Healthcare in India

Obesity and Cardiovascular Disease: Risk factors, Paradox and Impact of Ergo-anthropometric Assessment

Obesity has reached global epidemic proportions and is associated with numerous comorbidities, including hypertension (HTN), type II diabetes mellitus, dyslipidemia, obstructive sleep apnea and sleep-disordered breathing, certain cancers, and major cardiovascular (CV) diseases. Because of its maladaptive effects on various CV risk factors and its adverse effects on CV structure and function, obesity has a major impact on CV diseases, such as heart failure (HF), coronary heart disease (CHD) , sudden cardiac death and atrial fibrillation, and is associated with reduced overall survival. Despite this adverse association, numerous studies have documented an obesity paradox in which overweight and obese people with established CV disease, including HTN, HF, CHD, and peripheral arterial disease, have a better prognosis compared with non overweight/ non obese patients. This review summarizes the adverse effects of obesity on CV disease risk factors and its role in the pathogenesis of various CV diseases, reviews the obesity paradox and potential explanations for these puzzling data, and concludes with a discussion regarding the current state of weight reduction, physical activity and fitness in the prevention and treatment of CV diseases.
Obesity has been increasing in epidemic proportion in both adults and children.1 In adults, overweight is defined as a body mass index (BMI) 25 to 29.9 kg/m2 and obesity as BMI > 30 kg/m2. Besides BMI, BMI/body fatness may differ considerably among people of different age, sex, and race, thus obesity may be defined by other methods, including waist circumference (WC), waist-hip ratio (WHR), and percent body fat assessment which at times are more justifiable.2 Recent evidence indicates that obesity is associated with more morbidity than smoking, alcoholism, and poverty and if current trends continue, obesity may soon overtake cigarette abuse as the leading cause of preventable death in the U.S. atleast,3 reversing the steady increase in life expectancy.4

There are numerous adverse effects of obesity on general, and especially, cardiovascular (CV) health

Although obesity has been implicated as one of the major risk factors for hypertension (HTN), heart failure (HF), and coronary heart disease (CHD), evidence from clinical cohorts of patients with established CV diseases indicates an obesity paradox because overweight and obese patients with HTN, HF, CHD, and peripheral arterial disease (PAD) tend to have a more favorable short and long-term prognosis


This article reviews the metabolic consequences of obesity as well as its pathological effects on blood pressure and CV structure and function contributing to its role in HTN and HF as well as to its role in increasing CHD and atrial fibrillation (AF). It also reviews the evidence for the obesity paradox in these disorders. Finally, the current evidence for the potential risks and benefits of purposeful weight loss and physical activity in terms of fitness are discussed.

Pathophysiology of Obesity

The adipocyte acts as an endocrine organ, and plays a substantial role in the pathogenesis and complications of obesity.6 Increased levels of leptin, an adipocyte-derived hormone that controls food intake and energy metabolism, may be particularly related with CV disease.7 C-reactive protein (CRP) may play a role in the development of leptin resistance, which is important because endogenous hyperleptinemia does not reduce appetite or increase energy expenditure.8  Clearly, the increase in inflammatory markers is associated with insulin resistance, obesity, and CV events.  

Obesity increases total blood volume, cardiac output, and cardiac workload. Typically, obese patients have a higher cardiac output caused by stroke volume, but a lower level of total peripheral resistance at any given level of arterial pressure,9 although, heart rate is typically mildly increased because of increased sympathetic activation.10  This is associated with increase in filling pressure and volume, thus increasing CV work developing left ventricular (LV) chamber dilation.9,10 Obese patients are more likely to be hypertensive than lean patients, and weight gain is typically associated with increase in arterial pressure.10 Independent of arterial pressure and age, obesity increases the risk of left ventricular hypertrophy (LVH), as well as other structural abnormalities, including concentric remodeling (CR) and concentric LVH.11 In addition to LV structural abnormalities, obesity also leads to left atrial (LA) enlargement, both from increased circulating blood volume as well as abnormal LV diastolic filling.9 These abnormalities not only increase the risk of HF, but LA enlargement may increase the risk of AF thereby morbidity.12 In addition, obesity has adverse effects on diastolic and systolic function.9,13
Clinical Consequences of Obesity

