Refining the association between body mass index and atrial fibrillation: G-formula and restricted mean survival times

Abstract

Background-—Previous studies assessing the association between body mass index (BMI) and atrial fibrillation (AF) did not account for time-varying covariates, which may be affected by previous BMI. We illustrate how the g-formula can account for time-varying confounding. Methods and Results-—We included 4392 participants from the Framingham Heart Study who were AF free at ages 45 to 55 years, and followed them for up to 20 years. We estimated hazard ratios (HRs) comparing time-varying nonobese versus obese with Cox models. We used the g-formula to compare nonobese versus obese and 10% annual decrease in BMI (until normal weight is reached) versus natural course. We estimated HRs and differences in restricted mean survival times, the mean difference in time alive and AF free. We adjusted for sex, age, and time-varying risk factors. Cox models indicated that nonobese participants had a decreased rate of AF versus obese participants (HR, 0.83; 95% CI, 0.72–0.97). G-formula analyses comparing everyone had they been nonobese versus obese yielded stronger associations (HR, 0.73; 95% CI, 0.58–0.91). The restricted mean survival time was 19.22 years had everyone been nonobese and 19.03 years had everyone been obese (difference, 2.25 months; 95% CI, 0.66 to 5.16). When assessing a 10% annual decrease in BMI, the association was weaker (HR 0.96; 95% CI, 0.86–1.08). Conclusions-—Decreased BMI was associated with a lower rate of AF after accounting for time-varying covariates that depend on previous exposure using the g-formula, which Cox models cannot accommodate. Absolute measures like the restricted mean survival time difference offer context to relative measures of association.