INTRODUCTION — Obesity is an expanding public health problem worldwide, creating a global health epidemic. According to a 2016 World Health Organization (WHO) report, obesity has nearly tripled since 1980 with 1.9 billion adults worldwide who are considered overweight, including 650 million who were considered obese. Obesity has long been associated with an increased risk for cardiovascular diseases (CVD). Given the impact of obesity on various aspects of health, efforts at preventing obesity are urgently needed.

The evidence supporting obesity as an independent risk factor, possible mechanisms of action, and a brief discussion of the benefit of weight reduction will be reviewed in this topic. The etiology of obesity, other health hazards associated with obesity, and therapy for obesity are discussed separately.

●(See "Obesity in adults: Prevalence, screening, and evaluation".)

●(See "Obesity in adults: Etiologies and risk factors".)

●(See "Overweight and obesity in adults: Health consequences".)

●(See "Obesity in adults: Overview of management".)

●(See "Obesity in adults: Role of physical activity and exercise".)

●(See "Obesity in adults: Dietary therapy".)

●(See "Obesity in adults: Drug therapy".)

DEFINITION OF OBESITY — Obesity can be defined using a number of different parameters, including:

●Body mass index (BMI)

●Measurements of central obesity (including waist circumference and waist-to-hip ratio)

●Body composition measurements

BMI — BMI is the most practical way to evaluate the degree of obesity, although it is not a measure of body composition. Nonetheless, BMI correlates with CVD and all-cause mortality [1]. BMI is calculated from the height and weight as follows:

 BMI = body weight (in kg) / square of stature (height, in meters)

The most widely accepted BMI classifications of obesity are those from the WHO [2]:

●Underweight – BMI of <18.5 kg/m²

●Normal weight – BMI of 18.5 to 24.9 kg/m²

●Overweight – BMI of 25.0 to 29.9 kg/m²

●Grade 1 obesity – BMI of 30.0 to 34.9 kg/m²

●Grade 2 obesity – BMI of 35.0 to 39.9 kg/m²

●Grade 3 or severe obesity – BMI ≥40.0 kg/m²

Measurements of central obesity — Waist circumference and waist-to-hip ratio are surrogate estimations of visceral adiposity, which is linked to insulin resistance, dyslipidemia, and increased CVD risk [3]. These measures have been associated with CVD outcomes and mortality, and they been have been shown to inform risk assessment when used in combination with BMI categories [4], as they can be better indicators of risk in some populations [4]. Central obesity is defined as follows [5]:

●Waist circumference: men >102 cm (40 in); women >88cm (35 in)

●Waist-to-hip ratio: men ≥0.90; women ≥0.85

Body composition measurements — BMI has clear limitations to discriminate between fat-free mass, a protective factor, and fat mass, a factor associated with adverse outcomes. There seems to be a role for body composition assessment in obesity diagnosis [6], however implementation in clinical practice is limited. The American Association of Clinical Endocrinologists (AACE) recommends the use of body fat thresholds of >25 percent in men and >35 percent in women to diagnose obesity [7].

EPIDEMIOLOGY — In the United States and many countries worldwide, the prevalence of obesity trends has continued to rise since the 1980s. Among those 20 years of age or older studied from the 2007-2008 to 2015-2016 National Health and Nutrition Examination Surveys (NHANES), the following trends have been seen [8]:

●Obesity has increased from 33.7 percent to 39.6 percent of the population. In men obesity increased from 32.2 percent to 37.9 percent, while in women obesity increased from 35.4 percent to 41.1 percent.

●Severe obesity has increased from 5.7 percent to 7.7 percent.

Data from the 2015-2016 NHANES show that the increasing prevalence of obesity has affected both genders and all age groups [9]:

●Ages 20 to 39 years – 34.8 percent of men and 36.5 percent of women are obese.

●Ages 40 to 59 years – 40.8 percent of men and 44.7 percent of women are obese.

●Ages 60 years and older – 38.5 percent of men and 43.1 percent of women are obese.

The prevalence of obesity among children in the United States has also been on the rise in most age groups. Among those younger than 20 years of age studied from the 2007-2008 to 2015-2016 National Health and Nutrition Examination Surveys (NHANES), the following trends have been seen [8]:

●Ages 2 to 5 years – Obesity increased from 10.1 percent to 13.9 percent.

●Ages 6 to 11 years – Obesity decreased slightly from 19.6 percent to 18.4 percent.

