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Reply to ‘Body mass index and the risk of all-cause mortality among patients with nonvalvular atrial fibrillation: a multicenter prospective observational study in China; methodological issues’

European Journal of Clinical Nutrition volume 71, pages 1024–1025 (2017)Cite this article

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We were glad to receive the comments from professor Karamzad and his colleague, regarding our recently published article.1 First, they express concerns about all-cause mortality defined as the primary outcome in our study, and point out that paradoxical association between body mass index (BMI) and all-cause mortality risk may be due to heterogeneity of associations between BMI and cause-specific deaths. In fact, the definition of all-cause mortality as the primary outcome in our study is largely based on the clinical significance and professional perspective, rather than on account of statistical considerations, as all-cause mortality risk is measured to provide holistic impressions of various BMI levels on the survival of patients with nonvalvular atrial fibrillation (NVAF). In addition, as a hard endpoint, all-cause mortality is widely used as the primary outcome in clinical studies to evaluate the effect of various BMI levels among patients with diverse conditions and diseases, for instance, patients suffering from diabetes mellitus,2 patients receiving transcatheter aortic valve implantation,3 and hospitalized patients with pneumonia,4 etc.

Nevertheless, we make further analysis to explore the associations between BMI and cause-specific deaths, according to the proposal raised by professor Karamzad and his colleague. As shown in Table 1, homogeneous associations were indicated between BMI and both cardiovascular and non-cardiovascular deaths, with notably lower risk observed in patients with higher BMI. Specifically, favorable cardiovascular prognosis related to higher BMI is mainly derived from significantly lower risk of sudden cardiac death and deaths from stroke, and for non-cardiovascular causes, the benefit might be due to less deaths caused by infection. In the following survival analysis, we explore the separate impact of BMI on cardiovascular and non-cardiovascular mortality, but not assess every impact of BMI on each cause-specific deaths using hierarchical regression models,5 as from the clinical point of view, we find limited value can be provided by performing such analysis, and the combined or aggregated outcome strategy also seems reasonable as homogeneous associations between BMI with cause-specific deaths is indicated in the primary analysis. In multivariable models, paradoxical associations are weakened and even disappeared when BMI is analyzed as categorical variable (Supplementary Table 1), while significant lower cardiovascular risk related to higher BMI exists when analyzed as continuous variable (Supplementary Table 2), indicating that the phenomenon of obesity paradox seems tenable, particularly for cardiovascular deaths, among patients with NVAF.

Table 1 Specific causes of death categorized by body mass index in patients with non-valvular atrial fibrillation
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References

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Acknowledgements

We thank Professor Yang Wang for his great help and guidance with the statistical matters involved in the current study.

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Author notes

  1. S Wu and H Wan: These authors contributed equally to this work.

Authors and Affiliations

  1. Emergency and Intensive Care Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    S Wu, J Wang, Y Yang, J Zhu, X Shao, B Huang & H Zhang

  2. Department of Cardiology, First Affiliated Hospital, Jinan University, Guangzhou, China

    H Wan

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  1. S Wu
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Correspondence to Y Yang.

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Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website

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Wu, S., Wan, H., Wang, J. et al. Reply to ‘Body mass index and the risk of all-cause mortality among patients with nonvalvular atrial fibrillation: a multicenter prospective observational study in China; methodological issues’. Eur J Clin Nutr 71, 1024–1025 (2017). https://doi.org/10.1038/ejcn.2017.14

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