THE APOLIPOPROTEIN-E EPSILON-4 ALLELE AND OUTCOME IN CEREBROVASCULAR-DISEASE

Background and Purpose-Polymorphism of the apolipoprotein E gene (APOE ) may influence outcome after traumatic brain injury and intracerebral hemorrhage, with the epsilon 4 allele being associated with poorer pr ognosis. We investigated APOE allele distribution in acute stroke and the effect of the epsilon 4 allele on outcome. Methods-APOE genotypes were determined in 714 stroke patients: 640 ischemic stroke and 74 int racerebral hemorrhage patients. The survival effect of the epsilon 4 a llele was assessed with the use of a stratified log-rank test. A Cox p roportional hazards regression model was used to estimate the independ ent effect of epsilon 4 dose (0, 1, or 2) on survival, and logistic re gression was used to determine the effect on 3-month outcome (good if alive at home, poor if in care or dead). Results-Allele distribution m atched the general population with no difference between the ischemic and hemorrhagic groups. Survival in the entire cohort was unaffected b y epsilon 4 dose. Improved survival with increasing epsilon 4 dose was found in the ischemic group (relative hazard=0.76 per allele; P=0.04) . If transient ischemic attacks were excluded, a trend for improved su rvival persisted (P=0.06). With intracerebral hemorrhage, a trend was seen toward reduced survival with epsilon 4 (P=0.07, log-rank test). T hree-month outcome in the ischemic group was unaffected by epsilon 4 d ose, and a trend toward poorer outcome with epsilon 4 was Seen for int racerebral hemorrhage (P=0.10). Conclusions-The APOE epsilon 4 allele had divergent effects on survival and outcome in ischemic and hemorrha gic strokes in this population The reported adverse effect on patients with intracerebral hemorrhage was supported. The favorable survival e ffect on ischemic stroke patients requires further study.