Obesity: Medical and Surgical Management

Traditional Definition of Obesity

Obesity increases risk of developing numerous health outcomes, including cardiovascular events ( Fig. 30.1 ). Clinical practice commonly uses body mass index (BMI, expressed in kg/m ² ) to estimate adiposity. Many population-based studies, including a recent international study pooling data of about 4 million individuals from 189 studies who were followed for an average of 13 years, have shown that a BMI value above approximately 25 kg/m ² associates with a progressive increase in mortality rate and risk of chronic conditions. A BMI of 25 kg/m ² or higher defines overweight, BMI of 30 kg/m ² or higher defines obesity , and BMI of 40 kg/m ² or higher, or 35 kg/m ² or higher with comorbidities, defines severe obesity . The prevalence of obesity has increased worldwide, particularly since the early 1980s, with little evidence of plateauing ( eFig. 30.1 ). ^, The prevalence of severe obesity has reached epidemic proportions in the United States and elsewhere. ^{, ,}

The Puzzling Relationship of Excess Body Weight and Fat with Cardiovascular Disease

Although excess body weight or obesity associates with an increased risk of many health complications (see Fig. 30.1 ), equally overweight or obese patients display a remarkable heterogeneity in CVD risk ( Fig. 30.2 ). ^{, ,} Thus, although an elevated BMI increases the risk of CVD or of other health complications, not every overweight/obese patient develops risk factors or health issues. Some investigators use the term “metabolically healthy” or “fit fat” obesity to refer to such individuals. ^{, ,} The existence of such metabolically healthy obese individuals has engendered debate. Indeed, there is no healthy pattern of increased weight. ^, Nevertheless, reasons for such major individual differences in the cardiometabolic risk profile of equally obese patients had remained unclear until imaging studies (computed tomography [CT] and then magnetic resonance imaging [MRI]) revealed marked individual differences in the way people store adipose tissue in the visceral depot. ^{, ,} For any given level of total body fat, individuals characterized by a low accumulation of abdominal visceral adipose tissue generally have a lower CVD risk profile than individuals closely matched for BMI or for total body fat but with high levels of visceral adipose tissue. Those with excessive visceral fat display a constellation of metabolic abnormalities, including insulin resistance, glucose intolerance leading to type 2 diabetes, atherogenic dyslipidemia (including increased triglyceride levels, increased concentrations of non-high-density lipoprotein [HDL] cholesterol and apolipoprotein B, low HDL cholesterol levels, small dense low-density lipoprotein [LDL] and HDL particles), elevated blood pressure (BP), subtle chronic inflammation, and a prothrombotic profile (see Fig. 30.2 ). ^, This risk cluster characterizes the so-called metabolic syndrome. ^,

In clinical practice, assessing CVD risk specifically related to obesity or excess adiposity has remained a challenge. After control for intermediate CVD risk factors (BP, lipids, diabetes), anthropometric adiposity indices such as BMI or waist circumference do not relate independently to CVD mortality. However, very strong associations between adiposity indices and intermediate CVD risk factors are observed, suggesting that increased adiposity changes CVD risk ( eFig. 30.2 ). Thus, the clinician must decide whether to reduce CVD risk by lowering BP, lipids (LDL cholesterol), and blood glucose with pharmacologic agents or to target weight loss. Whereas randomized trials have shown the clinical benefits of targeting BP, lipids, and glucose control (within certain limits), no weight loss drug specifically targeting obesity has proven unequivocally able to reduce cardiovascular events and mortality, with the exception of new diabetes drugs, which are not neutral in terms of body weight (see also Chapter 31 ). A large well-conducted diet and weight loss trial in obese patients with type 2 diabetes (Look AHEAD) showed no reduction in CVD events as a result of an intensive lifestyle intervention that yielded weight loss , despite beneficial effects on some CVD risk factors and quality of life. Various explanations may account for this result.

