Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration–Tobacco Working Group

BACKGROUND: Understanding the association of tobacco product use with subclinical markers is essential in evaluating health effects to inform regulatory policy. This is particularly relevant for noncigarette products (eg, cigars, pipes, and smokeless tobacco), which have been understudied because of their low prevalence in individual cohort studies. METHODS: This cross-sectional study included 98 450 participants from the Cross-Cohort Collaboration–Tobacco data set. Associations between the use of tobacco products and subclinical markers (high-sensitivity C-reactive protein, interleukin-6, fibrinogen, D-dimer, coronary artery calcium, carotid intima-media thickness, carotid plaque, and ankle-brachial index) were evaluated. The analyses used multivariable linear and logistic regression models to examine current use status for each product, with additional analyses of “sole” and “exclusive” noncigarette use (versus never use of either cigarettes or a specific noncigarette tobacco). Sole use was defined as the current use of a given noncigarette tobacco without concurrent combustible cigarette use, whereas exclusive use was defined as current noncigarette tobacco use without any history of combustible cigarette use. RESULTS: A total of 20.0%, 3.0%, 0.8%, and 1.5% of participants were current cigarette, cigar, pipe, or smokeless tobacco users, respectively. Current cigarette use showed associations with higher levels of all markers compared with never cigarette use. Compared with the relevant reference group, current, sole, and exclusive cigar use was associated with 10% (95% CI, 1–20), 19% (95% CI, 12–26), and 11% (95% CI, 2–21) higher high-sensitivity C-reactive protein on the geometric mean scale. Similar associations were observed for pipe and smokeless tobacco use. For interleukin-6, we observed that sole cigar use was associated with a 15% (95% CI, 6–24) higher geometric mean level, whereas current, sole, and exclusive pipe use were associated with 22% to 32% (all P values <0.05) higher levels compared with their respective reference groups. Fibrinogen levels were 2% to 6% higher (all P values <0.05) among current users of cigars, pipes, and smokeless tobacco compared with their respective reference groups. Carotid plaque and carotid intima-media thickness were also moderately associated with noncigarette tobacco use. CONCLUSIONS: Use of noncigarette tobacco products is linked to subclinical markers relevant to cardiovascular harm. Inflammatory markers, such as high-sensitivity C-reactive protein and interleukin-6, have the potential for assessing early cardiovascular risk from these products and aiding regulatory authorities in evaluating their associated risks.