Waist Circumference, Visceral Obesity, and Cardiovascular Risk

Populations of industrialized countries are becoming more overweight as a result of deleterious changes in lifestyle, and obesity is expected to become the most common health problem of the 21st century.1 Obesity is associated with an increased risk of morbidity and mortality, and with reduced life expectancy.2-4 Moreover, obesity is becoming the major driving force responsible for the increased prevalence of cardiovascular disease (CVD) in the developed world. This chronic noncommunicable disease is therefore a major contributor to the global burden of disease and disability associated with numerous conditions such as coronary artery disease (CAD), stroke, hypertension, dyslipidemia, type 2 diabetes mellitus, osteoarthritis, pulmonary embolism, respiratory abnormalities and sleep apnea.1,5 Yet only recently has obesity been given the same level of attention as other risk factors for CAD5 and recognized as largely responsible for the prevalence of diseases worldwide in the near future6 (Table 1). Accordingly, the American Heart Association has stated that obesity is a major modifiable risk factor for heart disease.7,8 This review discusses the importance of visceral obesity as a health risk from a cardiovascular prevention and cardiac rehabilitation perspective.Table 1: • THE WORLDWIDE 5 LEADING CAUSES OF DISEASE BURDEN MEASURED IN DISABILITY ADJUSTED LIFE YEARS FOR THE PERIOD 1990 TO 2020EPIDEMIOLOGY The prevalence of obesity in the United States has increased steadily over the past 40 years.9 In industrialized countries, this scourge has reached epidemic proportions.10-13 For instance, within the past 10 years, the percentage of overweight and obese individuals in North America and in some countries in Europe has increased to more than 50% of adults age 20 years or older.9,11 Accordingly, among the 9405 patients evaluated at the Duke University cardiac catheterization laboratory, the prevalence of obesity has increased from 20% to 33% in only 10 years (1986 to 1997).14 In the catheterization laboratory, obesity was associated with younger age and more comorbidities, but with singlevessel disease at baseline.14-16 Obesity also was associated with more clinical events over the 30-day period after cardiac catheterization, with higher cumulative inpatient medical costs and significant differences in unadjusted survival at 10 years.14 It also has been reported that overweight and obese patients are highly prevalent (88%) in cardiac rehabilitation programs.17 Therefore, although some studies have questioned the contribution of obesity to clinical outcomes among patients undergoing angiography,15,16 the recognition of obesity as a health problem is critical in the context of a cardiac prevention and rehabilitation program aimed at preventing a first or recurrent CAD event. DEFINITION OF OBESITY According to national and international guidelines, an overweight condition is defined as a body mass index (BMI: weight in kilograms divided by the square of the height in meters) of 25 to 29.9 kg/m2, and obesity is defined as a BMI of 30 kg/m2 or more.10 On that basis, all overweight and obese adults older than 18 years with a BMI of 25 kg/m2 or more are assumed to be at risk for the development of cardiovascular co-morbidities.1 However, BMI does not account for the wide variation in body fat distribution, does not address the etiologic factors leading to obesity across different individuals and populations, and does not relate body composition and body size to health outcomes. Although obesity per se is considered a major modifiable risk factor for ischemic heart disease,7,8 it is of clinical importance to keep in mind that a remarkable heterogeneity exists among obese subjects, and that the presence of visceral obesity generally worsens the “metabolic portrait,” which is associated with a cluster of traditional and nontraditional risk factors: an atherogenic dyslipidemic state, hypertension, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, and a prothrombotic and inflammatory state. These abnormalities all are potentially synergistic and deleterious in increasing congestive heart disease (CHD) risk.5,18 Thus, an abundant literature published over the past 20 years has emphasized that abdominal obesity is more important than excess fat as a correlate of the complications previously regarded as the consequence of obesity per se.19-22 Because not all obese individuals are at increased risk of CVD, the challenge for the clinician in preventive cardiology is to identify the subgroup of obese patients who are “at risk” for CVD (ie, obese patients characterized by the atherogenic cluster of metabolic abnormalities referred to as the “metabolic syndrome”). In addition to its well-documented role in lipid storage and mobilization, adipose tissue is a major site of cytokine production, which also may play a role in the atherosclerotic process, increasing the risk of an acute coronary syndrome. Figure 1 presents a list of molecules produced by adipose tissue that could be involved in atherosclerosis. In this regard, it has been reported in a recent study that plasma C-reactive protein levels are