Risk Assessment in Overweight/Obese Patients: Waistline as a Vital Sign

Because excess visceral adiposity exacerbates CVD risk in overweight and obese patients, a panel of international experts has recommended measurement of the patient’s waist circumference in addition to BMI. This variable should be assessed while the patient is standing, placing the tape just above the iliac crest. If a given patient has a large waistline for a given BMI, with altered risk factors, the CVD risk factor profile likely reflects excess abdominal visceral fat. ^{, , , ,} Simple clinical alterations (e.g., high-triglyceride low-HDL cholesterol dyslipidemia, elevated BP, increased fasting blood glucose levels) confirm a dysmetabolic state. Additional tests to confirm insulin resistance include fasting insulin, 2-hour glucose tolerance, hemoglobin (Hb) A _1c level, and high-sensitivity C-reactive protein (hsCRP) concentrations. In overweight or obese patients, the presence of these abnormalities along with an elevated waist circumference suggests an excess of abdominal visceral fat. ^{, , , ,}

Because the waistline and BMI correlate strongly, waist circumference alone largely reflects total adiposity. For any given BMI value, however, waist circumference can vary considerably and reflects CVD risk ( Fig. 30.3 and eFig. 30.3 ). Thus, although clinical guidelines have proposed waist cutoff values to define abdominal obesity, interpretation of these cutoffs requires caution. For example, a waist circumference of 105 cm reflects abdominal obesity in a man with a BMI of 26 kg/m ² . However, the same waistline value would simply reflect overall obesity in another individual with a BMI of 31 kg/m ² . Further work is required to refine clinically relevant BMI-specific waist cutoff values beyond those specified in current guidelines ( Table 30.1 ). ^{, ,}

Evolving Focus from Adipose Tissue Mass to Quality and Functionality

As mentioned, the regional distribution of body fat is much more important than adipose tissue mass. ^{, , , ,} For example, excess accumulation of body fat in the lower part of the body (hips and thigh) does not associate with an increased risk of CVD or type 2 diabetes. Indeed, a large accumulation of lower body fat rather links with a reduced risk of developing these outcomes, consistent with previous findings that hip and thigh fat are associated with a favorable CVD risk profile. ^, In contrast, excess abdominal fat, particularly visceral adipose tissue, confers heightened risk as previously detailed. ^{, ,} Imaging also showed substantial individual differences in the size of these inner fat depots, particularly the amount of fat in the abdominal cavity, which includes omental fat, mesenteric fat, and retroperitoneal adipose tissue. ^{, , ,}

Marker of Ectopic Fat Deposition

The mechanisms underlying the independent association between excess visceral fat and cardiometabolic alterations remain unsettled. Three non–mutually exclusive scenarios may pertain: (1) the portal free fatty acid (FFA) hypothesis, (2) the endocrine functions of visceral adipose tissue, and (3) excess visceral adipose tissue as a marker of dysfunctional subcutaneous adipose tissue. ^{, ,}

Visceral Adipose Tissue: Marker of Dysfunctional Subcutaneous Adipose Tissue?

Excess visceral adipose tissue may also accumulate when subcutaneous adipose tissue fails to expand in an energy surplus ( Fig. 30.4 ). ^{, ,} Subcutaneous adipose tissue normally expands first by adipocyte hypertrophy, followed by proliferation of surrounding preadipocytes (hyperplasia). ^{, ,} If the hyperplastic response is adequate, subcutaneous adipose tissue will expand and act as a “sink” for excess calories ^{, ,} and will maintain autonomic balance.

Genetic forms of lipodystrophy illustrate the importance of properly functioning and expanding (when required) adipose tissue. ^, Individuals lacking subcutaneous fat develop an excess of visceral adipose tissue as well as fat accumulation in normally lean tissues. Large cohort imaging studies have revealed that viscerally obese individuals have an increased accumulation of fat in lean tissues such as the liver, heart, skeletal muscle, and kidney, a phenomenon described as “ectopic fat deposition.” ^{, , ,} Thus, excess visceral adipose tissue may be a marker or consequence of the relative inability of subcutaneous adipose tissue to act as a protective “metabolic sink” and thus favor ectopic fat deposition ( Fig. 30.5 ).

The extent to which each of these ectopic fat depots contributes to various cardiovascular outcomes is currently under investigation in several laboratories. ^{, , ,} Considerable evidence suggest that excess liver fat is also a key abnormality responsible for the several cardiometabolic complications found in viscerally obese individuals. ^, Similar data also link excess epi/pericardial fat with various clinical outcomes. On the other hand, the more favorable cardiometabolic risk profile and low levels of visceral/ectopic fat observed in premenopausal obese women with large hips and selective accumulation of lower body fat remain consistent with the protective role of lower body subcutaneous adipose tissue.