Biomarkers of Endothelial Activation in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study

Background: Endothelial cell activation seems to be an important process in the multifactorial pathophysiology of delayed cerebral ischemia (DCI) and subsequent poor clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Aim: To assess the association between biomarker levels of endothelial activation and the occurrence of DCI and poor clinical outcome six months after aSAH. Methods: Between October 2018 and November 2020, 75 aSAH patients were included. Blood samples were taken on admission, days 3-5 and days 9-11 after aSAH. Ten patients with unruptured intracranial aneurysms served as controls. Poor outcome was assessed at six months, defined by a modified Rankin Scale score of 4-6. The cohort was dichotomized into patients with and without DCI and good and poor outcomes. Biomarker levels of von Willebrand factor (vWF), E-selectin, thrombomodulin, syndecan-1 and matrix metalloproteinase (MMP-9) were analyzed and compared between groups by a T-test or Mann-Whitney U test, depending on the normality of the data. Results: Twelve (16.0%) patients developed DCI, and 39 (41.9%) patients had poor outcomes at six months post-aSAH. None of the biomarkers showed significant differences between patients with and without DCI. vWF and syndecan-1 were elevated on admission and on days 9-11 in patients with poor outcomes (p < 0.05 and p = 0.02, respectively). Conclusion: Levels of vWF, E-selectin, thrombomodulin, syndecan-1 and MMP-9 were not associated with the occurrence of DCI, although higher levels of vWF and syndecan-1 were associated with poor outcome at six months. Further research is needed to establish the role of these biomarkers in aSAH patients.