Estimating the Time-Varying Joint Effects of Obesity and Smoking on All-Cause Mortality Using Marginal Structural Models

Obesity and smoking are independently associated with a higher mortality risk, but previous studies have reported conflicting results about the relationship between these 2 time-varying exposures. Using prospective longitudinal data (1987-2007) from the Atherosclerosis Risk in Communities Study, our objective in the present study was to estimate the joint effects of obesity and smoking on all-cause mortality and investigate whether there were additive or multiplicative interactions. We fit a joint marginal structural Poisson model to account for time-varying confounding affected by prior exposure to obesity and smoking. The incidence rate ratios from the joint model were 2.00 (95% confidence interval (CI): 1.79, 2.24) for the effect of smoking on mortality among nonobese persons, 1.31 (95% CI: 1.13, 1.51) for the effect of obesity on mortality among nonsmokers, and 1.97 (95% CI: 1.73, 2.22) for the joint effect of smoking and obesity on mortality. The negative product term from the exponential model revealed a submultiplicative interaction between obesity and smoking (beta = -0.28, 95% CI: -0.45, -0.11; P < 0.001). The relative excess risk of interaction was -0.34 (95% CI: -0.60, -0.07), indicating the presence of subadditive interaction. These results provide important information for epidemiologists, clinicians, and public health practitioners about the harmful impact of smoking and obesity.