR) of death of 2.58 and 2.00, respectively, versus those with a BMI of 23.5 to 24.9 kg/m². A high BMI was most predictive of death from CVD, especially in men (RR, 2.90; 95% confidence interval [CI], 2.37–3.56). Heavier men and women in all age groups had an increased risk of death.
PREVALENCE OF OBESITY
Sturm4 reported that between 1986 and 2000, the prevalence of a self-reported BMI of ≥40 kg/m² quadrupled from about one in 200 adult Americans to one in 50, and the prevalence of a BMI of ≥50 kg/m² increased by a factor of five, from about one in 2,000 to one in 400. He also found that, in contrast, obesity based on a BMI of ≥30 mm/k² doubled during the same period, from about one in 10 to one in five. He concluded that the prevalence of clinically severe obesity is increasing much faster than obesity. "Accommodating severely obese patients will no longer be a rare event, and providers have to prepare to treat such patients on a regular basis," Sturm wrote.
In a 2006 AHA Scientific Statement,5 we reviewed the evidence of the impact of obesity on CVD, with emphasis on evaluating cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system. Important clinical and laboratory assessments that should be made in these individuals include a physical examination (blood pressure, jugular veins, cardiac auscultation), resting electrocardiogram (ECG), stress testing, cardiac echography, and cardiac catheterization if needed.
Typical cardiac symptoms among obese individuals5,6 are dyspnea with exertion and frequent, nonspecific lower extremity edema. In the SOS (Swedish Obese Subjects Study), Karason et al found that surgically induced weight loss in patients with severe obesity is associated with a marked relief in cardiac symptoms and also promotes increased leisure-time physical activity. Because cardiac dysfunction is often underestimated in these individuals, the physical examination and resting ECG are critical.
Kristeller and Hoerr conducted a mail survey of 1,222 physicians from six specialties to determine their beliefs, attitudes, and practices regarding obesity.7 The investigators found that, although physicians expressed a high level of concern for the management of obesity, their interest in assuming this role themselves was highly variable. Family practitioners, internists, and endocrinologists were more likely to report treating obese patients themselves (in 50% of patients), whereas gynecologists, cardiologists, and orthopedists were more likely to refer, treating just 5% to 29% of patients themselves. A formal referral to a weight-loss program was unlikely among family practitioners and internists, whereas endocrinologists were more likely to refer to a nutritionist. Finally, family practitioners, internists, and endocrinologists were more likely to provide counseling, give written information, make a specific plan, or schedule follow-up visits, the survey found.
METABOLIC SYNDROME
Features associated with the metabolic syndrome (ie, high-risk obesity) have an impact on many facets of a patient's health, including lifestyle risk factors, lipid profile, prothrombotic parameters, inflammatory markers, vascular components, as well as other conditions (Table 2).8 Additional comorbidities associated with obesity include coronary artery disease (CAD), heart failure, stroke, systemic hypertension, dyslipidemia, type 2 diabetes, sudden death, obstructive sleep apnea (OSA), respiratory abnormalities, pulmonary emboli, cancers, depression, gallbladder disease, osteoarthritis, and others.9
In 2002, McGill et al sought to determine the connection between obesity and the progression of coronary atherosclerosis in young people.10 They conducted the PDAY (Pathobiological Determinants of Atherosclerosis in Youth) study, which examined the arteries from more than 3,000 individuals aged 15 to 34 years who died of external causes (accidents, homicide, suicide) and were autopsied in forensic laboratories. BMI was associated with fatty streaks and raised atherosclerotic lesions in the right coronary artery (RCA) and aorta, and lesion grade and stenosis were independent of traditional risk factors. The impact of obesity (BMI >30 kg/m²) on RCA raised lesions was greater in young men with a thick panniculus adiposus (>17 mm).
Other features of the pathogenesis of CAD in obesity are:11
- endothelial dysfunction;
- increased oxidative stress;
- maximal density of macrophages/mm² in atherosclerotic lesions is associated with visceral obesity; and
- reduced coronary flow reserve is related to body fat distribution and insulin resistance.