●Ages 12 to 19 years – Obesity increased from 18.1 percent to 20.6 percent.

This high prevalence of obesity is observed in many countries. The 2013 Global Burden of Disease Study reported the following trends from 1980 to 2013 [10]:

●In adults, the prevalence of overweight and obese patients combined increased from 28.8 percent to 36.9 percent in men and 29.8 percent to 38.0 percent in women.

●In developed countries, more men than women were overweight and obese, whereas in developing countries, the combination of being overweight or obese was more prevalent in women than in men.

●In children and adolescents – The prevalence of overweight and obese patients combined increased in developed countries from 16.9 percent to 23.8 percent in boys and 16.2 percent to 22.6 percent in girls.

●In children and adolescents – The prevalence of overweight and obese patients combined increased in developing countries from 8.1 percent to 12.9 percent in boys and 8.4 percent to 13.4 percent in girls.

●In both developed and developing countries, sex differences in overweight and obesity trends are small.

●For all ages, prevalence was higher in developed countries than in developing countries.

MECHANISM OF RISK — The demonstration that a physical characteristic, biochemical finding, or lifestyle habit is associated with an increased risk of CVD does not by itself establish a causal relationship. A risk factor may be a primary causal agent (ie, low-density lipoprotein [LDL] cholesterol), or a facilitating causal agent (ie, hypertension, diabetes, and cigarette smoking). Obesity should be viewed in the latter category. Thus, it probably interacts with other risk factors to varying degrees in each individual.

There are a number of physiologic and metabolic changes associated with obesity that may contribute to an increased risk of CVD (see "Overweight and obesity in adults: Health consequences"):

●Insulin resistance and hyperinsulinemia — Central obesity is associated with insulin resistance and an array of metabolic and hemodynamic disorders, including hyperinsulinemia, atherogenic blood lipid changes, hypertension, and type 2 diabetes. This constellation of findings has been called the metabolic syndrome (or insulin resistance syndrome or syndrome X). Patients who have metabolic syndrome have a threefold increased risk for developing CHD or stroke [11]. (See "Metabolic syndrome (insulin resistance syndrome or syndrome X)" and "Insulin resistance: Definition and clinical spectrum".)

●Type 2 diabetes mellitus — Type 2 diabetes mellitus is strongly associated with obesity in all ethnic groups. More than 80 percent of cases of type 2 diabetes can be attributed to obesity, which may also account for many diabetes-related deaths. (See "Overweight and obesity in adults: Health consequences", section on 'Diabetes mellitus' and "Prevalence of and risk factors for coronary heart disease in patients with diabetes mellitus" and "Glycemic control and vascular complications in type 2 diabetes mellitus".)

●Lipid abnormalities, including lower high-density lipoprotein (HDL) level, higher triglyceride level, smaller LDL particles, and increased apolipoprotein B level — Obesity is associated with several deleterious changes in lipid metabolism, including high serum concentrations of total cholesterol, LDL cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, triglycerides, and a reduction in serum HDL cholesterol of approximately 5 percent [12,13]. The last effect may be most important since a low serum HDL cholesterol concentration carries a greater relative risk of CHD than hypertriglyceridemia. (See "Lipoprotein classification, metabolism, and role in atherosclerosis".)

●Systolic and diastolic hypertension — Blood pressure is often increased in obese subjects [14]. In the Swedish Obesity Study, for example, hypertension was present at baseline in approximately one-half of subjects with obesity. In a report from the Nurses' Health Study, the BMI at age 18 years and at midlife was positively associated with the occurrence of hypertension [15]. (See "Cardiovascular risks of hypertension".)

●LVH — Obesity is associated with volume overload resulting in a high end-diastolic volume and increased filling pressure. This, coupled with hypertension, can lead to LVH [16], which is important clinically because it is associated with an enhanced incidence of HF, ventricular arrhythmias, death following MI, and SCD.

●Obstructive sleep apnea — Obesity is associated with obstructive sleep apnea (OSA), which is related to excess mortality, hypertension, left and right ventricular dysfunction, inflammation, and arrhythmias [17]. The relationship between obesity and OSA is complex [18]. While obesity is the major cause of OSA, and treatment of obesity mitigates OSA severity, evidence also suggests that unmanaged OSA can further propagate weight gain and metabolic abnormalities, highlighting the importance of weight loss as the cornerstone of treatment for both conditions [18,19]. (See "Obstructive sleep apnea and cardiovascular disease in adults".)

