Obesity Paradox, Cachexia, F r a i l t y, a n d H e a r t Fa i l u re Carl J. Lavie, MDa,b,c,*, Alban De Schutter, MDa, Martin A. Alpert, MDd, Mandeep R. Mehra, MDe, Richard V. Milani, MDa, Hector O. Ventura, MDa KEYWORDS Obesity Heart failure Cachexia Frailty
KEY POINTS Overweight and obesity adversely affect hemodynamics and ventricular structure and function, and greatly increase the prevalence of heart failure (HF). An obesity paradox exists, because overweight and obese patients with HF, by body mass index, body fat, and waist circumference, seem to have a better prognosis than do their leaner counterparts with HF. Frailty and cardiac cachexia are associated with poor clinical prognosis in many conditions, including HF. Low levels of cardiorespiratory fitness (CRF) are associated with a poor prognosis in HF and, in this group, as opposed to patients with HF with better CRF, a strong obesity paradox exists, with the leaner patients with low CRF having a particularly poor prognosis. Purposeful weight loss in HF remains controversial, although this therapy seems warranted, especially with severe obesity.
Despite the adverse affects of obesity on CV risk factors and the development of CV disease, including HF, numerous studies have shown an obesity paradox, meaning that overweight and obese patients with HF have a better prognosis than do their leaner counterparts, with the leanest patients with HF, including the frail and cachectic,2–4 having a particularly poor prognosis. This article describes the hemodynamic effects of weight on CV structure and function, and addresses the impact of overweight/obesity on the incidence and prevalence of HF. It also describes
a Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University of Queensland School of Medicine, 1514 Jefferson Highway, New Orleans, LA 70121-2483, USA; b Cardiac Rehabilitation, Exercise Laboratories, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University of Queensland School of Medicine, 1514 Jefferson Highway, New Orleans, LA 70121-2483, USA; c Department of Preventive Medicine, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA; d Division of Cardiovascular Medicine, University of Missouri School of Medicine, Room CE-338, 5 Hospital Drive, Columbia, MO 65202, USA; e BWH Heart and Vascular Center and Harvard Medical School, Brigham and Women’s Hospital, 75 Francis Street, A Building, 3rd Floor, Room AB324, Boston, MA 02115, USA * Corresponding author. Cardiac Rehabilitation, Exercise Laboratories, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University of Queensland School of Medicine, 1514 Jefferson Highway, New Orleans, LA 70121-2483. E-mail address: [email protected]
Heart Failure Clin 10 (2014) 319–326 http://dx.doi.org/10.1016/j.hfc.2013.12.002 1551-7136/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
heartfailure.theclinics.com
Overweight and obesity, which are typically defined by body mass index (BMI) criteria, have numerous adverse effects on general, and particularly, cardiovascular (CV), health.1,2 Obesity is a major risk factor for both coronary heart disease (CHD) and hypertension (HTN), which are the two strongest risk factors for development of heart failure (HF). In addition, obesity adversely affects CV structure and function, causing systolic, and especially diastolic, left ventricular (LV) dysfunction. Therefore, overweight and obesity are potent risk factors for the development of HF.2
320
Lavie et al the obesity paradox, and especially the adverse effects of cachexia and frailty on HF prognosis. In addition, potential implications of weight loss and exercise training (ET; aerobic/dynamic, as well as isometric/resistance) for the treatment of HF are discussed, particularly in frail and/or cachectic patients.
Box 1 Effects of obesity on cardiac performance 1. Hemodynamics i. Increased blood volume ii. Increased stroke volume iii. Increased arterial pressure
IMPACT OF OBESITY ON HEMODYNAMICS AND VENTRICULAR STRUCTURE AND FUNCTION We recently reviewed the detailed evidence showing the adverse affects of overweight/obesity on central and peripheral hemodynamics, as well as on cardiac structure and function (Box 1, Fig. 1).2 Although the impact of obesity on LV structure and function are well recognized, the right ventricle is also adversely affected by obesity, especially morbid obesity. Cardiac cachexia in chronic HF with systolic dysfunction was recently associated with right ventricular (RV) dysfunction independent of LV systolic dysfunction, which correlates with cachexia and prognosis.4,5 Fat mass loss rather than lean body mass loss was noted in this study, a finding that is counter to conventional understanding. It may be that fat loss represents an earlier event as cachexia becomes manifest, a finding that may be used to assess prognosis at a time when the syndrome may be influenced therapeutically, although this contention remains speculative.
