The effect of reverse causality and selective attrition on the relationship between body mass index and mortality in postmenopausal women

Abstract

Concerns about reverse causality and selection bias complicate the interpretation of studies of body mass index (BMI) and mortality in older adults. The objective of this manuscript is to investigate methodological explanations for the apparent attenuation of obesity-related risks in older adults. We used data from 68,132 participants from the Women’s Health Initiative (WHI) clinical trial in this analysis. All of the participants were postmenopausal women aged 50-79 at baseline (1993-1998). To examine reverse causality and selective attrition, we compared rate ratios from inverse probability of treatment (IPTW) and censoring (IPCW) weighted Poisson marginal structural models to results from an unweighted adjusted Poisson regression model. The estimated mortality rate ratios and 95% confidence intervals for BMI 30-34.9, 35-39.9 and >40 kg/m2 were 0.86 (0.77, 5.48), 0.85 (0.72, 0.99), and 0.88 (0.72, 1.07) in the unweighted model. The corresponding mortality rate ratios were 0.96 (0.86, 1.07), 1.12 (0.97, 1.29), and 1.31 (1.08, 1.57) in the marginal structural model. Results from the IPTW and IPCW 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.