●Increased systemic inflammation – Obesity is independently associated with increases in inflammatory markers that mediate the association with CVD risk [20]. C-reactive protein (CRP) is both the most extensively studied marker of inflammation in obesity and the most widely used in clinical practice. Epidemiologic studies also suggest a direct link between interleukin (IL)-6 and tumor necrosis factor-alpha and the increased CVD risk in obesity. (see "Overview of established risk factors for cardiovascular disease")

●Sympathetic nervous system activation – Sympathetic nervous system activation has been observed in obesity, and the consequences include hypertension and increased afterload, probably attributable to activation of the sympathetic outflow to the kidneys and insulin resistance [20,21].

●Endothelial dysfunction – Endothelial dysfunction is the inability of the endothelium to optimally regulate vascular tone, hemostasis, and vascular inflammation. Endothelial dysfunction in obesity is mainly determined by systemic inflammation, nitric oxide (NO)-bioavailability, oxidized LDL and insulin resistance (see "Coronary endothelial dysfunction: Clinical aspects").

ASSOCIATION WITH OBESITY WITH VARIOUS CONDITIONS — Despite uncertainties about the relationship between obesity and CVD, the current guidelines identify obesity as an independent risk factor [22]. This action should heighten clinician awareness about the importance of obesity and stimulate a more vigorous approach to prevention and treatment that takes fat distribution and risk factor prevalence into account. (See "Obesity in adults: Overview of management".)

Mortality — Obesity has been associated with increased total mortality in a variety of cohorts [23-27].

●In a prospective cohort study of over one million adults without a history of coronary heart disease (CHD) who were followed for 14 years, obesity was strongly associated with an increased risk of all-cause mortality and CVD death [27]. All-cause mortality was lowest in adults with a BMI between 23.5 and 24.9 kg/m² in men and 22 and 23.4 kg/m² in women.

●In the Nurses' Health Study, which evaluated the relationship between BMI and total cause specific mortality in 115,195 women from the United States, there was a significant trend for increasing risk of death with increasing BMI [23]. Compared with women with a BMI <19.0 kg/m², the relative risk of death was: 1.2 for a BMI of 19.0 to 24.9 kg/m²; 1.3 for a BMI of 25.0 to 26.9 kg/m²; 1.6 for a BMI of 27 to 28.9 kg/m²; and 2.1 to 2.2 for a BMI >29.0 kg/m². The risk of death was increased at BMI levels well below those considered to indicate obesity, with a striking increase in risk for truly obese women.

●A 2013 systematic review and meta-analysis of 97 studies compared all-cause mortality for overweight and obese persons to normal weight persons using BMI [25]. The findings suggested increased mortality rates with obesity, although only statistically significant with grade 2-3 obesity. Additionally they observed lower mortality for overweight individuals. (See 'Definition of obesity' above.)

●In contrast, in a meta-analysis of 239 prospective studies across four continents, which examined the association of BMI categories with all-cause mortality, there was a linear relationship between greater BMI and mortality. When restricting the analysis to patients who had never smoked and did not have baseline CVD on the first five years of follow-up, a BMI of 25 kg/m² or more was associated with greater all-cause mortality (hazard ratio 1.31 per 5 kg/m² units higher BMI) [26].

Obesity and CHD — There is strong, consistent epidemiologic evidence for an association between obesity and CHD, with significant risk associated with obesity beginning as early as childhood [28-31]. (See "Obesity in adults: Overview of management", section on 'Mortality'.)

●As an example, the Munster Heart Study (PROCAM) followed 16,288 men and 7325 women for up to seven years [29]. There was a graded positive relationship between BMI and other CHD risk factors including age, total serum cholesterol, low-density lipoprotein (LDL) cholesterol, and systolic and diastolic blood pressure in addition to markers of inflammation and thrombosis. The increase of CHD death associated with BMI was completely accounted for and mediated by these risk factors.

●In a meta-analysis of studies assessing the impact of body weight on CHD, there was a 29 percent increase in CHD for each five-unit increase in BMI. The risk of CHD in obese and overweight persons is compounded by the frequent coexistence of other CHD risk factors such as hypertension, dyslipidemia, and diabetes. How much of the risk is due to obesity alone has been uncertain [30].

Abdominal obesity — At any given level of BMI, the risk of the development of CVD in both men and women is increased with central obesity [32]. (See "Obesity in adults: Prevalence, screening, and evaluation", section on 'Waist circumference'.)

