Cotinine Levels Influence the Risk of Rupture of Brain Aneurysms

Abstract The relationship between nicotine levels in smokers and brain aneurysm has never been determined. To assess the levels of cotinine in smoker patients with ruptured and unruptured brain aneurysm and the risk of aneurysm rupture we quantified cotinine levels in smoker patients with ruptured or unruptured brain aneurysms. We identified a control group of smokers and nonsmokers without brain aneurysm. Out of 182 participants cerebral aneurysms were statistically significantly associated with smoking (P<0.001) and female sex (P=0.006). Cotinine levels were significantly correlated with both the presence (P=0.009) and the rupture (P=0.002) of brain aneurysms. Compared with nonsmokers, smokers had a 5-fold higher risk of having a brain aneurysm (OR, 5.72; 95% CI, 2.96–11.07; P<0.001). The risk of rupture of brain aneurysms increased by 50% with each cotinine unit and was 4-fold higher with cotinine levels between 4 and 6 (OR, 3.75; 95% CI, 1.48–9.53; P=0.005). With increasing age, the cotinine level decreased (P <0.001, rho= –0.28), declining by 2% with each year of age. In the whole population, the probability of a ruptured aneurysm in patients with cotinine levels between 4 and 6 was higher than in those with levels between 0 and 3 (OR, 5.55; 95% CI, 1.08–28.5; P=0.040). Our results suggest that high cotinine levels in smokers with brain aneurysm, rather than size, are significantly associated with high rupture risk. Cotinine levels decrease with age, possibly reducing the risk of formation and rupture of a brain aneurysm.