Title: Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents
Abstract: <h2>Summary</h2><h3>Background</h3> 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. <h3>Methods</h3> 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<sup>2</sup>. <h3>Findings</h3> All-cause mortality was minimal at 20·0–25·0 kg/m<sup>2</sup> (HR 1·00, 95% CI 0·98–1·02 for BMI 20·0–<22·5 kg/m<sup>2</sup>; 1·00, 0·99–1·01 for BMI 22·5–<25·0 kg/m<sup>2</sup>), and increased significantly both just below this range (1·13, 1·09–1·17 for BMI 18·5–<20·0 kg/m<sup>2</sup>; 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<sup>2</sup>; 1·20, 1·18–1·22 for BMI 27·5–<30·0 kg/m<sup>2</sup>). The HR for obesity grade 1 (BMI 30·0–<35·0 kg/m<sup>2</sup>) was 1·45, 95% CI 1·41–1·48; the HR for obesity grade 2 (35·0–<40·0 kg/m<sup>2</sup>) was 1·94, 1·87–2·01; and the HR for obesity grade 3 (40·0–<60·0 kg/m<sup>2</sup>) was 2·76, 2·60–2·92. For BMI over 25·0 kg/m<sup>2</sup>, mortality increased approximately log-linearly with BMI; the HR per 5 kg/m<sup>2</sup> 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<sup>2</sup> units higher BMI (for BMI over 25 kg/m<sup>2</sup>) was greater in younger than older people (1·52, 95% CI 1·47–1·56, for BMI measured at 35–49 years <i>vs</i> 1·21, 1·17–1·25, for BMI measured at 70–89 years; p<sub>heterogeneity</sub><0·0001), greater in men than women (1·51, 1·46–1·56, <i>vs</i> 1·30, 1·26–1·33; p<sub>heterogeneity</sub><0·0001), but similar in studies with self-reported and measured BMI. <h3>Interpretation</h3> 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. <h3>Funding</h3> UK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health.