Smoking is Associated with Increased Risk of Major Bleeding: A Prospective Cohort Study

Tobacco smoking represents the most preventable cause of several fatal and disabling diseases worldwide. Several ingredients in tobacco have been suspected to cause changes in the arterial wall leading to instability of blood vessels. The association of smoking with major bleeding is largely unexplored. We tested the hypothesis that smoking and high tobacco consumption are associated with increased risk of bleeding.

This is a prospective cohort study with a mean follow-up of 5.9 years including 99,359 individuals from the Copenhagen General Population Study, with a questionnaire including self-reported smoking status and information on smoking intensity in cigarettes per day and pack-years. In this study, 17,555 were current smokers, 40,182 former smokers and 41,622 were never smokers.

Multivariable adjusted hazard ratios for current smokers versus never smokers were 1.49 (95% confidence interval [CI]: 1.38-1.61) for any major bleeding, 1.71 (1.37-2.13) for intracranial bleeding, 1.35 (1.14-1.60) for airway bleeding, 2.20 (1.84-2.62) for gastrointestinal bleeding and 1.39 (1.26-1.55) for urinary bleeding. Increased smoking intensity was also associated with increased risk of any major bleeding, where > 40 pack-years in current and former smokers compared with never smokers had a multivariable adjusted hazard ratio of 1.59 (95% CI: 1.45-1.73) (p for trend across four groups: < 0.001). Also, current smokers smoking > 20 cigarettes per day compared with former and never smokers had a corresponding hazard ratio of 1.67 (1.51-1.85) (p for trend across four groups: < 0.001).

Current smokers have an increased risk of any major bleeding as well as of intracranial, airway, gastrointestinal and urinary bleeding. Also, increased smoking intensity was associated with increased risk of major bleeding.