associated positively with both total fatness and excess visceral adipose tissue accumulation and negatively with insulin sensitivity and that weight loss reduces C-reactive protein levels significantly,23 a relevant finding from a cardiac rehabilitation perspective. For this reason, adipose tissue may modulate the predisposition to an acute coronary syndrome through the production of a chronic proinflammatory state.24-30 Although this is beyond the scope of this article, there are also additional clinically significant cardiac adaptations associated with obesity. Some of these changes are listed in Figures 2 and 3.Figure 1.: Peptide and nonpeptide compounds synthesized and released into the bloodstream by adipose tissue.Figure 2.: Heart adaptations to obesity.Figure 3.: Clinically significant electrocardiograph changes associated with obesity. SAECG, signal-averaged electrocardiogram.DEFINITION OF THE METABOLIC SYNDROME (OBESITY “AT RISK”) Because not all obese individuals are at increased risk for CVD, the challenge for the clinician is to have access to simple screening tools to identify the obese patients “at risk” (ie, the obese state associated with the presence of the metabolic syndrome). The criteria established by the National Cholesterol Education Program31 suggests that metabolic syndrome can be identified by at least three of the following variables: waist circumference exceeding 102 cm for men and exceeding 88 cm for women, fasting triglycerides of 150 mg/dL or more (≥1.7 mmol/L), HDL cholesterol less than 40 mg/dL (6.94 mmol/L).32 In a different analysis of the same data set (NHANES III), Janssen et al33 reported that the health risk was increased among individuals with an elevated waist circumference, even among normal-weight subjects. There is ample evidence supporting the concept that the presence of excess abdominal fat in proportion to total body fat is an independent predictor of type 2 diabetes and CVD.34-36 Accordingly, the features of the metabolic syndrome are most often the consequence of excessively accumulated abdominal fat, especially when accompanied by a high accumulation of visceral adipose tissue.37-41 This profile is accompanied by a prothrombotic, proinflammatory state,42-46 and an abdominal distribution of body fat is associated with abnormal plasma levels of numerous molecules24-26,47-50 (Figure 4). This hypercoagulable state, which accompanies excessive central fat deposition, also may be associated with impaired endothelial function.51,52 Therefore, the abdominally obese patient with the features of the metabolic syndrome is characterized by an atherogenic, prothrombotic, inflammatory profile (Figure 4), which may substantially increase the risk of an acute coronary syndrome.28,53 Indeed, abdominal obesity, as assessed by waist circumference (independently of ethnicity, gender, smoking status, and age), is associated with increased total healthcare expenditures, especially with the costs of inpatient care. Thus, waist girth may be a better predictor of healthcare costs than the widely used BMI.54Figure 4.: Cluster of atherogenic metabolic abnormalities associated with obesity.Thus, the clinician should give careful attention to the abdominally obese patient with the metabolic syndrome (Figure 5) because this is a highly prevalent cause of CHD.55 Indeed, it has been reported that the metabolic syndrome may be present in approximately 10% of the subjects with a normal glucose tolerance test, in approximately 50% of the subjects with dysglycemia (impaired fasting glucose/impaired glucose tolerance), and in at least 80% of those with type 2 diabetes.56,57 From an epidemiologic perspective, a recent report indicated that 20% to 25% of the adult US population could have the metabolic syndrome.58 Prospective evidence shows that after only 4-years of follow-up evaluation, abdominal obesity is associated with accelerated progression of carotid atherosclerosis in men independently of overall obesity and other risk factors.59 This association between abdominal obesity and carotid atherosclerosis was found to be particularly evident when accompanied by a serum apolipoprotein B level of 1.01 g/L or more that translates into smaller dense LDL.59 Because visceral obesity is not commonly associated with elevated LDL cholesterol, measurement of apolipoprotein B and LDL size eventually may become crucial for the assessment and management of CHD risk among patients with abdominal obesity.60Figure 5.: Simplified model showing that a sedentary lifestyle combined with a diet of poor nutritional value may lead to the development of obesity. In the presence of unknown genetic susceptibility factors, a high-risk obesity phenotype will develop leading to a dysmetabolic profile with atherogenic, prothrombotic and inflammatory abnormalities favoring not only the progression of CAD but also increasing the risk of an acute coronary syndrome. AT: adipose tissue; CAD: coronary artery disease. CRP, C-reactive protein; IL-6, interleukin-6; FFA, free fatty acid; PAI-1, plasminogen activator inhibitor-1; TG, triglycerides; TNF-α, tumor necrosis factor-α.Findings have shown the cardiovascular mortality associated with the metabolic syndrome to be