iv. Increased LV wall stress v. Pulmonary artery hypertension 2. Cardiac structure i. LV concentric remodeling ii. LV hypertrophy (eccentric and concentric) iii. Left atrial enlargement iv. RV hypertrophy 3. Cardiac function i. LV diastolic dysfunction ii. LV systolic dysfunction iii. RV failure 4. Inflammation i. Increased C-reactive protein ii. Overexpression of tumor necrosis factor 5. Neurohumoral i. Insulin resistance and hyperinsulinemia ii. Leptin insensitivity and hyperleptinemia iii. Reduced adiponectin iv. Sympathetic nervous system activation
OBESITY AND HF PREVALENCE Substantial data suggest an increase in HF incidence and prevalence in overweight and obesity.2 In 5881 Framingham Heart Study participants, Kenchaiah and colleagues6 showed a 5% increase in HF in men and 7% increase in HF in women for every 1 kg/m2 increase in BMI during a 14-year follow-up; the increase in HF risk was noted across all BMI categories. In a study of 74 morbidly obese patients, nearly one-third had clinical evidence of HF, with the probability of HF increasing greatly with the duration of morbid obesity; prevalence rates exceeded 70% at 20 years and 90% at 30 years.7
v. Activation of aldosterone system
renin-angiotensin-
vi. Overexpression of peroxisome proliferator-activator receptor 6. Cellular i. Hypertrophy ii. Apoptosis iii. Fibrosis Abbreviation: RV, right ventricular. From Lavie CJ, Alpert MA, Arena R, et al. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail 2013;1(2):93–102; with permission.
OBESITY PARADOX AND HF Horwich and colleagues8 were among the first to show an obesity paradox in HF, in that the best prognosis occurred in the overweight patients with HF, followed closely by obese patients with HF based on BMI classification. In contrast, the worst prognosis occurred in the underweight or cachectic patients with HF (who typically have a
poor prognosis in most general health and CV situations) and followed closely by the patients with normal BMI and HF (Fig. 2).8 We previously showed that this obesity paradox was noted with percent body fat (BF) as well as with BMI (Fig. 3),9 because for every 1% increase in percent BF there was a 13% independent reduction in
Obesity Paradox, Cachexia, Frailty, Heart Failure Fig. 1. The central hemodynamic, cardiac structural abnormalities and alterations in ventricular function that may occur in severely obese patients and predispose them to HF. LV hypertrophy in severe obesity may be eccentric or concentric. In uncomplicated (normotensive) severe obesity, eccentric LV hypertrophy predominates. In severely obese patients with long-standing systemic hypertension, concentric LV hypertrophy is frequently observed and may occur more commonly than eccentric LV hypertrophy. Whether and to what extent metabolic disturbances such as lipotoxicity, insulin resistance, leptin resistance, and alterations of the renin-angiotensin-aldosterone system contribute to obesity cardiomyopathy in humans is uncertain. RV, right ventricular. (From Lavie CJ, Alpert MA, Arena R, et al. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail 2013;1(2):93–102; with permission.)
Fig. 2. Risk-adjusted survival curves for the 4 BMI categories at 5 years in a study of 1203 patients with moderate to severe HF. Survival was significantly better in the overweight and obese categories. (From Horwich TB, Fonarow GC, Hamilton MA, et al. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol 2001;38:789–95; with permission.)
