Does weight mediate the effect of smoking on coronary heart disease? Parametric mediational g-formula analysis

BACKGROUND: In settings in which there are time-varying confounders affected by previous exposure and a time-varying mediator, natural direct and indirect effects cannot generally be estimated unbiasedly. In the present study, we estimate interventional direct effect and interventional indirect effect of cigarette smoking as a time-varying exposure on coronary heart disease while considering body weight as a time-varying mediator. METHODS: To address this problem, the parametric mediational g-formula was proposed to estimate interventional direct effect and interventional indirect effect. We used data from the Multi-Ethnic Study of Atherosclerosis to estimate effect of cigarette smoking on coronary heart disease, considering body weight as time-varying mediator. RESULTS: Over a 11-years period, smoking 20 cigarettes per day compared to no smoking directly (not through weight) increased risk of coronary heart disease by an absolute difference of 1.91% (95% CI: 0.49%, 4.14%), and indirectly decreased coronary heart disease risk by -0.02% (95% CI: -0.05%, 0.04%) via change in weight. The total effect was estimated as an absolute 1.89% increase (95% CI: 0.49%, 4.13%). CONCLUSION: The overall absolute impact of smoking to incident coronary heart disease is modest, and we did not discern any important contribution to this effect relayed through changes to bodyweight. In fact, changes in weight because of smoking have no meaningful mediating effect on CHD risk.