substantially increased (12.0% vs 2.2%) in 3606 subjects with a median follow-up period of 6.9 years.56 For glucose, there is a graded increase in CVD mortality with a progressive increase in glycemia. A follow-up evaluation of three European cohorts (>17,000 men) over 20 years showed that nondiabetic men with higher blood glucose had a significantly higher risk of death from cardiovascular disease and CAD.61 Therefore, asymptomatic glucose intolerance should no longer be considered a benign metabolic condition, and “dysglycemia” should be taken seriously not only as a prediabetic warning sign, but also as a CHD risk factor.62,63 This observation further highlights the importance of regular physical activity and exercise as effective interventions for maintaining insulin sensitivity, and thereby contributing to the maintenance of proper plasma glucose homeostasis.64-67 Waist circumference is correlated positively with abdominal fat content and may offer the clinician the most practical anthropometric measurement for assessing a patient's abdominal fat content.68 Waist measurement could therefore further refine the screening of the obese individual “at risk.” Furthermore, it has been suggested that fasting hypertriglyceridemia could substantially increase the likelihood of identifying the features of the metabolic syndrome often found among patients with an elevated waistline. For instance, it was recently reported that men with a waist circumference exceeding 90 cm and triglycerides exceeding 2.0 mmol/L had more than an 80% chance of being characterized by the features of the insulin resistance syndrome predictive of a substantially increased CHD risk.37,69 However, because there is evidence that various populations and ethnic groups may differ in the level of risk associated with a particular waist circumference, it is not currently advisable to use the aforementioned thresholds as universally acceptable. For instance, women have a greater relative risk of cardiovascular disease at lower waist circumferences than men. Also, it is likely that cardiovascular complications develop in the Asian population at much lower waist values. Thus, the development of gender- and population-specific cutoffs clearly is warranted. OBESITY AND THE ATHEROSCLEROTIC PROCESS Atherosclerosis in human arteries develops over decades from an asymptomatic phase to manifest disease. The process begins in childhood because deposits of cholesterol and its esters in the intima of large muscular arteries can be found at an early stage of life.70,71 The initial lesion of atherosclerosis leads to the development of fatty streaks, which begin to appear in the coronary arteries 5 to 10 years later than in the aorta.70 An important early event in the development of atherosclerosis is endothelial cell dysfunction and inflammation of the vessel wall. Notably, more than 40 years ago, it was suggested that atherosclerosis results at least in part from a pediatric nutrition problem.72 As individuals age, fibrous plaques develop and progress to fragile complicated lesions, which may rupture, releasing prothrombotic material and leading possibly to acute coronary events.29,30 In adults, obesity often is associated with advanced atherosclerosis. Indeed, postmortem examination of arteries from individuals 15 to 34 years old who died of accidental injuries, homicides, or suicides has showed that the extent of fatty streaks and advanced lesions (fibrous plaques and plaques with calcification or ulceration) in the right coronary artery and the abdominal aorta were associated with obesity and the size of the abdominal panniculus.73-76 Findings have associated obesity in young men, as crudely defined by the BMI, with both fatty streaks and raised lesions in the right coronary artery and with microscopic atherosclerosis and stenosis in the left anterior descending artery. Black subjects had more extensive fatty streaks than white subjects in all arterial segments examined, and men had more extensive raised lesions in the right coronary artery than women.77 Importantly, when BMI and abdominal panniculus thickness were considered simultaneously in men, a BMI of 30 kg/m2 or more was associated with raised lesions in the right coronary artery only among individuals with a large panniculus thickness ≥ 17 mm reinforcing the concept that central fat distribution is more important than total fat as a risk factor for atherosclerosis.77 Moreover the association between adiposity and right coronary artery lesions after adjustment for other risk factors, namely non-HDL and HDL cholesterol concentrations, hypertension, smoking, and glycohemoglobin, remained statistically significant because these risk factors accounted for only 15% of the variation observed in the level of atherosclerosis measured at this young age.78 Of note, however, is the fact that the raised lesions observed in the coronary arteries of young women lagged behind those in young men by about 10 to 20 years, independently of the risk factor status.78,79 This phenomenon may help to explain why postmenopausal women presented clinically significant atherosclerosis 10 years later than men. It is a relevant fact that postmenopausal women tend to