To test the hypothesis that serum Alpha-1 antitrypsin (AAT) levels differ between patients with ruptured and unruptured cerebral aneurysms.

AAT is a potent anti-protease that helps maintain arterial wall integrity, and severe deficiency has been linked to aortic aneurysms. However, it remains unclear whether seemingly normal serum AAT levels, in the absence of severe deficiency, are associated with ruptured or unruptured cerebral aneurysms.

We conducted a prospective study of consecutive patients at an academic center in 2024-2025. We measured serum AAT levels and phenotypes, along with serum C-reactive protein (CRP) to control for acute-phase reactivity, in patients with ruptured and unruptured cerebral aneurysms, as well as in patients with acute stroke without aneurysms who served as control group. We compared serum AAT levels among groups, then tested the association between serum AAT levels and aneurysm rupture status using multivariable logistic regression analysis. 

Of 87 enrolled patients, 84 with complete data were included (mean age 60 years [SD 15.4], 65% female): 44 with ruptured aneurysms, 20 with unruptured aneurysms, and 20 controls. Serum AAT levels were higher in ruptured aneurysms (mean 193 mg/dL [SD 44]) compared to unruptured (154 mg/dL [SD 21]) and control groups (159 mg/dL [SD 32]; p<0.001). Higher serum AAT levels were independently associated with ruptured aneurysms (OR 1.03 per 1 mg/dL increase, 95% CI 1.01–1.05; p=0.02), after adjusting for age, aneurysm size, AAT phenotype, and CRP.

Serum AAT levels appear to be higher in patients with ruptured cerebral aneurysms compared to those with unruptured aneurysms. This may reflect increased AAT activity as a response to arterial wall destructive process. Future studies are needed to explore the potential use of AAT as a biomarker for arterial wall instability and rupture risk in cerebral aneurysms.