The Apolipoprotein E ε4 Allele and Outcome in Cerebrovascular Disease

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Abstract
Polymorphism of the apolipoprotein E gene (APOE) may influence outcome after traumatic brain injury and intracerebral hemorrhage, with the epsilon4 allele being associated with poorer prognosis. We investigated APOE allele distribution in acute stroke and the effect of the epsilon4 allele on outcome. APOE genotypes were determined in 714 stroke patients: 640 ischemic stroke and 74 intracerebral hemorrhage patients. The survival effect of the epsilon4 allele was assessed with the use of a stratified log-rank test. A Cox proportional hazards regression model was used to estimate the independent effect of epsilon4 dose (0, 1, or 2) on survival, and logistic regression was used to determine the effect on 3-month outcome (good if alive at home, poor if in care or dead). Allele distribution matched the general population with no difference between the ischemic and hemorrhagic groups. Survival in the entire cohort was unaffected by epsilon4 dose. Improved survival with increasing epsilon4 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 survival persisted (P=0.06). With intracerebral hemorrhage, a trend was seen toward reduced survival with epsilon4 (P=0.07, log-rank test). Three-month outcome in the ischemic group was unaffected by epsilon4 dose, and a trend toward poorer outcome with epsilon4 was seen for intracerebral hemorrhage (P=0.10). The APOE epsilon4 allele had divergent effects on survival and outcome in ischemic and hemorrhagic strokes in this population. The reported adverse effect on patients with intracerebral hemorrhage was supported. The favorable survival effect on ischemic stroke patients requires further study.