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Oskar Angerås, Per Albertsson, Kristjan Karason, Truls Råmunddal, Göran Matejka, Stefan James, Bo Lagerqvist, Annika Rosengren, Elmir Omerovic, Evidence for obesity paradox in patients with acute coronary syndromes: a report from the Swedish Coronary Angiography and Angioplasty Registry, European Heart Journal, Volume 34, Issue 5, 1 February 2013, Pages 345–353, https://doi.org/10.1093/eurheartj/ehs217
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Abstract
The obesity paradox refers to the epidemiological evidence that obesity compared with normal weight is associated with counter-intuitive improved health in a variety of disease conditions. The aim of this study was to investigate the relationship between body mass index (BMI) and mortality in patients with acute coronary syndromes (ACSs).
We extracted data from the Swedish Coronary Angiography and Angioplasty Registry and identified 64 436 patients who underwent coronary angiography due to ACSs. In 54 419 (84.4%) patients, a significant coronary stenosis was identified, whereas 10 017 (15.6%) patients had no significant stenosis. Patients were divided into nine different BMI categories. The patients with significant stenosis were further subdivided according to treatment received such as medical therapy, percutaneous coronary intervention (PCI), or coronary artery by-pass grafting. Mortality for the different subgroups during a maximum of 3 years was compared using Cox proportional hazards regression with the lean BMI category (21.0 to <23.5 kg/m2) as the reference group. Regardless of angiographic findings [significant or no significant coronary artery disease (CAD)] and treatment decision, the underweight group (BMI <18.5 kg/m2) had the greatest risk for mortality. Medical therapy and PCI-treated patients with modest overweight (BMI category 26.5–<28 kg/m2) had the lowest risk of mortality [hazard ratio (HR) 0.52; 95% CI 0.34–0.80 and HR 0.64; 95% CI 0.50–0.81, respectively]. When studying BMI as a continuous variable in patients with significant CAD, the adjusted risk for mortality decreased with increasing BMI up to ∼35 kg/m2 and then increased. In patients with significant CAD undergoing coronary artery by-pass grafting and in patients with no significant CAD, there was no difference in mortality risk in the overweight groups compared with the normal weight group.
In this large and unselected group of patients with ACSs, the relation between BMI and mortality was U-shaped, with the nadir among overweight or obese patients and underweight and normal-weight patients having the highest risk. These data strengthen the concept of the obesity paradox substantially.
- acute coronary syndromes
- angiogram
- obesity
- percutaneous coronary intervention
- coronary angiography
- coronary arteriosclerosis
- coronary artery
- body mass index procedure
- survival analysis
- coronary stenosis
- constriction, pathologic
- mortality
- transplantation
- underweight
- interval data
- swedish coronary angiography and angioplasty registry
- overweight
- medical management
Comments
In their letter, Dr. Carpeggiani and colleagues argue against the existence of obesity paradox as a general comment to our paper by Angeras et al.(1). In support of this claim, the authors offer the data and conclusions from their own recent publication(2). There are several issues in relation to this claim that need to be examined in detail. The paper by Iozzo et al.(2) is based on observational data from 10,446 patients included over a period of 30-years. The authors clearly demonstrated with their primary analysis that the lowest risk of death was in overweight and obese individuals when all patients were included in the analysis. The authors then divided the population into two age categories, (<65 and >65 years) and into patients who were hospitalized before and after 1990. While presence of obesity paradox was still present in patients > 65 and in patients included after 1990, this was not the case in patients <65. The authors concluded that this secondary analysis based on subgroups was central to prove that obesity paradox may be explained by residual confounding due to overrepresentation of younger patients and to better medical treatment in this patient category. We are not convinced by the arguments offered by Dr. Carpeggiani against obesity paradox.
