Abstract
BACKGROUND: Smoking has been associated with negative cardiovascular health outcomes. We analyzed data from The Population Assessment of Tobacco and Health (PATH) Study to investigate whether certain biomarkers collected were related to both cardiovascular disease (CVD) occurrence and cigarette or e-cigarette use. METHODS: A total of 6,473 participants were grouped into cigarette users, e-cigarette users, and non-users. Among them, 6,020 (93%) developed CVD and 453 (7%) did not over PATH Study Waves 1 to 5. All participants were adults, had valid tobacco use and biomarker data, and no pre-existing CVD prior to Wave 1.We conducted mediation analysis using nonlinear multiple additive regression trees (MART) method to determine if there were biomarkers that mediated, or helped explain, the association between cigarette and e-cigarette use and cardiovascular disease occurrence. A total of 59 biomarkers were analyzed to determine their associations to cardiovascular disease. RESULTS: There was a significant association (p< 0.001) between CVD and cigarette use, with cigarette users having 11% higher odds of CVD than non-users. Biomarkers soluble intercellular adhesion molecule-1 (sICAM-1) and high-sensitivity C-reactive protein (hsCRP) significantly mediated the relationship between cigarette use and CVD with relative indirect effect of 20.7% (95% CI: 4.5% - 45.6%) and 82.7% (95% CI: 51.2% - 100.0%), respectively. Although there were higher odds of CVD, no significant effect was found for exclusive e-cigarette users (p = 0.259). CONCLUSIONS: Inflammatory biomarkers sICAM-1 and hsCRP mediated the association between cigarette use and CVD, suggesting their potential as biomarkers for cardiovascular risk in smokers.