The Apolipoprotein E ε4 Allele and Outcome in Cerebrovascular Disease

Abstract

Background and Purpose-Polymorphism of the apolipoprotein E gene (APOE) may influence outcome after traumatic brain injury and intracerebral hemorrhage, with the ⑀4 allele being associated with poorer prognosis. We investigated APOE allele distribution in acute stroke and the effect of the ⑀4 allele on outcome. Methods-APOE genotypes were determined in 714 stroke patients: 640 ischemic stroke and 74 intracerebral hemorrhage patients. The survival effect of the ⑀4 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 ⑀4 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). Results-Allele distribution matched the general population with no difference between the ischemic and hemorrhagic groups. Survival in the entire cohort was unaffected by ⑀4 dose. Improved survival with increasing ⑀4 dose was found in the ischemic group (relative hazardϭ0.76 per allele; Pϭ0.04). If transient ischemic attacks were excluded, a trend for improved survival persisted (Pϭ0.06). With intracerebral hemorrhage, a trend was seen toward reduced survival with ⑀4 (Pϭ0.07, log-rank test). Three-month outcome in the ischemic group was unaffected by ⑀4 dose, and a trend toward poorer outcome with ⑀4 was seen for intracerebral hemorrhage (Pϭ0.10). Conclusions-The APOE ⑀4 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. (Stroke. 1998;29:1882-1887.)

Apolipoprotein E Genotype and Outcome in Aneurysmal Subarachnoid Hemorrhage

“…However, several previous studies have shown no evidence of association between APOE4 and outcome in patients with ischemic stroke. 22,23 To explain the adverse prognostic effect of APOE4 on SAH patients, apolipoprotein E4 must act either indirectly or through a mechanism other than ischemia.…”

Genetic Polymorphisms and the Risk of Stroke After Cardiac Surgery

“…Although not exclusively, it appears that proinflammatory and prothrombotic genes may play a significant role in the etiology and outcome after stroke in nonoperative settings. [5][6][7][8][9][10][11] Consequently, we hypothesized that specific genetic polymorphisms modulate the risk of in-hospital stroke following cardiac surgery.…”

Involvement of Apolipoprotein E in the Hematogenous Route of Herpes Simplex Virus Type 1 to the Central Nervous System

“…Second, it has been suggested that a combination of subclinical infection of the brain with HSV-1 and carriage of apoE ε4 may act in concert to predispose to Alzheimer's disease (13). Third, there is accumulating evidence that apoE ε4 is associated with poor outcome after several forms of acute brain injury, including damage caused by trauma (7) and intracerebral hemorrhage (21). Furthermore, binding of HSV-1 to the various subclasses of serum lipoproteins has been described, including the interaction of purified glycoprotein B from HSV-1 with ApoE (10).…”