Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents

Emanuele Di Angelantonio, Shilpa N. Bhupathiraju, David Wormser, Pei Gao, Stephen Kaptoge, Amy Berrington de Gonzalez, Benjamin J. Cairns, Rachel Huxley, Chandra L. Jackson, Grace Joshy, Sarah Lewington, Jo Ann E. Manson, Neil Murphy, Alpa V. Patel, Jonathan M. Samet, Mark Woodward, Wei Zheng, Maigen Zhou, Narinder Bansal, Aurelio BarricarteBrian Carter, James R Cerhan, Rory Collins, George Davey Smith, Xianghua Fang, Oscar H. Franco, Jane Green, Jim Halsey, Janet S. Hildebrand, Keum Ji Jung, Rosemary J. Korda, Dale F. McLerran, Steven C. Moore, Linda M. O'Keeffe, Ellie Paige, Anna Ramond, Gillian K. Reeves, Betsy Rolland, Carlotta Sacerdote, Naveed Sattar, Eleni Sofi Anopoulou, June Stevens, Michael Thun, Hirotsugu Ueshima, Ling Yang, Young Duk Yun, Peter Willeit, Emily Banks, Valerie Beral, Zhengming Chen, Susan M. Gapstur, Marc J. Gunter, Patricia Hartge, Sun Ha Jee, Tai Hing Lam, Richard Peto, John D. Potter, Walter C. Willett, Simon G. Thompson, John Danesh, Frank B. Hu

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Abstract

Background Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up. Methods Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4–14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5–<25·0 kg/m 2 . Findings All-cause mortality was minimal at 20·0–25·0 kg/m 2 (HR 1·00, 95% CI 0·98–1·02 for BMI 20·0–<22·5 kg/m 2 ; 1·00, 0·99–1·01 for BMI 22·5–<25·0 kg/m 2 ), and increased significantly both just below this range (1·13, 1·09–1·17 for BMI 18·5–<20·0 kg/m 2 ; 1·51, 1·43–1·59 for BMI 15·0–<18·5) and throughout the overweight range (1·07, 1·07–1·08 for BMI 25·0–<27·5 kg/m 2 ; 1·20, 1·18–1·22 for BMI 27·5–<30·0 kg/m 2 ). The HR for obesity grade 1 (BMI 30·0–<35·0 kg/m 2 ) was 1·45, 95% CI 1·41–1·48; the HR for obesity grade 2 (35·0–<40·0 kg/m 2 ) was 1·94, 1·87–2·01; and the HR for obesity grade 3 (40·0–<60·0 kg/m 2 ) was 2·76, 2·60–2·92. For BMI over 25·0 kg/m 2 , mortality increased approximately log-linearly with BMI; the HR per 5 kg/m 2 units higher BMI was 1·39 (1·34–1·43) in Europe, 1·29 (1·26–1·32) in North America, 1·39 (1·34–1·44) in east Asia, and 1·31 (1·27–1·35) in Australia and New Zealand. This HR per 5 kg/m 2 units higher BMI (for BMI over 25 kg/m 2 ) was greater in younger than older people (1·52, 95% CI 1·47–1·56, for BMI measured at 35–49 years vs 1·21, 1·17–1·25, for BMI measured at 70–89 years; p heterogeneity <0·0001), greater in men than women (1·51, 1·46–1·56, vs 1·30, 1·26–1·33; p heterogeneity <0·0001), but similar in studies with self-reported and measured BMI. Interpretation The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations. Funding UK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health.

Original languageEnglish (US)
Pages (from-to)776-786
Number of pages11
JournalThe Lancet
Volume388
Issue number10046
DOIs
StatePublished - Aug 20 2016

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  • Medicine(all)

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Di Angelantonio, E., Bhupathiraju, S. N., Wormser, D., Gao, P., Kaptoge, S., de Gonzalez, A. B., Cairns, B. J., Huxley, R., Jackson, C. L., Joshy, G., Lewington, S., Manson, J. A. E., Murphy, N., Patel, A. V., Samet, J. M., Woodward, M., Zheng, W., Zhou, M., Bansal, N., ... Hu, F. B. (2016). Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. The Lancet, 388(10046), 776-786. https://doi.org/10.1016/S0140-6736(16)30175-1