Background The main associations of body-mass index (BMI) with overall and cause-specific mortality can best be assessed by long-term prospective follow-up of large numbers of people. The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies. Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with 894 576 participants, mostly in western Europe and North America (61% [n=541 452] male, mean recruitment age 46 [SD 11] years, median recruitment year 1979 [IQR 1975-85], mean BMI 25 [SD 4] kg/m2). The analyses were adjusted for age, sex, smoking status, and study. To limit reverse causality, the first 5 years of follow-up were excluded, leaving 66 552 deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): 30 416 vascular; 2070 diabetic, renal or hepatic; 22 592 neoplastic; 3770 respiratory; 7704 other. Findings In both sexes, mortality was lowest at about 22·5-25 kg/m2. Above this range, positive associations were recorded for several specific causes and inverse associations for none, the absolute excess risks for higher BMI and smoking were roughly additive, and each 5 kg/m2 higher BMI was on average associated with about 30% higher overall mortality (hazard ratio per 5 kg/m2 [HR] 1·29 [95% CI 1·27-1·32]): 40% for vascular mortality (HR 1·41 [1·37-1·45]); 60-120% for diabetic, renal, and hepatic mortality (HRs 2·16 [1·89-2·46], 1·59 [1·27-1·99], and 1·82 [1·59-2·09], respectively); 10% for neoplastic mortality (HR 1·10 [1·06-1·15]); and 20% for respiratory and for all other mortality (HRs 1·20 [1·07-1·34] and 1·20 [1·16-1·25], respectively). Below the range 22·5-25 kg/m2, BMI was associated inversely with overall mortality, mainly because of strong inverse associations with respiratory disease and lung cancer. These inverse associations were much stronger for smokers than for non-smokers, despite cigarette consumption per smoker varying little with BMI. Interpretation Although other anthropometric measures (eg, waist circumference, waist-to-hip ratio) could well add extra information to BMI, and BMI to them, BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5-25 kg/m2. The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal. At 30-35 kg/m2, median survival is reduced by 2-4 years; at 40-45 kg/m2, it is reduced by 8-10 years (which is comparable with the effects of smoking). The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases, and is not fully explained.
Bibliographical noteFunding Information:
All the writing committee (except NQ) work in the CTSU, which has a policy of staff not accepting fees, honoraria, or consultancies. The CTSU is involved in clinical trials with funding from the UK Medical Research Council, British Heart Foundation, and/or various companies (AstraZeneca, Bayer, Merck, Schering-Plough, Solvay) as research grants to (and administered by) the University of Oxford. NQ is a former Director of Epidemiology at GlaxoSmithKline and now works in Oxon Epidemiology, which has undertaken consultancy work for several pharmaceutical companies (including GlaxoSmithKline, Pfizer, Lilly, Roche, Gilead, and Grunenthal).
The Prospective Studies Collaboration has been supported by the UK Medical Research Council, British Heart Foundation, Cancer Research UK, EU BIOMED programme, NIA grant P01 AG17625-01, and CTSU overheads. Merck (F Walker) helped support the 1996 meeting of collaborators. Gary Whitlock was supported by a Girdlers' Health Research Council of New Zealand Fellowship. Sarah Lewington had a British Heart Foundation Fellowship to coordinate the project. Sarah Parish supplied unpublished analyses of BMI and cotinine ( webappendix ).