Author + information
- Ulrich Kintscher, MD∗ ()
- Pharmacology and Metabolic Research, Charité-Universitaetsmedizin Berlin, Center for Cardiovascular Research, Institute of Pharmacology, Berlin, Germany
- ↵∗Reprint requests and correspondence:
Dr. Ulrich Kintscher, Pharmacology and Metabolic Research, Charité-Universitaetsmedizin Berlin, Center for Cardiovascular Research, Institute of Pharmacology, Hessische Strasse 3-4, Berlin 10115, Germany.
At first glance, obesity seems to be clearly associated with an increased risk for cardiovascular (CV) events, CV death, and even all-cause death. This has been proven in numerous studies investigating this relationship in patients without prior CV events (1). However, there is increasing evidence that the association between body mass index (BMI) and CV morbidity/mortality or all-cause mortality is reversed in selected patient populations, in particular in patients with previous CV events. This phenomenon has been named the “obesity paradox.” In detail, the obesity paradox states that under certain conditions such as chronic heart failure, an elevated BMI positively correlates with improved prognosis or decreased risk (2). Previously, the paradox has been only described in regional cohorts. Furthermore, it appears that the paradox may largely apply to distinct subgroups of patients; however, robust data for subgroup identification are still missing.
In this issue of the Journal, Shah et al. (3) studied the obesity paradox in 6,142 patients with acutely decompensated heart failure from 12 prospective observational cohorts across 4 continents. The analysis comprised patients with acute decompensated heart failure including those with new onset heart failure and those with acute cardiac decompensation of chronic failure from 8 European studies, 2 North American studies, 1 Asian study, and 1 study from South America. The population was stratified into 3 BMI categories: normal weight (BMI: 18.5 to 25 kg/m2), overweight (BMI: 25 to 30 kg/m2), and obese (BMI: ≥30 kg/m2), and as the primary outcome, all-cause mortality was analyzed at 30 days and 1 year of follow-up by medical chart review.
Baseline characteristic of the study population revealed that normal weight patients were older, with more severe heart failure, less comorbidities (e.g., diabetes, hypertension), and lower prescription rates of cardiovascular drugs such as beta-blockers, blockers of the renin-angiotensin system, and statins. The investigators applied a Cox proportional hazards model and net reclassification index to describe the association between BMI and the primary outcome. In consonance with recently published data, a higher BMI was associated with a decreased 30-day mortality in an unadjusted model but not in the fully adjusted model, and more importantly, long-term mortality (1 year) was reduced in higher BMI categories using both statistical models. These results confirm the notion that in acute heart failure, a higher BMI particularly improves long-term prognosis. Worth mentioning is the regional heterogeneity of the study population corroborating the existence of a global obesity paradox. An even more important piece of data is presented in the further analysis of the data focusing on subgroup identification. Shah et al. (3) report that a higher BMI is associated with lower mortality particularly among older patients more than 75 years of age, in patients with reduced ejection fraction, in patients without diabetes, and in patients with de novo acute heart failure on admission.
The identification of selected subgroups in whom the obesity paradox is particularly applicable provides an important contribution to the controversially discussed existence of the paradox in heart failure (2,4). Looking at these data one may conclude that both sides of the controversy are justified. The obesity paradox does not apply to the general population of patients with acute decompensated heart failure. But looking through the glasses of an “individualized medicine,” the paradox seems to exist for selected patients: nondiabetic, older patients with reduced cardiac function and de novo heart failure.
With respect to the present study, one of the most important questions remains: Do these findings translate into clinical or therapeutic practice? In the case of future confirmatory data, subgroup characterization should definitely determine future individualized therapeutic approaches. With a focus on acute/chronic heart failure, one should identify patient subpopulations who benefit from body weight reduction, patients who benefit from body weight maintenance, and patients who benefit from body weight gain or a positive energy balance. Independent of the more “academic” discussion about the existence of the obesity paradox, future prospective interventional studies need to center around practical solutions for an individualized body weight/energy balance–guided supportive therapy for heart failure. The study by Shah et al. (3) may act as a kick off.
One limitation of the present study that requires further discussion comes from the more general question, whether BMI alone is an adequate parameter to address the complex interactions between obesity and CV risk? BMI has been used in most of the published studies investigating the obesity paradox. As previously pointed out by other investigators (5), BMI includes multiple metabolic measures including fat mass, lean or fat-free mass, water, and so forth, and seems to be a rather inaccurate parameter. To do justice to the complex metabolic processes involved in obesity-mediated CV disease progression/regression, a more precise parameter/technique for body composition such as magnetic resonance imaging or dual-energy X-ray absorptiometry should be tested in future studies (6,7). In addition to the relevance of body composition, cardiorespiratory fitness has been recently pointed out as a more relevant CV risk predictor than BMI alone (8). Along this line, cardiorespiratory fitness has already been investigated as an additional important determinant for the relationship between overweight/obesity and CV risk in the context of the obesity paradox (5).
Taken together, it appears that a global individualized obesity paradox exists. However, future prospective and even interventional studies using advanced metabolic measures are absolutely required to finally develop metabolically guided supportive therapy for heart failure patients.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Kintscher has reported that he has no relationships relevant to the contents of this paper to disclose.
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