Plasma Fibulin-5 Levels as an Independent Predictor of a Poor Outcome after an Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is a poor-outcome disease with a delayed neurological exacerbation. Fibulin-5 (FBLN5) is one of matricellular proteins, some of which have been involved in SAH pathologies. However, no study has investigated FBLN5's roles in SAH. This study was aimed at examining the relationships between serially measured plasma FBLN5 levels and neurovascular events or outcomes in 204 consecutive aneurysmal SAH patients, including 77 patients (37.7%) with poor outcomes (90-day modified Rankin Scale 3-6). Plasma FBLN5 levels were not related to angiographic vasospasm, delayed cerebral ischemia, and delayed cerebral infarction, but elevated levels were associated with severe admission clinical grades, any neurological exacerbation and poor outcomes. Receiver-operating characteristic curves indicated that the most reasonable cut-off values of plasma FBLN5, in order to differentiate 90-day poor from good outcomes, were obtained from analyses at days 4-6 for all patients (487.2 ng/mL; specificity, 61.4%; and sensitivity, 62.3%) and from analyses at days 7-9 for only non-severe patient (476.8 ng/mL; specificity, 66.0%; and sensitivity, 77.8%). Multivariate analyses revealed that the plasma FBLN5 levels were independent determinants of the 90-day poor outcomes in both all patients' and non-severe patients' analyses. These findings suggest that the delayed elevation of plasma FBLN5 is related to poor outcomes, and that FBLN5 may be a new molecular target to reveal a post-SAH pathophysiology.