Obesity and Hypertension (HTN) and the Paradox

Typically, HTN leads to thickening of ventricular walls without chamber dilation, a process referred to as CR when LV mass is not increased or concentric LVH when LV mass is increased, whereas obesity is characterized as increase in chamber dilation without marked increase in wall thickness, a process that leads to eccentric LVH.3,11

Despite having a higher prevalence of HTN in obesity, recent data have shown an obesity paradox. Uretsky et al.14 investigated the effects of obesity on CV outcomes in 22,576 treated hypertensive patients with known CHD. During 2-year follow up, all-cause mortality was 30% lower in overweight and obese patients, despite less effective blood pressure control in these patients compared with the normal weight group. Previous studies also showed decreased stroke risk and total mortality among overweight patients compared with lean patients.15 In aggregate, these studies suggest that although obesity may be a powerful risk factor for HTN and LVH, obese hypertensive patients may paradoxically have a better prognosis, possibly because of having lower systemic vascular resistance and plasma renin activity compared with more lean hypertensive patients.

Obesity and Heart Failure (HF) and the Paradox

In a study of 5,881 Framingham Heart Study participants, Kenchaiah et al.17 showed that during a 14-year follow-up, for every 1 kg/m2 increment in BMI, the risk of HF increased 5% in men and 7% in women. In fact, a graded increase in the risk of HF was observed across all categories of BMI. In a study of 74 morbidly obese patients, nearly one-third had clinical evidence of HF, and the probability of HF increased dramatically with increasing duration of morbid obesity.13

Despite the known adverse effects of obesity on both systolic and particularly diastolic CV function and the epidemiologic data showing a strong link between obesity, generally defined by BMI criteria, and HF, many studies have suggested that obese HF patients had a better prognosis.18 In a recent meta-analysis of 9 observational HF studies (n ? 28,209) in which patients were followed up for an average of 2.7 years, Oreopoulos et al.19 showed that compared with individuals with normal BMI, over-weight and obese HF patients had reductions in CV (~19% and ~40%, respectively) and all-cause (~16% and ~33%, respectively) mortality. Although these investigators raised the possibility that selection bias and baseline characteristics may have affected these results, they also suggested that excess body weight may confer some protective effects on HF mortality.20 Because advanced HF is a catabolic state, obese patients with HF may have more metabolic reserve.21 Cytokines and neuroendocrine profiles of obese patients also may be protective.19  Adipose tissue produces soluble tumor necrosis factor-alpha receptors and could play a protective role in obese patients with acute or chronic HF by neutralizing the adverse biological effects of tumor necrosis factor-alpha.22Additionally, overweight and obese patients with acute and chronic HF have lower levels of circulating atrial natriuretic peptides,23 attenuated sympathetic nervous system and renin-angiotensin responses19 and may tolerate higher levels of cardioprotective medications.19 Higher circulating lipoproteins in obese patients may bind and detoxify lipopolysaccharides that play a role in stimulating the release of inflammatory cytokines, all of which may serve to protect the obese patient with HF.21 Unfortunately, these studies do not typically adjust BMI for other measures of adiposity (e.g., waist circumference and waist hip ratio).

Obesity and Coronary Heart Disease (CHD) and the Paradox

Obesity is probably an independent risk factor for atherosclerosis and CHD events.24 Additionally, excess adiposity has been strongly related to first non–ST-segment myocardial infarction (MI) occurring at a younger age.25

Nevertheless, as with HTN and HF, many studies have also reported an obesity paradox in CHD, including in patients treated with revascularization.26 In a recent systematic review of over 250,000 patients in 40 cohort studies followed up for 3.8 years, Romero-Corral et al.26 reported that overweight and obese CHD patients have a lower risk for total and CV mortality compared with underweight and normal-weight CHD patients. However, in patients with a BMI >35 kg/m2, there was an excess risk for CV mortality without any increase in total mortality. Importantly, the obesity paradox has also been shown in patients after MI and revascularization, and more recently has been shown in patients referred for exercise stress testing.27 Although the mechanism for this effect is uncertain, these studies suggest that despite the fact that obesity increases the risk for developing CHD, at least overweight and mild obesity do not seem to adversely affect prognosis in patients with established CHD.

