Cigarette Smoking and Observed Growth of Unruptured Intracranial Aneurysms: A Systematic Literature Review and Meta-Analysis

BACKGROUND: Smoking and observed growth of intracranial aneurysms are known risk factors for rupture. The mechanism by which smoking increases this risk is not completely elucidated. Furthermore, an association between smoking and aneurysm growth has not been clearly defined in the literature. We hypothesize that smoking is associated with aneurysm growth, which, in turn, may serve as one of the mechanisms by which smoking drives rupture risk. METHODS: We report a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Using the R software, we performed a meta-analysis to investigate the association between smoking and the growth of unruptured intracranial aneurysms. Studies on familial aneurysms and genetic syndromes known to increase the risk of aneurysms were excluded. RESULTS: Eighteen observational studies were included with a total of 3535 patients and 4289 aneurysms with a mean follow-up period ranging from 17 to 226 months. The mean age among the studies ranged from 38.4 to 73.9 years; 74% of patients were female. Ever-smoking status (odds ratio, 1.10 [95% CI, 0.87–1.38]) and current smoking status (odds ratio, 1.43 [95% CI, 0.84–2.43]) did not show a statistically significant association with growth of intracranial aneurysms. Patients currently smoking did not have a statistically significant association with the growth of intracranial aneurysms (odds ratio, 1.18 [95% CI, 0.72–1.93]) compared with patients without a smoking history. No significant association was found in patients who previously smoked compared with patients who never smoked (odds ratio, 1.46 [95% CI, 0.88–2.43]). CONCLUSIONS: Smoking is not clearly associated with the growth of unruptured intracranial aneurysms, despite trends being observed, there is no statistical association. The mechanism by which smoking increases rupture risk might not be growth. In patients for whom observation is recommended, the absence of growth over time in the setting of smoking history does not, therefore, imply protection from rupture.