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 (β = –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.

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