Obesity Paradox in Other CV Populations

Galal et al.28 have recently assessed 4.4-year mortality in 2,392 patients with PAD who had undergone major vascular surgery and had high mortality risk during follow-up. This study also showed a powerful obesity paradox, with progressive reductions in mortality in normal BMI, overweight, and obese groups compared with underweight patients.

E) Obesity and Atrial Fibrillation
Prevalence of AF increases with obesity, and is expected to increase 2.5-fold by 2050.29 Although the increase in AF may be attributable to the aging of our population combined with the improved prognosis of HTN, CHD, and HF, conditions that increase the risk of AF, the epidemic of obesity, with its attendant hemodynamic effects and impact on LV and LA structure and function, may also contribute to the higher prevalence of AF.12 In a subgroup of 5 population-based studies enrolling 78,602 patients, obese patients had a nearly 50% increased risk of developing AF that escalated with increasing BMI.29 On the other hand, post-cardiac surgery studies enrolling 44,647 patients failed to show an increased risk of AF in obesity.

F) Obesity and Stroke
Numerous studies have reported an association between BMI and stroke.1 For each 1-U increase in BMI, there was an increase of 4% in the risk of ischemic stroke and 6% for hemorrhagic stroke.30 This increased risk of stroke may be attributable to a higher prevalence of HTN, a prothrombotic/proinflammatory state that accompanies excess adipose tissue accumulation, as well as increased AF.

G) Obesity and Ventricular Arrhythmias
Although progressive HF may be the most common cause of death in patients with obesity cardiomyopathy, sudden cardiac death (SCD) has been reported to be increased in apparently healthy obese patients.1 Substantial evidence supports an increased electrical irritability in obesity that may lead to more frequent and complex ventricular dysrhythmias,10 even in the absence of LV dysfunction or clinical HF. In the Framingham Heart Study,31 the annual SCD rate was nearly 40 times higher than in a matched non-obese population.10

A positive association between corrected QT (QTc) interval and BMI has been noted, and prolonged QTc has predicted increased mortality even in apparently healthy populations.32  Although a relationship between QTc and increased obesity has been noted in many studies, this is most evident in the severely obese.33  These could be related to pathological changes noted with cardiomyopathy of obesity (adipositas cordis), including myocyte hypertrophy, fibrosis, and fat and mononuclear cell infiltration.1 Also, obesity is associated with abnormalities in sympathovagal balance, leading to higher heart rate and reduced heart rate variability, known factors related with increased risk of SCD.2

H) Obesity and Sleep Apnea
Obesity is a classic cause of alveolar hypoventilation and the obstructive sleep apnea (OSA) syndrome.34 In fact, OSA may contribute to the pathogenesis of HTN and increased inflammation and CRP.35 Clearly, patients with OSA have increased risk of HTN, dysrhythmias, pulmonary HTN (present in 15% to 20% with OSA), HF, MI, stroke, and overall mortality.36

I) Obesity and Venous Disease
The combination of increased intravascular volume and high-volume lymphatic overload, as well as reduced physical activity, often lead to venous insufficiency and edema with increasing obesity.37 Additionally, obesity is associated with an increased risk for venous thromboembolism and pulmonary embolism, especially in women.38
Several previous studies have reported an obesity paradox in specific CVD (HTN, HF, CHD, and PAD) populations. The justification could be based on several mechanisms, few of which are mentioned below. Besides circulating endogenous substances, attenuated sympathetic nervous system and renin-angiotensin responses, greater coronary artery size among patients with higher BMI has been proposed as a possible mechanism for the obesity paradox .The veteran effect, suggesting that adult-onset obesity is less hazardous than obesity developing in childhood or adolescence could stand as an obesity paradox hypothesis and the healthy obesity state-a recently identified metabolically benign form of obesity as the cause of the obesity paradox. In this context, a practical alternative could be a combined assessment of Ergo-anthropometric classification which includes assessment of waist circumference and physical fitness, in addition to BMI. This assessment has advantages viz.

