The Causes and Natural History of Intracranial Aneurysms : A Future Role for Statins?

Kataoka Hiroharu

doi:10.7887/jcns.23.702

The natural history of unruptured intracranial aneurysms (uIAs) in Japan was revealed by the SUAVe study and UCAS Japan. The SUAVe study was a prospective study in which small uIAs (less than 5 mm in diameter) were observed without treatment. In the SUAVe study, the average annual rupture rate of small uIAs was 0.54% per year. UCAS Japan was a prospective cohort study of newly diagnosed uIAs in which 6,697 uIAs were enrolled. In UCAS Japan, the average annual rupture rate was 0.95% per year, and the risk factors for rupture were size, location and bleb formation. In comparison with the ISUIA cohort which consists of North Americans, the rupture rate of uIAs of equal size was higher in Japanese. Posterior communication artery aneurysms were prone to rupture in both cohorts, but anterior communicating artery aneurysms showed a higher risk of rupture only in the Japanese cohort. A wide variety of evidence supports the notion that IA formation is closely associated with inflammation. Hemodynamic stress provokes inflammatory reactions in endothelial cells including the activation of nuclear factor-kappa B (NF-κB), which causes the recruitment of macrophages into IA walls. Macrophages secrete matrix metalloproteinases (MMPs)-2 and -9 that promote IA wall degradations. Treatment with statins suppressed the progression of rat IAs by inhibiting inflammatory reactions. A multi-center prospective randomized trial examining the inhibitory effect of statins on the progression and rupture of human IAs, Small Unruptured Aneurysm Verification-Prevention Effect against Growth of cerebral Aneurysm Study Using Statin (SUAVe-PEGASUS) study is now ongoing.

The Causes and Natural History of Intracranial Aneurysms : A Future Role for Statins?

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