Natural History of Unruptured Intracranial Aneurysms A Long-term Follow-up Study

Background and Purpose Unruptured intracranial aneurysms are increasingly being detected and are a notable healthcare burden. We investigated the long-term natural history of unruptured intracranial aneurysms and risk factors predictive of subsequent rupture. Methods A total of 142 patients with 181 unruptured intracranial aneurysms diagnosed between 1956 and 1978, when these were not treated, were followed up until death or subarachnoid hemorrhage, or until 2011 to 2012. Annual and cumulative incidences of aneurysm rupture and risk factors for rupture were studied using Kaplan-Meier survival analysis and Cox proportional hazards regression models. Results The median follow-up time was 21.0 (range, 0.8-52.3) years. During 3064 person-years, there were 34 first episodes of aneurysm rupture, giving an average annual incidence of 1.1%. Eighteen patients died on account of an initial or recurrent aneurysm rupture. The cumulative rate of bleeding was 10.5% (95% confidence interval [CI], 5.2-15.8) at 10 years, 23.0% (95% CI, 15.4-30.6) at 20 years, and 30.1% (95% CI, 21.3-38.9) at 30 years. None of the index aneurysms bled after a follow-up of 25 years. Cigarette smoking (adjusted hazard ratio, 2.44; 95% CI, 1.02-5.88), location of the aneurysm in the anterior communicating artery (adjusted hazard ratio, 3.73; 95% CI, 1.23-11.36), patient age inversely (0.96 per year, 95% CI, 0.92-1.00) and aneurysm diameter 7 mm (adjusted hazard ratio, 2.60; 95% CI, 1.13-5.98) independently predicted subsequent aneurysm rupture, as did alcohol consumption (1.27 per 100 g/week; 95% CI, 1.05-1.53; P<0.05), but only in univariable analysis. Conclusions Cigarette smoking, patient age inversely, and the size and location of the unruptured intracranial aneurysm seem to be risk factors for aneurysm rupture. The risk of bleeding decreases with a very long-term follow-up.