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Association between body mass index and long-term clinical outcomes in patients with non-valvular atrial fibrillation taking oral anticoagulants

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Abstract

Background and aims

The association between body mass index (BMI) and clinical outcomes of patients with non-valvular atrial fibrillation (NVAF) taking oral anticoagulants (OACs) are controversial, and we thus analyzed the large registry data to elucidate them.

Methods and results

We conducted a historical cohort study at 71 centers in Japan and included outpatients with NVAF taking vitamin K antagonists (VKAs). Physicians in charge could change VKAs to direct OACs based on their judgement during follow-up period. We categorized patients into four BMI groups (kg/m2): underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (30 ≤ BMI). The effects of each BMI group relative to the normal weight group on clinical outcomes consisting of all-cause death, ischemic events, and bleeding events were estimated using Cox proportional hazard models adjusting for potential confounders. We also constructed restricted cubic spline regression model adjusted by multivariable Cox proportional hazard models. We included 6927 patients consisting of an underweight (n = 386), normal weight (n = 3785), overweight (n = 2174), and obese (n = 582) groups. The median follow-up period was 3.9 years. In the underweight group, the adjusted hazard ratios (HRs) for all-cause death and ischemic events were 1.75 (1.30–2.34) and 1.61 (1.04–2.50). The HR for all-cause death was 0.63 (0.49–0.82) in the overweight group. Restricted cubic spline regression models confirmed that lower BMI showed significantly higher risks for all-cause death and ischemic events.

Conclusion

Among NVAF patients taking OACs, underweight patients had higher risks of all-cause death and ischemic events than other patients. Overweight patients had lower risk of all-cause death.

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Data availability statement

The data supporting the study are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was supported by Bristol-Myers Squibb and JSPS KAKENHI (JP21H03176). The funders did not participate in any part of the study from conception to article preparation. We are indebted to the data managers of the Institute for Clinical Effectiveness (Ms. Makiko Ohtorii, Ms. Ai Sunagawa, Ms. Kaori Yamamoto, Ms. Sachiko Kitamura, Ms. Hirono Saito, and Ms. Saeko Nagano) for managing the data and performing the statistical analyses.

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan

    Mari Nezu, Kazutaka Uchida, Fumihiro Sakakibara, Norito Kinjo, Hideki Arai & Takeshi Morimoto

  2. Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan

    Shinichiro Ueda

  3. Department of Neurosurgery, Hyogo Medical University, Nishinomiya, Japan

    Kazutaka Uchida, Fumihiro Sakakibara & Norito Kinjo

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  1. Mari Nezu
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Contributions

MN: study conception, design, statistical analyses, interpretation of the data, and drafting the manuscript. SU: study conception, design, data acquisition and management, interpretation of the data, and critical revision of the manuscript. KU: interpretation of the data, and critical revision of the manuscript. FS: interpretation of the data, and critical revision of the manuscript. NK: interpretation of the data, and critical revision of the manuscript. HA: interpretation of the data, and critical revision of the manuscript. TM: study conception, design, data acquisition and management, statistical analyses, interpretation of the data, and drafting of the manuscript.

Corresponding author

Correspondence to Takeshi Morimoto.

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Conflict of interest

Shinichiro Ueda reports receiving a research grant from Bristol-Myers Squibb, Chugai, Kowa, MSD, Pfizer, and Takeda, lecturer’s fees from Boehringer Ingelheim, MSD, and Taiho, and manuscript fees from Kowa. He served on an advisory board for Otsuka. Kazutaka Uchida reports lecturer’s fees from Daiichi Sankyo. Takeshi Morimoto reports lecturer's fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Toray, and Tsumura; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Novartis and Teijin. Mari Nezu, Fumihiro Sakakibara, Norito Kinjo, and Hideki Arai have no disclosures to report.

Ethical approval

The institutional review boards of University of the Ryukyus (No. 597) and all 71 participating centers approved the study protocol (Online Resource Table 1). The institutional review boards waived the need for written informed consent and approved the study in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan.

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Nezu, M., Ueda, S., Uchida, K. et al. Association between body mass index and long-term clinical outcomes in patients with non-valvular atrial fibrillation taking oral anticoagulants. Heart Vessels 38, 551–561 (2023). https://doi.org/10.1007/s00380-022-02194-w

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