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
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.
British Medical Journal