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

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.