Reverse causality and confounding and the associations of overweight and obesity with mortality

Objective: To examine the effect of reverse causality and confounding on the association of BMI with all‐cause and cause‐specific mortality. Research Methods and Procedures: Data from two large prospective studies were used. One (a community‐based cohort) included 8327 women and 7017 men who resided in two Scottish towns at the time of the baseline assessment in 1972–1976; the other (an occupational cohort) included 4016 men working in the central belt of Scotland at the time of the baseline assessment in 1970–1973. Participants in both cohorts were ages 45 to 64 years at baseline; the follow‐up period was 28 to 34 years. Results: In age‐adjusted analyses that did not take account of reverse causality or smoking, there was no association between being overweight (BMI 25 to <30 kg/m²) and mortality, and weak to modest associations between obesity (BMI ≥30 kg/m²) and mortality. There was a strong association between smoking and lower BMI in women and men in both cohorts (all p < 0.0001). Among never‐smokers and with the first 5 years of deaths removed, overweight was associated with an increase in all‐cause mortality (relative risk ranging from 1.12 to 1.38), and obesity was associated with a doubling of risk in men in both cohorts (relative risk, 2.10 and 1.96, respectively) and a 60% increase in women (relative risk, 1.56). In both never‐smokers and current smokers, being overweight or obese was associated with important increases in the risk of cardiovascular disease. Discussion: These findings demonstrate that with appropriate control for smoking and reverse causality, both overweight and obesity are associated with important increases in all‐cause and cause‐specific mortality, and in particular with cardiovascular disease mortality.