doi: 10.1161/CIRCULATIONAHA.107.716662
(Circulation. 2007;116:588-590.)
© 2007 American Heart Association, Inc.
Editorial |
Tipping the Scale
Heart Failure, Body Mass Index, and Prognosis
From the Division of Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow Klinikum, Berlin, Germany (S.v.H., S.D.A.), and Ahmanson–UCLA Cardiomyopathy Center, University of California at Los Angeles Medical Center, Los Angeles (T.B.H., G.C.F.).
Correspondence to Professor Stefan D. Anker, Division of Applied Cachexia Research, Department of Cardiology, Charité, Campus Virchow-Klinik, Augustenburger Platz 1, D-13353 Berlin, Germany. E-mail s.anker{at}cachexia.de
Key Words: Editorials • heart failure • obesity • prognosis
Obesity has reached endemic proportions. The World Health Organization has estimated that >1 billion adults are overweight worldwide, and 300 million of them are clinically obese.1 In the general population up to 60 to 65 years of age, a higher body mass index (BMI) is associated with an increased risk for cardiovascular events and new-onset heart failure (HF). An increasing number of patients with chronic illness are obese. Of patients with chronic HF, >50% are in the overweight or obese categories.2 Although it was presumed that obesity would further increase mortality risk in patients with established HF, a number of recent studies have indicated that BMI is actually inversely associated with long-term mortality in chronic HF, the so-called obesity paradox.3
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In this issue of Circulation, a retrospective analysis of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) trial program by Kenchaiah et al4 on the relationship between BMI and survival and other important clinical end points is reported. The authors analyzed data from all 7599 patients with symptomatic chronic HF who received candesartan (n=3803) or placebo (n=3796) and who were either angiotensin-converting enzyme inhibitor naïve or already treated with such a drug. Patients were in New York Heart Association classes II through IV, and their left ventricular ejection fractions were distributed across a wide range, with a mean value of 39%. All subjects were followed up for a median of 37.7 months. Kenchaiah et al subgrouped the patients according to different BMI categories, with those with a BMI between 30.0 and 34.9 kg/m2 serving as the reference group because these patients had the overall lowest mortality. This is an important qualitative difference from most other articles on the subjects. Commonly, BMI subgroups that were thought to represent "normal" weight (with BMIs of 20.0 to 24.9 or 18.5 to 24.9 kg/m2) were chosen as the reference group, which first implies the presence of no excess risk in these patients and second may understate the true mortality risk from being underweight.
The CHARM authors report a progressive increase in mortality below a BMI of 30.0 kg/m2 and found a plateau or small increase above a BMI of 34.9 kg/m2. These data, once again, buttress the view that the BMI-mortality relationship in patients with chronic HF and other cardiovascular diseases is U shaped. Rather, this relationship is linear up to a BMI of 35 kg/m2 and overall likely J shaped. Kenchaiah et al have extended our knowledge on the favorable association of obesity with improved prognosis in chronic HF in 2 important populations: patients with a BMI as high as 35 kg/m2 and patients with a very large range of LVEF values and, in particular, those with nonsystolic HF (ie, HF with preserved ejection fraction). A large proportion of patients in CHARM received ß-blockers besides angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers; hence, the results presented in that article are generalizable to contemporary HF populations.
It remains a matter of speculation why patients with chronic HF who are overweight, moderately obese, or even severely obese survive better than those who are, by all standard definitions, without this traditional cardiovascular risk factor. There are a number of possible explanations. One is that many obese patients with shortness of breath are more often than other patients misdiagnosed with regard to the presence of HF. It is a truism that ill patients are ill and die early, but the reverse is true as well. A number of obese patients may simply not have HF and hence survive (on average) somewhat better. This notion is supported by the fact that several studies analyzing brain natriuretic peptide and N-terminal pro B-type natriuretic peptide have found that obese patients with HF have surprisingly low plasma levels of these natriuretic peptides.5 This may result in part because of some problems in reliably measuring brain natriuretic peptide fragments in obese patients, but also some obese patients could, despite expert input into the gold standard diagnosis of HF, be misdiagnosed and simply may not have HF as indicated by their low brain natriuretic peptide or N-terminal pro B-type natriuretic peptide. However, because the relationship between BMI and mortality has been shown to be independent of left ventricular function and multiple other prognostic factors in multiple studies, this cannot be the entire explanation for these observations.
