Weight History and All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies

Background: The relationship between body mass index (BMI) and mortality is controversial. Objective: To investigate the relationship between maximum BMI over 16 years and subsequent mortality. Design: 3 prospective cohort studies. Setting: Nurses' Health Study I and II and Health Professionals Follow-Up Study. Participants: 225 072 men and women with 32 571 deaths observed over a mean of 12.3 years of follow-up. Measurements: Maximum BMI over 16 years of weight history and all-cause and cause-specific mortality. Results: Maximum BMIs in the overweight (25.0 to 29.9 kg/m(2)) (multivariate hazard ratio [HR], 1.06 [95% CI, 1.03 to 1.08]), obese I (30.0 to 34.9 kg/m(2)) (HR, 1.24 [CI, 1.20 to 1.29]), and obese II (>= 35.0 kg/m(2)) (HR, 1.73 [CI, 1.66 to 1.80]) categories were associated with increases in risk for all-cause death. The pattern of excess risk with a maximum BMI above normal weight was maintained across strata defined by smoking status, sex, and age, but the excess was greatest among those younger than 70 years and never-smokers. In contrast, a significant inverse association between overweight and mortality (HR, 0.96 [CI, 0.94 to 0.99]) was observed when BMI was defined using a single baseline measurement. Maximum overweight was also associated with increased cause-specific mortality, including death from cardiovascular disease and coronary heart disease. Limitation: Residual confounding and misclassification. Conclusion: The paradoxical association between overweight and mortality is reversed in analyses incorporating weight history. Maximum BMI may be a useful metric to minimize reverse causation bias associated with a single baseline BMI assessment.