Abstract DP321: Serum Alpha-1 Antitrypsin Levels in Ruptured and Unruptured Cerebral Aneurysms: A Prospective Study

Introduction: Alpha-1 antitrypsin (AAT) is a potent anti-protease that plays an important role in maintaining the integrity of arterial walls, and its severe deficiency has been reported in patients with 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. In this study, we tested the hypothesis that serum AAT levels differ between patients with ruptured and unruptured aneurysms. The primary goal of this pilot study is to introduce the concept of measuring serum AAT as a potential biomarker for vessel wall instability in cerebral aneurysms. Methods: We conducted a prospective study of consecutive patients at an academic center from May 2024 through June 2025. After obtaining informed consent, 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 without cerebral aneurysms who served as a control group. We compared serum AAT levels among groups using ANOVA. We then assessed the association between serum AAT levels and aneurysm status (ruptured vs. unruptured) using multivariable logistic regression analysis. Results: Of 78 enrolled patients, we included 75 with complete data (mean age 60 years old SD 15.4, 65% female) of whom 41 had ruptured aneurysms, 14 had unruptured aneurysms with no prior history of rupture and 20 were in the control group with acute stroke but no cerebral aneurysm on vascular imaging. Serum AAT levels were higher in patients with ruptured aneurysms (mean 194 md/dl SD 45.4) compared to unruptured (mean 153 md/dl SD 21.6) and no aneurysm groups (mean 162.4 md/dl SD 30.8). (p<0.001, Figure ) Higher serum AAT levels were associated with ruptured aneurysm status (OR 1.02 for 1mg/dl increase in serum level, 95% CI 1.01-1.04; p=0.017) independent of patient age, AAT phenotype and serum CRP levels. There was no association between AAT levels and the size or number of aneurysms. Conclusion: 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 processes. Future studies are needed to explore the potential use of AAT as a biomarker for arterial wall instability and rupture risk in cerebral aneurysms.