The Effects of Reverse Causality and Selective Attrition on the Relationship Between Body Mass Index and Mortality in Postmenopausal Women.

Concerns about reverse causality and selection bias complicate the interpretation of studies of body mass index (BMI, calculated as weight (kg)/height (m)2) and mortality in older adults. The objective of this study was to investigate methodological explanations for the apparent attenuation of obesity-related risks in older adults. We used data from 68,132 participants in the Women's Health Initiative (WHI) clinical trial for this analysis. All of the participants were postmenopausal women aged 50-79 years at baseline (1993-1998). To examine reverse causality and selective attrition, we compared rate ratios from inverse probability of treatment- and censoring-weighted Poisson marginal structural models with results from an unweighted adjusted Poisson regression model. The estimated mortality rate ratios and 95% confidence intervals for BMIs of 30.0-34.9, 35.0-39.9 and ≥40.0 were 0.86 (95% confidence interval (CI): 0.77, 0.96), 0.85 (95% CI: 0.72, 0.99), and 0.88 (95% CI: 0.72, 1.07), respectively, in the unweighted model. The corresponding mortality rate ratios were 0.96 (95% CI: 0.86, 1.07), 1.12 (95% CI: 0.97, 1.29), and 1.31 95% CI: (1.08, 1.57), respectively, in the marginal structural model. Results from the inverse probability of treatment- and censoring-weighted marginal structural model were attenuated in low BMI categories and increased in high BMI categories. The results demonstrate the importance of accounting for reverse causality and selective attrition in studies of older adults.