deposit additional fat centrally instead of peripherally.79-81 Therefore, the data from the Pathobiological Determinants of Atherosclerosis in Youth study provide evidence that obesity in adolescents and young adults accelerates the progression of atherosclerosis decades before the appearance of clinical manifestations. For this reason, prospective studies that have reported follow-up data of more than two decades, such as the Framingham Heart Study and the Manitoba Study, have documented the fact that obesity is an independent predictor of clinical CVD.2,82,83 WEIGHT MANAGEMENT AND THE gain and obesity are associated with deleterious adaptations on the cardiovascular (Figure Although weight loss may not a to all to the it an effective to the numerous and metabolic abnormalities observed in high-risk obese are with the fact that weight is to and even more to to this is the fact that the of regular physical has been associated with the prevention of and with mortality in obese individuals and those with type 2 data from the that although of overweight to weight reported that used physical activity as a for only 20% reported being at the Because of the increased metabolic by excess body at given level of the cardiac is greater for obese subjects. It has been demonstrated that for most obese patients should be considered an exercise of to high The of a weight loss and management program are at least to further weight and weight loss can be to such reduced body weight physical activity is a for weight maintenance because it to increased thereby a generally which eventually leads to weight However, the clinician should not limit or to weight loss as a because regular exercise could even the metabolic risk profile of obese subjects the fact that these subjects be as or at the of the exercise should have BMI and levels of abdominal fat with of weight established to health outcomes risk of a first or recurrent CVD In this regard, it is suggested that the in plasma lipid profile observed with the use of exercise in patients with type 2 diabetes is largely by the loss of body Therefore, an a in and increased physical activity is the most management for weight loss and weight However, individuals often the exercise to because from at the by health Indeed, it should be in mind that and heart is higher in obese individuals than in those with normal follow-up results for patients undergoing a to weight for most of these subjects in the of These negative results the importance of physical activity or exercise into the lifestyle of and obese An important is there is a to on exercise to metabolic and the risk of CAD in obese In this regard, it was reported recently that the of exercise to have a greater than of exercise on plasma in but overweight weight loss it also is important to patients about the results to be expected from the exercise weight should not be the but rather some weight which could lead to in the risk factor the that even weight loss is obese individuals showing a level of are at less risk for cardiovascular mortality than but The clinician should therefore on of the metabolic profile rather than on weight loss A of adaptations and in cardiac and as adipose tissue in excess even in the of a less lifestyle are observed different populations, and this phenomenon has to the remarkable increase in the prevalence of individuals by the metabolic syndrome from the development of a high-risk obesity abdominal obesity. are likely to the in morbidity and mortality from CVD over the past two It also to to more on lifestyle Obesity may atherosclerosis through its on risk factors for CAD such as dyslipidemia, hypertension, glucose inflammatory and the state as as features of the metabolic syndrome. Although no prospective studies have demonstrated that weight loss there is evidence that weight loss among overweight and obese individuals reduces the of loss may the progression of atherosclerosis or the risk of acute coronary syndrome events by endothelial blood pressure, levels of and proinflammatory such as tumor necrosis and C-reactive protein; and levels of molecules such as and in a cardiac rehabilitation the features of the metabolic syndrome should be Indeed, after a or coronary artery it was shown that abnormal glucose tolerance is associated with progression of atherosclerosis in coronary Thus, after the of acute should abdominal obesity as a potentially critical cause of elevated risk in high-risk CAD should be set between the clinician and the The weight loss should be no more than to 1 per This concept is critical because it has been shown that than of obese adults have reported being to weight the of healthcare a waist circumference measurement important on a patient's health but it is important to that the between the waist circumference and visceral fat is by and Therefore, the waist circumference cutoffs are likely to differ on age, ethnicity, and The a waist circumference may be to health risk in a obesity is highly prevalent in cardiac rehabilitation and a waist circumference measurement should be to better the risk profile and to the of the lifestyle program which should a a of healthcare is by from and The Heart and is by from the for and the