major CV events. A recent study by Clark and colleagues10 showed that both higher BMI and higher waist circumference (WC) were associated with better HF event–free survival. In an analysis of inhospital mortality in more than 100,000 patients with decompensated HF, Fonarow and colleagues11 showed that higher BMI was associated with lower in-hospital mortality. In this large study, for every 5-unit increase in BMI, in-hospital mortality was reduced by approximately 10%. In a study of 7599 symptomatic patients with HF with either reduced or preserved systolic function, Kenchaiah and colleagues12 showed that underweight patients and patients with normal BMI have a higher mortality than did overweight and obese patients with HF, but this increased mortality was prominently noted in those without volume overload and peripheral edema. Several years ago, in a large meta-analysis of 9 observational studies of nearly 30,000 patients with HF, Oreopoulos and colleagues13 showed that, compared with patients with HF with normal
321
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Lavie et al
Box 2 Potential reasons for the obesity paradox in HF 1. Nonpurposeful weight loss 2. Greater metabolic reserves 3. Less cachexia 4. Protective cytokines 5. Earlier presentationa 6. Attenuated response to renin-angiotensinaldosterone system 7. Higher blood pressure leading to more cardiac medications 8. Different cause of HF 9. Increased strength
muscle
mass
and
muscular
10. Implications related to cardiorespiratory fitness
Fig. 3. Freedom from cardiovascular death or urgent transplantation in patients in quintiles (Q) 1 and 5 for percent BF (A) and body mass index (B). (From Lavie CJ, Osman AF, Milani RV, et al. Body composition and prognosis in chronic systolic heart failure: the obesity paradox. Am J Cardiol 2003;91:891–4; with permission.)
BMI, those overweight and obese patients with HF had significant reductions in all-cause ( 16% and 33%, respectively) and CV mortality ( 19% and 40%, respectively).
MECHANISMS FOR OBESITY PARADOX IN HF Although there are several potential mechanisms for the obesity paradox in patients with CV diseases and in HF (Box 2),2 the exact reason for this relationship remains difficult to reconcile. HF is a catabolic state, and obese patients may have more metabolic reserve.2 Frail and cachectic patients (discussed later) experience greater morbidity and higher mortality in many disease states, including HF.2,4 Adipose tissue is also known to produce soluble tumor necrosis factoralpha receptors, and this could have a protective effect in overweight and obese patients with greater adipose tissue.14 Other cytokines and neuroendocrine profiles in overweight/obese patients with HF may be protective. Higher levels of circulating lipoproteins in obese patients with HF may bind and then detoxify lipopolysaccharides,
a Caused by lower atrial natriuretic peptide levels, restrictive lung disease, venous insufficiency, and so on. From Lavie CJ, Alpert MA, Arena R, et al. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail 2013;1(2):93–102; with permission.
which play a role in stimulating the release of inflammatory cytokines, which could also protect the obese patient with HF.2,15 Another potential protective effect of overweight and obesity in HF is caused by the reduced expression of circulating natriuretic peptides.2 We showed that obese patients with HF have suppressed B-type natriuretic peptide levels, which could lead to obese patients with HF presenting earlier with volume accumulation occurring at a less severe stage of HF.2,16 Moreover, obese patients in general have an attenuated response to the renin-angiotensin-aldosterone system (RAAS), which may lead to a better HF prognosis.1,2 In theory, because overweight and obesity are known to increase levels of arterial blood pressure, obese patients with HF typically have high levels of blood pressure and more HTN than do their leaner counterparts. Not only are obese patients able to tolerate more cardioprotective medications, they may also be able to do so at higher, more therapeutic doses, including b-blockers, RAAS inhibitors, and aldosterone antagonists.1,2 In addition, as assessed later, various aspects of body composition, including BF and lean or muscle mass, and physical fitness (PF), including both cardiorespiratory fitness (CRF) and muscle
Obesity Paradox, Cachexia, Frailty, Heart Failure fitness (MF), may affect prognosis in many patients with CV diseases, including HF.17,18
IMPACT OF SEVERE OR CLASS III OBESITY Although an obesity paradox exists for most CV diseases, being noted in HTN, atrial fibrillation, and CHD,1 in addition to HF,2 there is also substantial evidence that the degree of obesity significantly influences prognosis.18–22 For example, even in the general population, Flegal and colleagues23 recently analyzed 97 studies of nearly 2.9 million subjects and noted that obese subjects, including all grades, had worse survival than subjects with normal BMI. However optimal survival in this meta-analysis seemed to occur in the overweight BMI group (BMI, 25–30 kg/m2) who had a significantly (6%) lower mortality than did the subjects with normal BMI. In addition, the mildly obese (class I obese with BMI 30–35 kg/m2) also had a 5% lower mortality than did the normal BMI group, which was nearly statistically significant. In patients with CHD, several recent studies suggest that the relationship between adiposity and prognosis may represent more of an overweight paradox or a lean paradox, as opposed to a true obesity paradox.24–26 As shown in the population-based data, overweight patients with CHD also seem to do particularly well. We suggested that a lean paradox may be present, because patients with both a low BF (
KEY POINTS Overweight and obesity adversely affect hemodynamics and ventricular structure and function, and greatly increase the prevalence of heart failure (HF). An obesity paradox exists, because overweight and obese patients with HF, by body mass index, body fat, and waist circumference, seem to have a better prognosis than do their leaner counterparts with HF. Frailty and cardiac cachexia are associated with poor clinical prognosis in many conditions, including HF. Low levels of cardiorespiratory fitness (CRF) are associated with a poor prognosis in HF and, in this group, as opposed to patients with HF with better CRF, a strong obesity paradox exists, with the leaner patients with low CRF having a particularly poor prognosis. Purposeful weight loss in HF remains controversial, although this therapy seems warranted, especially with severe obesity.