  1. the risk score is modified if life style is sedentary or unfit.
  2. it allows identification of sedentary-normal weight, active-overweight, active-obese, sedentary-overweight and sedentary-obese subgroups who have an increased risk.

Status of Weight Reduction, Physical Activity and Cardiorespiratory Fitness

  1. Match intake of energy (calories) to overall energy needs; limit consumption of foods with a high- caloric density and /or low nutritional quality including those with a high content of sugars.
  2. Maintain a level of physical activity that achieves fitness and balances energy expenditure with energy intake for weight reduction, expenditure should exceed intake.
  3. Improving cardiorespiratory fitness (CRF- measured as VO2 max using stage tread mill test) may markedly reduce the risk of CVD.

Certainly, starvation, very-low-calorie diets, liquid protein diets, and obesity surgeries have been associated with prolongation of the QTc interval and increased risk of malignant dysrhythmias , and various pharmacologic agents have either limited efficacy or considerable toxicity.39

Clearly lifestyle interventions, including exercise training and at least mild weight reduction with caloric restriction stands a choice. The most studied nonpharmacologic therapy in CV disease for weight reduction has been cardiac rehabilitation and exercise training, which resulted in a 37% reduction in the prevalence of metabolic syndrome.40

In HTN, weight reduction has resulted in significant decreases in arterial pressure.3 MacMahon et al.41 showed that even an 8-kg weight loss resulted in small but statistically greater reductions in LV wall thickness in mildly obese hypertensive patients compared with standard pharmacologic intervention.
In HF, despite the obesity paradox, trials have suggested that weight loss can induce improvements in LV mass as well as in systolic and diastolic ventricular function.13

Currently, many severely obese patients are being considered for various obesity surgical procedures.Although 30-day mortality after gastric bypass has recently been reported to be higher than expected, closely linked to surgeon inexperience,42 more studies are now showing that these surgical procedures are associated with short- and long-term improvements in major morbidity and all-cause mortality, particularly related with cancers, DM, and CV diseases, and also predict long-term decreases in CV risk in obese patients (81). Obesity surgery may reduce arterial pressure over the short term (2 to 3 years), but may not have a long-term (e.g., 6 to 8 years) effect to reduce HTN.43 Large-scale studies are needed on the risks and benefits of obesity surgeries in patients with advanced CV diseases, including HTN, CHD, HF, and AF; a recent small study suggests that bariatric surgery is safe and effective in patients with severe systolic HF.44

Fitness is a single measure that is influenced by many factors, including age, heredity, and recent and lifelong activity patterns. Several studies have demonstrated that fitness is a stronger predictor of mortality than BMI and that higher fitness eliminated the mortality risk of elevated BMI (the fat-but-fit hypothesis).45 The Veterans Exercise Testing Study (VETS) as recorded on a tread mill affords a unique opportunity to study simultaneous measures of fitness and adiposity in a large patient population exhibiting an obesity paradox. Peak exercise time is recorded in minutes. Peak workload is estimated as metabolic equivalents (METs). One MET is defined as the energy expended at rest, which is equivalent to an oxygen consumption of 3.5 mL · kg-1 · min?1. Physical activity comprising of- 30 min aerobic exercise(fast walking ,running, ball games or swimming) at a heart rate corresponding to 55% to 65% of individual maximal cardiorespiratory fitness followed by 20 min of strengthening exercise of arms, legs and trunk,10 min of stretching and cool down improves cardio respiratory function (CRF). Improving CRF may markedly reduce the risk of CVD among obese people.

Overweight and obese subjects often develop dyslipidemia, elevated blood pressure, metabolic syndrome/diabetes, increased levels of inflammation, and structural and functional alterations of the heart and vasculature that lead to substantial CVD. Part of the explanation of the obesity paradox has been blamed on the limitations of the BMI assessment of obesity, methods other than BMI (CRF; MET; WC; % body fat) may be better to detect obesity and predict increased medical and CVD risk. Along with efforts at preventing obesity and promoting successful weight reduction, efforts to improve overall physical activity and CRF would go a long way to prevent CVD.