We are now seeing adverse health outcomes in childhood obesity (Table 3), including type 2 diabetes, OSA, systemic hypertension, dyslipidemia, and metabolic syndrome. In a 2005 AHA Scientific Statement,12 Daniels et al wrote that the prevalence of overweight among children and adolescents has dramatically increased. "There may be vulnerable periods for weight gain during childhood and adolescence that also offer opportunities for prevention of overweight," they wrote. "The best approach to this problem is prevention of abnormal weight gain. Childhood and adolescent overweight is one of the most important current public health concerns."
RISK OF DEATH AND OBESITY
Mokdad et al compared major causes of death in the United States in 1990 and 200013 by conducting a comprehensive MEDLINE search that identified epidemiological, clinical, and laboratory studies linking risk behaviors and mortality. They found that the leading causes of death in 2000 were tobacco (435,000 deaths; 18.1% of total US deaths), poor diet and physical inactivity (400,000 deaths; 16.6%), and alcohol consumption (85,000 deaths; 3.5%). Although their analyses showed that smoking remains the leading cause of mortality, poor diet and physical inactivity is poised to overtake tobacco as the leading cause of death.
Yusuf et al established INTERHEART, a standardized case-control study of acute myocardial infarction (AMI) in 52 countries.14 The relationship of smoking, history of hypertension or diabetes, waist-to-hip ratio, dietary patterns, physical activity, alcohol consumption, blood apolipoproteins (Apo), and psychosocial factors to AMI were reported in 2004.
Yusuf et al found that smoking (OR 2.87 for current vs never, population-attributable risks [PAR] 35.7% for current and former vs never) raised the ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%) were significantly related to AMI (P<.0001 for all risk factors and P=.03 for alcohol).
Yusuf et al added that these associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women.
The 2006 AHA Scientific Statement5 reported that obesity was related to a doubling of the risk of premature death from sudden death and a five times higher risk of death from CVD, attributable to CAD and stroke. We have also reported ECG changes found with obesity,8 including a clinically significant increase in heart rate, QRS interval, and QTc interval, as well as false-positive criteria for inferior MI. Less clinically significant changes were increased QT dispersion, increased signal-average ECG (late potentials), increased or decreased QRS voltage, increased PR interval, ST-T abnormalities, ST depression, left-axis deviation, flattening of the T wave (inferolateral leads), and left atrial abnormalities.
Cardiac abnormalities that have been found15 in obese individuals are left ventricular (LV) diastolic dysfunction, LV hypertrophy, right ventricular hypertrophy (RV) due to pulmonary hypertension, autonomic dysfunction, arrhythmia, prolonged QTc interval, sudden death, and adipositas cordis (cardiomyopathy of obesity).
In 2003, Solymoss et al16 evaluated the incidence of the newly defined metabolic syndrome in patients with documented CAD and compared the characteristics of patients with and without the syndrome. The study was conducted among a Canadian population with CAD and included 793 men and 315 women, average age 58.1 ±9.8 years. In this population, 51% had metabolic syndrome as defined by NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) criteria.
Compared with patients without metabolic syndrome, these patients had significantly higher waist circumference, blood pressure levels, fasting glucose levels, and triglycerides but lower HDL cholesterol levels. Their homeostatic model assessment insulin-resistance index was significantly higher, with indicators of highly atherogenic, small LDL and HDL particles. They found that a family history of diabetes and the use of hypoglycemic agents, beta-blockers, and thiazides were more frequent, but physical exercise and alcohol consumption were less frequent in patients with metabolic syndrome. Cumulative coronary stenosis score and the frequency of patients with more than 50% coronary artery narrowing were higher, and there was a strong tendency for higher rates of previous MI in patients with metabolic syndrome.
