Forearm Endothelial Response in Smokeless Tobacco Users Compared with Cigarette Smokers and Nonusers of Tobacco

Mark C. Granberry, Pharm.D., Eugene S. Smith III, M.D., Rhonda D. Troillett, M.S., and John F. Eidt, M.D.


Pharmacotherapy. 2003;23(8) 

In This Article

Abstract and Introduction

Study Objective: To compare brachial artery flow-mediated dilation (FMD) in subjects who use smokeless tobacco, smoke cigarettes, or do not use any tobacco product.
Design: Cross-sectional study.
Setting: University-affiliated outpatient clinic.
Subjects: Seventeen apparently healthy volunteers who for more than 1 year smoked at least 10 cigarettes/day, used at least two containers of smokeless tobacco/week, or did not use any tobacco product.
Measurements and Main Results: Baseline characteristics of subjects were similar among the three groups except for mean age and serum cotinine level. Baseline brachial artery diameter, endothelium-dependent FMD induced by reactive hyperemia, and endothelium-independent dilation induced by administration of sublingual nitroglycerin were measured. Mean FMD over baseline was 4.1% ± 0.7% in subjects who used smokeless tobacco, 3.9% ± 5.1% in cigarettes smokers, and 12.2% ± 5.7% in nonusers of tobacco (p=0.01). Endothelium-independent dilation induced by nitroglycerin was not statistically different among the three groups.
Conclusion: Brachial artery FMD, a surrogate for endothelial dysfunction, was significantly impaired in smokeless tobacco users and cigarette smokers compared with nonusers of tobacco.

Smokeless tobacco use is widespread, especially in the south and southwest regions of the United States, and especially in young men. One report indicated that up to 25% of high school males regularly use smokeless tobacco.[1] Cigarette smoking is well known to increase the risk of cardiovascular disease, but an exact causative mechanism has not been clearly defined.[2,3] It is therefore unclear whether the increase in cardiovascular disease is related to a property that is intrinsic to the tobacco plant, or a compound that results only after the tobacco plant is burned and the smoke is inhaled. If inhalation of the smoke from burned tobacco is not required to increase the risk of cardiovascular disease, then smokeless tobacco potentially has a similar detrimental effect.

Initial reports regarding the effect of smokeless tobacco use on the risk of cardiovascular disease are conflicting. One study of over 6000 smokeless tobacco users in Sweden found that these individuals had a 40% increased risk of death from cardiovascular disease compared with nonusers of tobacco.[4] However, a more recent population-based study, also from Sweden, found that smokeless tobacco use was not associated with increased risk of myocardial infarction.[5] The authors warned against extrapolating their results to individuals in other countries because the smokeless tobacco sold in Sweden is prepared by a different method, and the contents differ significantly from those in the smokeless tobacco sold in the United States and elsewhere.

Although the mechanism by which cigarette smoking increases the risk of cardiovascular disease is probably multifactorial, an important early event in the atherosclerotic process is dysfunction of the vascular endothelium.[6] Studies of cigarette smokers without known vascular disease consistently show that these individuals have impaired endothelial function.[7,8,9] Unlike the well-documented effects that cigarette smoking has on the vascular endothelium, the effect of smokeless tobacco on the endothelium has not been determined. Therefore, we compared the vascular endothelial function in smokeless tobacco users, cigarette smokers, and nonusers of tobacco. Specifically, we compared brachial artery flow-mediated dilation (FMD) in healthy volunteers who were either smokeless tobacco users, cigarette smokers, or nonusers of tobacco.