Plasminogen activator inhibitor-1 4G allele in the 4G/5G promoter polymorphism increases the occurrence of cerebral ischemia after aneurysmal subarachnoid hemorrhage

BACKGROUND AND PURPOSE: In several acute life-threatening diseases, the 4G-allele in the 4G/5G-promotor polymorphism in the plasminogen activator inhibitor-1 (PAI-1) gene is associated with higher PAI-1 levels and increased poor outcome, probably by promoting the formation of microthrombi. The aim of the present study was to investigate whether the PAI-1 4G/5G polymorphism is associated with the occurrence of cerebral ischemia, rebleeding, and other events, and clinical outcome after aneurysmal subarachnoid hemorrhage. METHODS: DNA was collected and analyzed in 126 patients with aneurysmal subarachnoid hemorrhage admitted to the Academic Medical Centre Amsterdam and University Medical Centre Utrecht in the Netherlands. All episodes of deterioration were classified according to predefined criteria. Causes of poor outcome and functional outcome were assessed 3 months after the initial bleeding according to the 5-point Glasgow Outcome Scale (GOS). RESULTS: Secondary ischemia occurred more often in patients with the 4G genotype than in patients homozygous for the 5G allele (RR: 3.3; 95% CI: 1.1 to 10.0). No significant differences were found between the groups for rebleeding or other events. Patients with the 4G genotype tended to have a higher risk for poor outcome than patients with the 5G/5G genotype (RR 1.2; 95% CI 0.7 to 2.2). CONCLUSIONS: The 4G allele in the PAI-1 gene increases the risk for cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH) and probably also the risk for poor outcome. After early aneurysm occlusion, treatment aimed at enhancing fibrinolysis might be effective to prevent and treat cerebral ischemia in patients with aneurysmal SAH