●The relationship between abdominal obesity and CVD mortality was evaluated in a cohort of 44,636 women in the Nurses' Health Study [33]. The relative risk increased significantly from the lowest to the highest waist circumference quintiles (1.00, 1.04, 1.04, 1.28, and 1.99 respectively) after adjustment for BMI and other confounders during 16 years of follow-up. This relationship persisted even among normal weight women (BMI 18.5 to <25 kg/m²).

●In a study of 27,098 patients in 52 countries which compared BMI and waist-to-hip ratio and associated risk of MI. BMI showed a modest association with MI (odds ratio [OR] 1.44, 95% CI 1.32-1.57), which was substantially reduced after adjustment for waist-to-hip ratio (OR 1.12, 95% CI 1.03-1.22) For waist-to-hip ratio, the ORs for every successive quintile were significantly greater than that of the previous one (fourth quintile OR 1.90, 95% CI 1.74-2.07; and fifth quintile OR 2.52, 95% CI 2.31-2.74) [34].

●The prognostic effect of combining BMI and measures of central obesity with total CVD mortality was studied in the NHANES III. For example, a man with a normal BMI and central obesity had nearly twofold greater total mortality risk than a man with similar BMI but no central obesity, and this patient had twice the mortality risk of participants who were overweight or obese according to BMI only. Similar findings were noted in women [4].

Heart failure — In addition to the association with CHD, there is an important association between obesity and heart failure (HF), especially HF with preserved ejection fraction [20,35-37] (figure 1). In an analysis from the Framingham Heart Study, in which almost 6000 individuals without a history of HF (mean age 55 years) were followed for a mean of 14 years, the risk of HF was increased approximately twofold in subjects with obesity compared with non-obese subjects [38]. After adjusting for established risk factors (ie, hypertension, CHD, diabetes, left ventricular hypertrophy [LVH]), the risk for HF increased 5 percent in men and 7 percent in women for each increment of 1 kg/m² in BMI. (See "Epidemiology and causes of heart failure" and "Overweight and obesity in adults: Health consequences".)

Atrial fibrillation — Atrial fibrillation (AF) is the most common arrhythmia in adults, with prevalence rates that are expected to rise by threefold in the next few decades [39]. Several obesity-related factors contribute to this epidemic of AF; obesity leads to left atrial remodeling via various mechanisms, and it is associated with a marked increase in the risk of developing AF. The ARIC (Atherosclerosis Risk In Communities) study estimated that one in five cases of AF can be attributed to obesity [40]. Conversely, as observed in other CVDs, it has been suggested that while obesity increases the risk for incident AF, overweight and obese patients with AF seem to have a better prognosis, including a lower CVD and all-cause mortality, compared to lean AF patients, suggesting an obesity paradox [39].

Sudden cardiac death — Whereas the most common reported cause of death in obese patients is HF, there is growing evidence of an increased risk of sudden cardiac death (SCD) in people with obesity [41]. Individuals with an elevated BMI or central obesity are more likely to have prolonged QT intervals, and this has been proposed as a potential mechanism for SCD in people with obesity, in addition to the increased risk for CHD [42].

METABOLICALLY "HEALTHY" OBESITY — A phenotype called metabolically "healthy" obesity (MHO) refers to obese individuals who have relatively normal levels of plasma lipids, glucose, and blood pressure. While historically it has been unclear as to whether these individuals are at an increased risk of CVD, especially CHD [43], evidence suggests that these individuals tend to develop metabolic dysregulation and likely have increased cardiovascular risk in the long-term [44,45].

●In a 2013 meta-analysis of eight studies (61,386 adults with nearly 4000 adverse cardiac events over more than 10 years of follow-up), obese adults, including those without significant metabolic derangements, were at increased risk for adverse events compared with metabolically healthy normal weight adults [46]. Obese adults who were metabolically healthy (defined as the absence of components of the metabolic syndrome) had a 24 percent increased risk for increased events compared with normal weight, metabolically healthy adults.

●Data from the Copenhagen General Population Study suggest that being overweight or obese increases the risk for myocardial infarction (MI) and ischemic heart disease, irrespective of the presence or absence of criteria for the metabolic syndrome [47]. In this study of 71,527 adults (median follow-up 3.6 years), both overweight and obese adults without metabolic syndrome had an increased risk for MI compared with normal weight adults without metabolic syndrome (adjusted hazard ratio [HR] 1.26; 95% CI 1.0-1.61 in overweight adults and HR 1.88; 95% CI 1.3-2.6 in obese adults).

