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CORESTA Congress, Edinburgh, 2010, SS 04; TSRC, Tob. Sci. Res. Conf., 2010, 64, abstr. 36

Cardiovascular disease biomarkers study, Part III: Tobacco-related biomarkers of effect in exclusive cigarette smokers, exclusive moist snuff consumers, and non-consumers of tobacco

NORDSKOG B.K.; BROWN B.G.; JONES B.A.; HEAVNER D.L.; STEICHEN T.J.; BORGERDING M.F.
R.J. Reynolds Tobacco Company, R&D, Winston-Salem, NC, USA

A three cohort, age-stratified cross-sectional study was conducted in the U.S. in cigarette smokers (n=60), moist snuff consumers (n=48) and non-consumers of tobacco (n=60) to evaluate several known cardiovascular biomarkers of effect. Subject enrolment was restricted to generally healthy males (26-49 years) who were free of clinically significant health problems, not taking medication for chronic medical disorders, willing to undergo all study procedures including one overnight confinement, tested negative for drugs and alcohol, and measured =70% of predicted for FEV1 on spirometry. Physiological assessments included measures of flow mediated dilation (FMD), ankle-brachial index (ABI) and expired CO (ECO) on Days 1 and 2; carotid intima-media thickness (CIMT) and spirometry on Day 2. Forty-five blood biomarkers of tobacco exposure/effect and fourteen clinical hematology indices were also evaluated. For the cardiovascular-related physiological assessments, no significant differences were found between cohorts for FMD or CIMT although a significant age group main effect was observed for CIMT. Smokers had a lower mean ABI value following normal smoking behavior, but this difference was lost after a 10-12 hour overnight tobacco-abstinence period. ECO was significantly different between the cohort that smoked and the two that did not. Approximately half (n=22) of the measured blood biomarkers of effect showed differences in cohort comparisons. IL-12(p70), ICAM1, IL8 and MCP1 were the biomarkers that best differentiated the three cohorts. Age effects were also seen. In conclusion, significant cohort and age effect differences were identified. Concentrations of measured biomarkers were consistent with normal clinical ranges; however, differences between cohorts (within normal ranges) were observed.