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Factors Affecting Formation and Growth of Intracranial Aneurysms: A Long-Term Follow-Up Study

Background and Purpose — We sought to investigate factors determining growth rate of unruptured intracranial aneurysms as well as formation of new (de novo) aneurysms in patients from a time period when unruptured aneurysms were not treated surgically. Methods — Eighty-seven patients (79 had ruptured aneurysms clipped at start of follow-up) with 111 unruptured aneurysms as well as an additional 7 patients (2 with and 5 without unruptured aneurysms) who developed new aneurysms were followed from the 1950s to the 1970s until death or subarachnoid hemorrhage or until the last contact. Patients’ cerebral arteries were examined later either with conventional (control) angiography (n=38) and/or, for those alive during 1996–1998, with 3-dimensional CT angiography (n=57). In addition, 10 patients were studied at neuropathological autopsy. Results — Mean±SD duration of follow-up was 18.9±9.4 years (range, 1.2 to 38.9 years). Unruptured aneurysms increased in size ≥1 mm in 39 of the 87 patients (45%) and ≥3 mm in 31 (36%). New aneurysms were found in 15 of the 89 patients and in 5 without an unruptured aneurysm at the beginning of follow-up. Aneurysm rupture was associated very significantly (P <0.001) with aneurysm growth during follow-up. Of several potential risk factors tested, only cigarette smoking (odds ratio [OR], 3.92; 95% CI, 1.29 to 11.93) and female sex (OR, 3.36; 95% CI, 1.11 to 10.22) were, after adjustment for age, significant (P <0.05) independent risk factors for occurrence of aneurysm growth of ≥1 mm. Only cigarette smoking (OR, 3.48; 95% CI, 1.14 to 10.64;P <0.05) was associated with growth of ≥3 mm. Age- and hypertension-adjusted risk factors for aneurysm formation were female sex (OR, 4.73; 95% CI, 1.16 to 19.38) and cigarette smoking (OR, 4.07; 95% CI, 1.09 to 15.15). Conclusions — Women and cigarette smokers are at increased risk for intracranial aneurysm formation and growth. Cigarette smoking in particular hastens aneurysm growth. Cessation of smoking is important for patients with unruptured aneurysms and possibly also for those with a prior subarachnoid hemorrhage.