We believe that their findings can be interpreted in a radically different way. Decreasing the sample size due to the partition of the population according to age and "time-epochs" results in substantial loss of statistical power to detect a relation between the variable and patient outcome. This loss of power is further worsened by categorization of the continuous BMI variable. If we assume that the younger population had lower mortality (the authors have not reported on number of deaths in the subgroups) with lower event-rate per BMI category in younger patients, this will further aggravate an already substantial power problem. Giving all these concerns we argue that the reason for lack of obesity paradox in younger patients may be solely related to the type- II error in statistical inference. If the authors wanted to investigate "effect-modification" between different variables (e.g. between age and BMI and "time-epochs" and BMI) they should have used the test for interaction between the (prespecified) subgroups which is the recommended approach(3) or alternatively apply the similar method as we did. Our statistical approach to test the possible interaction between age and BMI in Swedish Coronary Angiography and Angioplasty Registry (SCAAR) population was the model based on fractional polynomial Cox regression(4) where BMI was kept as a continuous variable adjusted for other confounders in an analysis that included all patients. While U-shaped relationship between BMI and risk of death was clearly demonstrated, no significant interaction was found between BMI and age. This later finding represents the lack of "effect modification" of age on BMI in our study. Obesity paradox has been reported by several independent investigators(5,6) in different patient populations. Angeras et al.(1) confirm this epidemiological phenomenon in patients with acute coronary syndrome based on the large population from SCAAR. Indeed, we argue that Iozzo et al. not only have not disproved the concept of the obesity paradox but also that their (most important) data from the primary analysis clearly supports the obesity paradox.
References
1. Angeras O, Albertsson P, Karason K, Ramunddal T, Matejka G, James S, Lagerqvist B, Rosengren A, Omerovic E. Evidence for obesity paradox in patients with acute coronary syndromes: A report from the swedish coronary angiography and angioplasty registry. European heart journal. 2013;34:345- 353
2. Iozzo P, Rossi G, Michelassi C, Landi P, Carpeggiani C. Interpretation of the "obesity paradox": A 30-year study in patients with cardiovascular disease. International journal of cardiology. 2012
3. Sun X, Briel M, Walter SD, Guyatt GH. Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. Brit Med J. 2010;340
4. Royston P, Ambler G, Sauerbrei W. The use of fractional polynomials to model continuous risk variables in epidemiology. International journal of epidemiology. 1999;28:964-974
5. Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG, Mookadam F, Lopez-Jimenez F. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: A systematic review of cohort studies. Lancet. 2006;368:666-678
6. Oreopoulos A, McAlister FA, Kalantar-Zadeh K, Padwal R, Ezekowitz JA, Sharma AM, Kovesdy CP, Fonarow GC, Norris CM. The relationship between body mass index, treatment, and mortality in patients with established coronary artery disease: A report from approach. European heart journal. 2009;30:2584-2592
Conflict of Interest:
None declared
Oscar Angeras and colleagues (1) concluded that overweight and obese patients with acute coronary syndrome had lower mortality rate compared with patients with normal body mass index (BMI). This was independent of the treatment strategy until up to 3 years after hospitalization.
The results are not in line with those of a previous investigation which showed that no independent relationship was found between BMI and mortality in subjects ?65 years of age and that this neutral relationship seemed to be partly counteracted by treatment, particularly in old patients (2). Iozzo and colleagues using a population of 10,446 cardiac patients, concluded that obesity paradox might be the results of confounding parameters. In particular the subdivision of subjects according to age categories and treatment epochs was identified as a key strategy to examine and to prove the inconsistency of the obesity paradox in patients requiring hospitalization for heart disease of various origins. Overweight and obesity were not protective in the?65 age group, whereas the obesity showed a protective effect in older patients, exposed to a different intensiveness of drug treatment and multiple therapy associations presenting more secondary diseases, such as diabetes and/or hypertension. Authors also suggested a possible different effects of late versus early onset obesity.
We think, therefore, that it would be important in Angeras study to clarify whether the same results would be obtained in young compare to old patients and whether the results would be affected by different prevalence of revascularizations in young compare to old patients, who apparently were more likely to be lean and to have prevalence of coronary dilatations.
References
1 Angeras O, Albertsson P, Karason K et al. Evidence for obesity paradox in patients with acute coronary syndromes: a report from the Swedish Coronary Angiography and Angioplasty Registry. European Heart J 2013;34:345-353.
2 Iozzo P, Rossi G, Michelassi C, Landi P, Carpeggiani C. Interpretation of the "obesity paradox": A 30-year study in patients with cardiovascular disease. Intern J of Cardiol 2012. IJCA-15238.
Conflict of Interest:
None declared