●An analysis of the contemporary Multi-Ethic Study of Atherosclerosis followed 6809 subjects for 12.2 years, and reported that even though those with MHO did not have an increased risk of incident CVD, nearly half of these individuals developed metabolic abnormalities and subsequently developed increased CVD risk [44]. Similar findings were observed in the Whitehall II cohort study of British adults, where over 20 years of follow-up, a high number of those with MHO eventually developed "metabolic un-healthiness" [48].

●A large study of electronic health records (1995 to 2015) in The Health Improvement Network (THIN) that included 3.5 million adults free of established CVD at baseline, with and without metabolic abnormalities. During follow-up of 5.4 years, obese individuals with no metabolic abnormalities had a higher risk of CHD (multivariate-adjusted HR 1.49; 95% CI 1.45-1.54), cerebrovascular disease (HR 1.07; 95% CI 1.04-1.11), and HF (HR 1.96; 95% CI 1.86 -2.06) compared with normal weight individuals with no metabolic abnormalities. Concluding that Risk of CHD, cerebrovascular disease, and HF in normal weight, overweight, and obese individuals increased with a growing number of metabolic abnormalities [49].

OBESITY PARADOX — Although obesity increases the risk for a number of established CVD risk factors, overweight or obese subjects with established CHD may have better prognosis compared to their leaner counterparts. This phenomenon has been referred to as the "obesity paradox." The obesity paradox is seen in many forms of CVD and also other diseases, such as end-stage kidney disease, human immunodeficiency virus and various pulmonary diseases [50]. Although the obesity paradox has been observed for most CVD, it most likely applies to the overweight patient and those with Grade I obesity, and less for Grade II or greater obesity. The possible explanations for the obesity paradox include reverse causality (thin patients are sicker), the inability of BMI to distinguish fat tissue from muscle mass and even the possibility that adipose tissue may provide protection during acute severe illnesses where caloric intake is severely disrupted. The evidence for an obesity paradox is mixed for individuals with BMI between 22 and 24.9, but the evidence showing increased mortality in individuals with lower BMI values is indisputable. (See "Obesity in adults: Overview of management", section on 'Mortality'.)

●In the AF Follow-up Investigation of Rhythm Management (AFFIRM) trial, patients with higher BMI had lower all-cause mortality than normal-weight patients over a three-year follow-up period (adjusted HR 0.77; 95% CI 0.62-0.95) [51].

●Among 2625 participants with new-onset diabetes mellitus in five longitudinal cohort studies, all-cause mortality rates were higher among normal-weight people than overweight/obese participants (adjusted HR 2.08, 95% CI 1.52-2.85) [52].

●Using data from the Nurses' Health Study and Health Professional Follow-up Study to examine the relationship between BMI and all-cause mortality among men and women with diabetes, there was no evidence of an obesity paradox in diabetic men and women [53]. Participants with a BMI between 22.5 and 24.9 had the lowest mortality.

BENEFITS OF WEIGHT LOSS — Weight loss improves or prevents many of the obesity-related risk factors for CVD [54]. Benefits include:

●Decreased blood pressure in hypertensive patients [55,56]

●Decreased incidence of diabetes mellitus [57,58]

●Improved lipid profile [59]

●Decreased insulin resistance [58]

●Reduced C-reactive protein concentration [55]

●Improved endothelial function [60]

Achieving and maintaining weight loss is made difficult by the reduction in energy expenditure that is induced by weight loss. In addition, recidivism (regaining of lost weight) is a common problem. Of those subjects who lose weight during any treatment program, most do not maintain the weight loss. Importantly, physical activity may be more important than achieving a normal BMI in patients with CHD. Changes in physical activity correlate with better survival whereas changes in BMI, including weight loss, do not [61,62]. (See "Obesity in adults: Overview of management", section on 'Importance of weight loss' and "Obesity in adults: Role of physical activity and exercise".)

Health care providers should urge patients to lose weight, especially if accomplished with increases in physical activity and improvements in cardiorespiratory fitness (algorithm 1). Prevention of obesity beginning in early life may be perhaps the best strategy to reduce the burden of CVD in the population. In obese older adults, recommendations for weight loss are controversial. Moderate weight loss may have beneficial effects on comorbidities, functional performances, and quality of life provided that regular physical activity can be associated [63].