Despite the adverse affects of obesity on CV risk factors and the development of CV disease, including HF, numerous studies have shown an obesity paradox, meaning that overweight and obese patients with HF have a better prognosis than do their leaner counterparts, with the leanest patients with HF, including the frail and cachectic,2–4 having a particularly poor prognosis. This article describes the hemodynamic effects of weight on CV structure and function, and addresses the impact of overweight/obesity on the incidence and prevalence of HF. It also describes
a Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University of Queensland School of Medicine, 1514 Jefferson Highway, New Orleans, LA 70121-2483, USA; b Cardiac Rehabilitation, Exercise Laboratories, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University of Queensland School of Medicine, 1514 Jefferson Highway, New Orleans, LA 70121-2483, USA; c Department of Preventive Medicine, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA; d Division of Cardiovascular Medicine, University of Missouri School of Medicine, Room CE-338, 5 Hospital Drive, Columbia, MO 65202, USA; e BWH Heart and Vascular Center and Harvard Medical School, Brigham and Women’s Hospital, 75 Francis Street, A Building, 3rd Floor, Room AB324, Boston, MA 02115, USA * Corresponding author. Cardiac Rehabilitation, Exercise Laboratories, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University of Queensland School of Medicine, 1514 Jefferson Highway, New Orleans, LA 70121-2483. E-mail address: [email protected]
Heart Failure Clin 10 (2014) 319–326 http://dx.doi.org/10.1016/j.hfc.2013.12.002 1551-7136/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
heartfailure.theclinics.com
Overweight and obesity, which are typically defined by body mass index (BMI) criteria, have numerous adverse effects on general, and particularly, cardiovascular (CV), health.1,2 Obesity is a major risk factor for both coronary heart disease (CHD) and hypertension (HTN), which are the two strongest risk factors for development of heart failure (HF). In addition, obesity adversely affects CV structure and function, causing systolic, and especially diastolic, left ventricular (LV) dysfunction. Therefore, overweight and obesity are potent risk factors for the development of HF.2
320
Lavie et al the obesity paradox, and especially the adverse effects of cachexia and frailty on HF prognosis. In addition, potential implications of weight loss and exercise training (ET; aerobic/dynamic, as well as isometric/resistance) for the treatment of HF are discussed, particularly in frail and/or cachectic patients.
Box 1 Effects of obesity on cardiac performance 1. Hemodynamics i. Increased blood volume ii. Increased stroke volume iii. Increased arterial pressure
IMPACT OF OBESITY ON HEMODYNAMICS AND VENTRICULAR STRUCTURE AND FUNCTION We recently reviewed the detailed evidence showing the adverse affects of overweight/obesity on central and peripheral hemodynamics, as well as on cardiac structure and function (Box 1, Fig. 1).2 Although the impact of obesity on LV structure and function are well recognized, the right ventricle is also adversely affected by obesity, especially morbid obesity. Cardiac cachexia in chronic HF with systolic dysfunction was recently associated with right ventricular (RV) dysfunction independent of LV systolic dysfunction, which correlates with cachexia and prognosis.4,5 Fat mass loss rather than lean body mass loss was noted in this study, a finding that is counter to conventional understanding. It may be that fat loss represents an earlier event as cachexia becomes manifest, a finding that may be used to assess prognosis at a time when the syndrome may be influenced therapeutically, although this contention remains speculative.
