Accounting for Time-varying Confounding in the Relation between Obesity and Coronary Heart Disease: Analysis with G-estimation, the Atherosclerosis Risk in Communities (ARIC) study

Abstract

In longitudinal studies, standard analysis may yield biased estimates of exposure effect in the presence of time-varying confounders that are also intermediate variables. We aimed to quantify the relationship between obesity and coronary heart disease (CHD) by appropriately adjusting for time-varying confounders. This study performed on a subset of the Atherosclerosis Risk in Communities Study (1987-2010). General obesity defined as body mass index ≥30 kg/m², abdominal obesity (AOB) defined as waist circumference ≥102 cm in men and ≥88 cm in women, and waist to hip ratio categorized at ≥0.9 in men and ≥0.85 in women. The effect of obesity on CHD was estimated by G-estimation and compared with accelerated failure time models using three specifications. The first model adjusted for baseline covariates excluding metabolic mediators of obesity showed increased risk of CHD for all measures of obesity. Further adjustment for metabolic mediators in the second model and time-varying variables in the third model showed negligible hazard ratios. The hazard ratios estimated by G-estimation were 1.15 (95%CI: 0.83-1.47) for General obesity, 1.65 (95%CI: 1.35-1.92) and 1.38 (95%CI: 1.13-1.99) for AOB based on waist circumference and waist to hip ratio, respectively, suggesting that AOB increased the risk of CHD. The G-estimated hazard ratio of both measures was further from the null than standard models.