OBESITY POST-MI
Lopez-Jimenez et al17 investigated the assessment of obesity as a medical problem and subsequent management recommendations among patients following AMI. Their cross-sectional analysis included a randomly selected sample of 627 patients discharged after an MI in an American academic setting in 2002 with a note regarding obesity in their chart. The mean BMI was 31 ±13 kg/m², which was documented in only 14% of patients and calculated post hoc. Waist circumference and waist-to-hip ratio were not documented at all; 83% of patients were overweight, 55% obese, and 8% were severely obese. The investigators reported that in only 20% of patients with BMI ≥30 kg/m² was the diagnosis of obesity documented either as a current medical problem, as part of past medical history, or as a final diagnosis. Dietary counseling was carried out in 61% of patients with BMI ≥25 kg/m² and in 61% of patients with BMI <25 kg/m² (P=.96). Weight loss was described as part of the goals/plan at discharge in 7% of overweight and 9% of obese patients. Lopez-Jimenez et al concluded that obesity is underrecognized, underdiagnosed, and undertreated in patients who had a recent AMI.
Modest weight loss among obese patients can be effective for lowering their risk of CVD.5 Beginning with a reduction of 250 to 500 kcal per day and a gradual increase in energy expenditure as tolerated is advised. Patients who are taking anorectic drugs should be monitored closely with regard to blood pressure.
Among this population, it is also critical to treat CHD, LVH, and RVH aggressively, as risk factors. Additional areas for focused treatment are lipids, blood pressure, diabetes, hypertension, OSA, and respiratory problems.
Antiobesity agents should be used as an adjunct to lifestyle modification with dietary therapy and physical activity.18 Drug therapy is indicated in patients with a BMI ≥30 kg/m² and in those with a BMI of ≥27 kg/m² if other risk factors or diseases are present. Surgery is indicated among patients with a BMI ≥40 kg/m² or ≥35 kg/m² with comorbidities.
Clinicians involved in the treatment of obesity have suggested a stepped-care approach to obesity management. The following steps of treatment intensity progress along with the degree of long-term weight loss needed: lifestyle intervention, hypocaloric diet, pharmacotherapy, intragastric devices (experimental), gastric pacemaker (experimental), adjustable gastric banding, Roux-en-Y gastric bypass, and finally, biliopancreatic diversion.
It is crucial that health care providers work with patients to identify potential barriers to long-term weight loss and tailor treatment approaches to the patient's individual needs. Weight loss requires an interdisciplinary approach.
Weight loss has many beneficial effects on the cardiovascular system,8 including decreased blood volume, decreased stroke volume, decreased cardiac output, decreased pulmonary capillary wedge pressure, decreased LV mass, improvement of LV diastolic and systolic dysfunction, decrease in resting heart rate, decrease in QTc interval, and an increase in heart rate variability.
Bariatric surgery should also be considered. The Prospective SOS (Swedish Obese Subjects) study19 included 4,047 patients with 10.9 years of follow-up who underwent bariatric surgery (2,037) or conventional treatment. They reported that the average weight change in control patients was <±2%. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastroplasty, 25%; and banding, 20%. After 10 years, Sjostrom et al19 found that the weight losses from baseline were stabilized at 25%, 16%, and 14%, respectively. As far as mortality data, there were 129 deaths in the control group and 101 deaths in the surgery group. The unadjusted overall hazard ratio (HR) was 0.76 in the surgery group (P=.04) versus control, and the HR adjusted for gender, age, and risk factors was 0.71 (P=.01). The most common causes of death were MI (control group, 25 patients; surgery group, 13 patients) and cancer (control group, 47; surgery group, 29). The investigators concluded that bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
CONCLUSIONS AND IMPLICATIONS
Clinicians are now being confronted more frequently with obese patients who also present with comorbidities. It is important to note that these patients frequently have ECG, heart function, and structure abnormalities. Measures of adiposity should be recorded among patients at each visit, which should include BMI, waist circumference, and waist-to-hip ratio if possible.
Finally, it is crucial that physicians identify potential barriers to long-term weight loss in order to formulate effective treatment interventions that are individualized to the patient's specific needs.
Paul Poirier, MD, PhD, FRCPC, FACC, FAHA, is an Associate Professor in the Department of Pharmacy, and a Professor of Cardiology at the University Institute of Cardiology and Pneumology, Laval University, Quebec, Canada. He may be reached at paul.poirier@crhl.ulaval.ca; or phone: 418-656-4767. Prof. Poirier would like to acknowledge that Editor-in-Chief Conni Bergmann Koury provided editorial assistance with the first draft of this article.
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