The mediating role of the venules between smoking and ischemic stroke

Figures

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  Fig. 1. Flow diagram of the study. *Retinal images of 805 persons of the total 2506 participants were randomly selected for retinal caliber measurement

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  Fig. 2. A drawing showing the four-way decomposition of the total effect of smoking (A) on incident stroke (Y) via wider venules (M). Interaction of smoking with wider venules is reflected by A*M. Arrow 1 reflects the Controlled Direct Effect [CDE], effect of smoking (exposure) on stroke (outcome) independent of wider venules (mediator); Arrow 2 reflects the pure indirect effect [PIE], the effect of smoking solely through wider venules without any interaction; Arrow 3 reflects reference interaction [INT(ref)], the interaction between smoking and wider venules without smoking having an effect on wider venules; Arrow 4 reflects mediated interaction [INT(med)], interaction between smoking and that component of wider venules, which is due to the effect of smoking

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  Fig. 3. A causal diagram in which C confounds the smoking/ischemic stroke, wider venules/ischemic stroke, and smoking/wider venules relation. We assume there is no unmeasured confounding, and that smoking does not affect C. Here C and U refer to the following list of measured person characteristics: age, sex, subcohort, education, systolic blood pressure, diastolic blood pressure, blood pressure lowering medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, white blood cell counts, diabetes mellitus, alcohol intake, carotid plaques, history of cardiovascular disease, and retinal arteriolar caliber

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  Fig. 4. Illustrates how a crude natural direct effect estimate of 1.48 and a crude natural indirect effect estimate of 1.05 (the intercept on y-axis) would change under different magnitudes of confounding by a binary unmeasured variable U. The difference between the observed effect and bias-corrected-effect is depicted on the Y-axis, and the difference in prevalence of U between non-smokers and smokers is depicted on the X-axis. The colored lines are a range of plausible values for the effect of U on ischemic stroke. (Color figure online)