LAUSR

Abstract Cigarette smoking is associated with thicker carotid intima-media thickness (IMT), probably partly through inflammatory pathways. However, to what extent does inflammation mediate the smoking-carotid atherosclerosis association is unclear. We investigated the mediating effect of inflammation on the association between cigarette smoking and carotid IMT, and quantified the respective contributions of inflammatory markers to this association. A total of 1752 participants from Guangzhou Biobank Cohort Study-Cardiovascular Disease Sub-cohort (GBCS-CVD) were included. Using causal mediation analysis under the counterfactual framework, we decomposed total effects of cigarette smoking on IMT into indirect effects (through inflammatory response) and direct effects (not through inflammatory response). After adjusting for traditional risk factors, the indirect effects of per 109/L increment in leukocyte and granulocyte, per mg/L increment in high-sensitivity C-reactive protein (hs-CRP), and per mg/dL increment in fibrinogen on carotid IMT was 0.0028 mm (95% confidence interval [CI], 0.0011–0.0047), 0.0019 mm (95% CI, 0.0006–0.0034), 0.0017 mm (95% CI, 0.0006–0.003), and 0.001 mm (95% CI, 0.0001–0.0021), respectively. No evidence for a mediating role of lymphocyte was found. The proportion of the smoking-IMT association mediated by leukocyte, granulocyte, hs-CRP, and fibrinogen was 12.57% (95% CI, 8.50%–22.11%), 8.50% (95% CI, 5.76%–15.09%), 7.64% (95% CI, 5.20%–13.79%), and 4.48% (95% CI, 3.04%–8.03%), respectively. Restricting data analysis to men showed similar results. The effects of cigarette smoking on IMT were partly mediated by leukocyte, hs-CRP, and fibrinogen. The mediating role of leukocyte was likely mainly driven by higher granulocyte.