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  3. BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants
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Research

BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants

BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i2156 (Published 04 May 2016) Cite this as: BMJ 2016;353:i2156
  1. Dagfinn Aune, PhD student and research associate1 2,
  2. Abhijit Sen, postdoctoral fellow1,
  3. Manya Prasad, resident3,
  4. Teresa Norat, principal research fellow2,
  5. Imre Janszky, professor1,
  6. Serena Tonstad, head physician3,
  7. Pål Romundstad, professor1,
  8. Lars J Vatten, professor1
  1. 1Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
  2. 2Department of Epidemiology and Biostatistics, Imperial College, London, UK
  3. 3Department of Community Medicine, Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India
  4. 4Section of Preventive Cardiology, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital Ullevål, Oslo, Norway
  1. Correspondence to: D Aune, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK d.aune{at}imperial.ac.uk
  • Accepted 24 March 2016

Abstract

Objective To conduct a systematic review and meta-analysis of cohort studies of body mass index (BMI) and the risk of all cause mortality, and to clarify the shape and the nadir of the dose-response curve, and the influence on the results of confounding from smoking, weight loss associated with disease, and preclinical disease.

Data sources PubMed and Embase databases searched up to 23 September 2015.

Study selection Cohort studies that reported adjusted risk estimates for at least three categories of BMI in relation to all cause mortality.

Data synthesis Summary relative risks were calculated with random effects models. Non-linear associations were explored with fractional polynomial models.

Results 230 cohort studies (207 publications) were included. The analysis of never smokers included 53 cohort studies (44 risk estimates) with >738 144 deaths and >9 976 077 participants. The analysis of all participants included 228 cohort studies (198 risk estimates) with >3 744 722 deaths among 30 233 329 participants. The summary relative risk for a 5 unit increment in BMI was 1.18 (95% confidence interval 1.15 to 1.21; I2=95%, n=44) among never smokers, 1.21 (1.18 to 1.25; I2=93%, n=25) among healthy never smokers, 1.27 (1.21 to 1.33; I2=89%, n=11) among healthy never smokers with exclusion of early follow-up, and 1.05 (1.04 to 1.07; I2=97%, n=198) among all participants. There was a J shaped dose-response relation in never smokers (Pnon-linearity <0.001), and the lowest risk was observed at BMI 23-24 in never smokers, 22-23 in healthy never smokers, and 20-22 in studies of never smokers with ≥20 years’ follow-up. In contrast there was a U shaped association between BMI and mortality in analyses with a greater potential for bias including all participants, current, former, or ever smokers, and in studies with a short duration of follow-up (<5 years or <10 years), or with moderate study quality scores.

Conclusion Overweight and obesity is associated with increased risk of all cause mortality and the nadir of the curve was observed at BMI 23-24 among never smokers, 22-23 among healthy never smokers, and 20-22 with longer durations of follow-up. The increased risk of mortality observed in underweight people could at least partly be caused by residual confounding from prediagnostic disease. Lack of exclusion of ever smokers, people with prevalent and preclinical disease, and early follow-up could bias the results towards a more U shaped association.

Footnotes

  • We authors thank Darren C Greenwood (Biostatistics Unit, Centre for Epidemiology and Biostatistics, University of Leeds, Leeds) for the Stata code for the non-linear dose-response analysis, and Anders Engeland (Department of Global Public Health, University of Bergen) for clarification of the studies included in the Norwegian Health Survey study.

  • Contributors: DA, TN, and LJV conceived and designed the study. All authors acquired, analysed, or interpreted data and critically revised the manuscript for important intellectual content. MP checked the data extraction. DA did the statistical analysis and drafted the manuscript. DA and LJV obtained funding. LJV supervised the study. DA had full access to all of the data and takes responsibility for the integrity of the data and the accuracy of the data analysis. DA and AS are guarantors.

  • Funding: This project was funded by the liaison committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU), and Imperial College National Institute of Health Research (NIHR) Biomedical Research Centre (BRC). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisation that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been disclosed.

  • Data sharing: No additional data available.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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