iv. Increased LV wall stress v. Pulmonary artery hypertension 2. Cardiac structure i. LV concentric remodeling ii. LV hypertrophy (eccentric and concentric) iii. Left atrial enlargement iv. RV hypertrophy 3. Cardiac function i. LV diastolic dysfunction ii. LV systolic dysfunction iii. RV failure 4. Inflammation i. Increased C-reactive protein ii. Overexpression of tumor necrosis factor 5. Neurohumoral i. Insulin resistance and hyperinsulinemia ii. Leptin insensitivity and hyperleptinemia iii. Reduced adiponectin iv. Sympathetic nervous system activation
OBESITY AND HF PREVALENCE Substantial data suggest an increase in HF incidence and prevalence in overweight and obesity.2 In 5881 Framingham Heart Study participants, Kenchaiah and colleagues6 showed a 5% increase in HF in men and 7% increase in HF in women for every 1 kg/m2 increase in BMI during a 14-year follow-up; the increase in HF risk was noted across all BMI categories. In a study of 74 morbidly obese patients, nearly one-third had clinical evidence of HF, with the probability of HF increasing greatly with the duration of morbid obesity; prevalence rates exceeded 70% at 20 years and 90% at 30 years.7
v. Activation of aldosterone system
renin-angiotensin-
vi. Overexpression of peroxisome proliferator-activator receptor 6. Cellular i. Hypertrophy ii. Apoptosis iii. Fibrosis Abbreviation: RV, right ventricular. From Lavie CJ, Alpert MA, Arena R, et al. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail 2013;1(2):93–102; with permission.
OBESITY PARADOX AND HF Horwich and colleagues8 were among the first to show an obesity paradox in HF, in that the best prognosis occurred in the overweight patients with HF, followed closely by obese patients with HF based on BMI classification. In contrast, the worst prognosis occurred in the underweight or cachectic patients with HF (who typically have a
poor prognosis in most general health and CV situations) and followed closely by the patients with normal BMI and HF (Fig. 2).8 We previously showed that this obesity paradox was noted with percent body fat (BF) as well as with BMI (Fig. 3),9 because for every 1% increase in percent BF there was a 13% independent reduction in
Obesity Paradox, Cachexia, Frailty, Heart Failure Fig. 1. The central hemodynamic, cardiac structural abnormalities and alterations in ventricular function that may occur in severely obese patients and predispose them to HF. LV hypertrophy in severe obesity may be eccentric or concentric. In uncomplicated (normotensive) severe obesity, eccentric LV hypertrophy predominates. In severely obese patients with long-standing systemic hypertension, concentric LV hypertrophy is frequently observed and may occur more commonly than eccentric LV hypertrophy. Whether and to what extent metabolic disturbances such as lipotoxicity, insulin resistance, leptin resistance, and alterations of the renin-angiotensin-aldosterone system contribute to obesity cardiomyopathy in humans is uncertain. RV, right ventricular. (From Lavie CJ, Alpert MA, Arena R, et al. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail 2013;1(2):93–102; with permission.)
Fig. 2. Risk-adjusted survival curves for the 4 BMI categories at 5 years in a study of 1203 patients with moderate to severe HF. Survival was significantly better in the overweight and obese categories. (From Horwich TB, Fonarow GC, Hamilton MA, et al. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol 2001;38:789–95; with permission.)
major CV events. A recent study by Clark and colleagues10 showed that both higher BMI and higher waist circumference (WC) were associated with better HF event–free survival. In an analysis of inhospital mortality in more than 100,000 patients with decompensated HF, Fonarow and colleagues11 showed that higher BMI was associated with lower in-hospital mortality. In this large study, for every 5-unit increase in BMI, in-hospital mortality was reduced by approximately 10%. In a study of 7599 symptomatic patients with HF with either reduced or preserved systolic function, Kenchaiah and colleagues12 showed that underweight patients and patients with normal BMI have a higher mortality than did overweight and obese patients with HF, but this increased mortality was prominently noted in those without volume overload and peripheral edema. Several years ago, in a large meta-analysis of 9 observational studies of nearly 30,000 patients with HF, Oreopoulos and colleagues13 showed that, compared with patients with HF with normal
321
322
Lavie et al
Box 2 Potential reasons for the obesity paradox in HF 1. Nonpurposeful weight loss 2. Greater metabolic reserves 3. Less cachexia 4. Protective cytokines 5. Earlier presentationa 6. Attenuated response to renin-angiotensinaldosterone system 7. Higher blood pressure leading to more cardiac medications 8. Different cause of HF 9. Increased strength
muscle
mass
and
muscular
10. Implications related to cardiorespiratory fitness
Fig. 3. Freedom from cardiovascular death or urgent transplantation in patients in quintiles (Q) 1 and 5 for percent BF (A) and body mass index (B). (From Lavie CJ, Osman AF, Milani RV, et al. Body composition and prognosis in chronic systolic heart failure: the obesity paradox. Am J Cardiol 2003;91:891–4; with permission.)