Drug therapy may be a helpful component of treatment for overweight subjects. However, among patients with CVD, certain drugs may be contraindicated. Anti-obesity drugs have been used as an adjunct to diet and exercise for obese subjects with a BMI greater than 30 kg/m². The role of drug therapy has been questioned, however, because of concerns about long term effectiveness, the potential for abuse, and side effects. (See "Obesity in adults: Drug therapy".)

Bariatric procedures are an option for patients at high risk of complications from obesity (algorithm 1) and have shown to be relatively safe and effective [64]. Major examples on the benefit of significant weight loss can be observed in patients that undergo bariatric procedures (gastric bypass or banding) that reduce CVD risk factors, including metabolic components (blood pressure, diabetes incidence, improve lipid profiles) and clinical outcomes (improvements in quality of life [65], non-fatal CVD outcomes [65], and lower mortality [66]). These benefits do not appear to occur with liposuction [67], suggesting that the negative energy balance associated with decreased nutritional intake may be necessary for achieving the metabolic benefits of weight loss. (See "Bariatric surgery for management of obesity: Indications and preoperative preparation".)

The ACC/AHA guidelines for the management of patients with stable ischemic heart disease made the following recommendations for weight management [68]:

●Regular assessment of BMI and recommend assessing waist circumference at all BMI levels.

●Counseling on weight management at each patient visit, with a goal of a BMI between 18.5 and 24.9 kg/m².

●The initial goal of weight loss should be approximately 10 percent from baseline.

●Lifestyle changes and consideration of treatment strategies for metabolic syndrome. (See "Metabolic syndrome (insulin resistance syndrome or syndrome X)", section on 'Therapy'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Health risks of obesity (The Basics)" and "Patient education: Weight loss treatments (The Basics)")

●Beyond the Basics topics (see "Patient education: Losing weight (Beyond the Basics)")

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary prevention of cardiovascular disease" and "Society guideline links: Secondary prevention of cardiovascular disease" and "Society guideline links: Lifestyle management and cardiac rehabilitation" and "Society guideline links: Obesity in adults".)

SUMMARY AND RECOMMENDATIONS

●Obesity is an expanding public health problem worldwide, with a near tripling of the prevalence of worldwide obesity since 1980. Given the impact of obesity on various aspects of health, efforts at preventing obesity are urgently needed. (See 'Introduction' above.)

●Body mass index (BMI) is the most practical way to evaluate the degree of obesity, although it is not a measure of body composition. Nonetheless, BMI correlates with cardiovascular disease (CVD) and all-cause mortality. BMI is equal to body weight (in kilograms) divided by square of stature (height, in meters). Overweight is defined as a BMI between 25.0 and 29.9 kg/m² and obesity as a BMI greater than 30 kg/m². (See 'BMI' above.)

●There are a number of physiologic and metabolic changes associated with obesity that may contribute to an increased risk of CVD, including insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, lipid abnormalities, hypertension, obstructive sleep apnea, systemic inflammation, sympathetic nervous system activation, and endothelial dysfunction. (See 'Mechanism of risk' above.)

●At any given level of BMI, the risk of the development of CVD in both men and women is increased by greater amounts of abdominal fat, resulting in an increased waist circumference or waist to hip ratio (See 'Measurements of central obesity' above.)

●Obesity is an independent risk factor for the development of CVD, although the exact extent of the relationship has been variable in different populations of patients. Obesity is also associated with a greater risk of overall and CVD mortality as well as the development of HF. (See 'Association with obesity with various conditions' above.)

●A phenotype called metabolically "healthy" obesity (MHO) refers to obese individuals who have relatively normal levels of plasma lipids, glucose, and blood pressure. While historically it has been unclear as to whether these individuals are at an increased risk of CVD, especially CHD, evidence suggests that these individuals tend to develop metabolic dysregulation and likely have increased cardiovascular risk in the long-term. (See 'Metabolically "healthy" obesity' above.)

●Health care providers need to encourage patients with known CVD or CVD risk factors (ie, hypertension, dyslipidemia, type 2 diabetes mellitus) to lose weight, especially with physical activity and exercise training that increases levels of cardiorespiratory fitness. Dietary and lifestyle modifications should be the initial approach in the majority of patients, with pharmacologic and surgical therapy considered in selected patients. (See 'Benefits of weight loss' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Melvyn Rubenfire, MD, Elizabeth Jackson, MD, MPH, and Geoffrey Barnes, MD, MSc, who contributed to an earlier version of this topic review.