Among patients with cardiovascular illness, the finding that obese patients fare prognostically better than nonobese patients is not restricted to patients with chronic HF (see the Figure). Indeed, in other chronic illnesses like chronic obstructive pulmonary disease, cancer, renal failure, or liver cirrhosis, obese patients show better survival.6 This cannot be due entirely to obesity causing misdiagnosis. Obesity must be a marker of something positive if it is not itself of benefit. Obese patients have more adipose tissue. Fat contains twice as much energy as protein or carbohydrates. Hence, fat tissue is an energy reserve. Patients with HF (as with any chronic illness) are exposed to catabolic metabolic changes, including inflammation and activation of stress hormone systems.7 Under the assumption that tissue wasting (in most chronically ill patients) occurs sooner or later, then obese patients have more reserves and can "last" longer. Being overweight or obese is then a sign of having sufficient metabolic reserves and having not yet wasted. Furthermore, obesity also is associated with somewhat higher skeletal muscle mass. Because of adjustments for overall body weight, standard tests to assess exercise capacity in obese patients routinely underestimate true exercise capacity.8 Thus, adjustment for lean muscle mass, as opposed to total body weight, yields more accurate results and should be preferable whenever possible.9
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It is also possible that adiposity and increased serum cholesterol levels in patients with HF are beneficial because the adipocytes and lipoprotein pool serve as effective scavengers to bind with and neutralize circulating lipopolysaccharides, including bacterial endotoxin.10 Other components of adipokine physiology in obese patients with HF may be an important part of the obesity paradox. Kistorp et al11 found that lower adiponectin levels (which occur in the setting of an increased BMI) predicted improved survival in patients with compensated HF.
This raises the possibility that obesity in HF and in chronic illness generally can be protective per se. Further research clearly is needed to elucidate the mechanisms by which a higher BMI may produce a protective effect in patients with HF. These studies raise the possibility that a therapeutic approach in providing nutritional/metabolic support for patients with chronic HF has the potential to affect survival favorably. Randomized clinical trials of strategies to improve nutritional/metabolic status in patients with HF who have a BMI <28 kg/m2 should be considered.
However we look at the data on hand, there can be no doubt that the presence of obesity in patients with chronic HF is associated with longer survival, although not necessarily with better quality of life.12 Thus, from a prognostic standpoint, up to fairly high BMI values, recommending weight loss in chronic HF patients seems not to be an easily justifiable option. It also has been shown that weight loss in HF independently of the patient’s BMI and intentions carries adverse prognostic information.13 No reliable statement can be made for patients with a BMI >40 kg/m2 because their number in existing studies is too small. It is also important to note that the prognosis of obese patients with HF is comparatively very good and hence that the survival time gain as a result of heart transplantation could be fairly small in obese patients.14
It is now well established that in patients with symptomatic HF with reduced or preserved left ventricular systolic function, elevated BMI is associated with a better prognosis. It seems time to comprehensively revisit our thinking about obesity, especially in the context of chronic illnesses. The prognostic implications and hence the pathophysiological consequences of obesity in (mostly older) patients with chronic illness appear to be completely different from obesity in young people without illness. The knowledge gained and recommendations derived from 1 group cannot be transferred by conjecture to the other group. A clearer understanding of the mechanisms for the relationship between HF, adiposity, and clinical outcomes may lead us to new therapeutic strategies allowing further gains against the lethal disease state of HF.
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Acknowledgments |
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Disclosures
None.
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Footnotes |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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References |
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