BMI, those overweight and obese patients with HF had significant reductions in all-cause ( 16% and 33%, respectively) and CV mortality ( 19% and 40%, respectively).
MECHANISMS FOR OBESITY PARADOX IN HF Although there are several potential mechanisms for the obesity paradox in patients with CV diseases and in HF (Box 2),2 the exact reason for this relationship remains difficult to reconcile. HF is a catabolic state, and obese patients may have more metabolic reserve.2 Frail and cachectic patients (discussed later) experience greater morbidity and higher mortality in many disease states, including HF.2,4 Adipose tissue is also known to produce soluble tumor necrosis factoralpha receptors, and this could have a protective effect in overweight and obese patients with greater adipose tissue.14 Other cytokines and neuroendocrine profiles in overweight/obese patients with HF may be protective. Higher levels of circulating lipoproteins in obese patients with HF may bind and then detoxify lipopolysaccharides,
a Caused by lower atrial natriuretic peptide levels, restrictive lung disease, venous insufficiency, and so on. From Lavie CJ, Alpert MA, Arena R, et al. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail 2013;1(2):93–102; with permission.
which play a role in stimulating the release of inflammatory cytokines, which could also protect the obese patient with HF.2,15 Another potential protective effect of overweight and obesity in HF is caused by the reduced expression of circulating natriuretic peptides.2 We showed that obese patients with HF have suppressed B-type natriuretic peptide levels, which could lead to obese patients with HF presenting earlier with volume accumulation occurring at a less severe stage of HF.2,16 Moreover, obese patients in general have an attenuated response to the renin-angiotensin-aldosterone system (RAAS), which may lead to a better HF prognosis.1,2 In theory, because overweight and obesity are known to increase levels of arterial blood pressure, obese patients with HF typically have high levels of blood pressure and more HTN than do their leaner counterparts. Not only are obese patients able to tolerate more cardioprotective medications, they may also be able to do so at higher, more therapeutic doses, including b-blockers, RAAS inhibitors, and aldosterone antagonists.1,2 In addition, as assessed later, various aspects of body composition, including BF and lean or muscle mass, and physical fitness (PF), including both cardiorespiratory fitness (CRF) and muscle
Obesity Paradox, Cachexia, Frailty, Heart Failure fitness (MF), may affect prognosis in many patients with CV diseases, including HF.17,18
IMPACT OF SEVERE OR CLASS III OBESITY Although an obesity paradox exists for most CV diseases, being noted in HTN, atrial fibrillation, and CHD,1 in addition to HF,2 there is also substantial evidence that the degree of obesity significantly influences prognosis.18–22 For example, even in the general population, Flegal and colleagues23 recently analyzed 97 studies of nearly 2.9 million subjects and noted that obese subjects, including all grades, had worse survival than subjects with normal BMI. However optimal survival in this meta-analysis seemed to occur in the overweight BMI group (BMI, 25–30 kg/m2) who had a significantly (6%) lower mortality than did the subjects with normal BMI. In addition, the mildly obese (class I obese with BMI 30–35 kg/m2) also had a 5% lower mortality than did the normal BMI group, which was nearly statistically significant. In patients with CHD, several recent studies suggest that the relationship between adiposity and prognosis may represent more of an overweight paradox or a lean paradox, as opposed to a true obesity paradox.24–26 As shown in the population-based data, overweight patients with CHD also seem to do particularly well. We suggested that a lean paradox may be present, because patients with both a low BF (
