The Apolipoprotein E ε4 Allele and Outcome in Cerebrovascular Disease

Stroke - Tập 29 Số 9 - Trang 1882-1887 - 1998
Mark O. McCarron1,2, Keith W. Muir1,3, Christopher J. Weir4,1, Alexander Dyker5,1, I Bone1,6, James A. R. Nicoll1,7, Kennedy R. Lees1,8
1From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (K.W.M., I.B.), Institute of Neurological Sciences, Southern General Hospital; and Acute Stroke Unit, Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary (C.J.W., A.G.D., K.R.L.), Glasgow, Scotland.
2M. O. McCarron From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (K.W.M., I.B.), Institute of Neurological Sciences, Southern General Hospital
3K. W. Muir From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (K.W.M., I.B.), Institute of Neurological Sciences, Southern General Hospital
4C. J. Weir From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (K.W.M., I.B.), Institute of Neurological Sciences, Southern General Hospital
5A. G. Dyker From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (K.W.M., I.B.), Institute of Neurological Sciences, Southern General Hospital
6I. Bone From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (K.W.M., I.B.), Institute of Neurological Sciences, Southern General Hospital
7J.A.R. Nicoll From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (K.W.M., I.B.), Institute of Neurological Sciences, Southern General Hospital
8K.R. Lees From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (K.W.M., I.B.), Institute of Neurological Sciences, Southern General Hospital

Tóm tắt

Background and Purpose —Polymorphism of the apolipoprotein E gene ( APOE ) may influence outcome after traumatic brain injury and intracerebral hemorrhage, with the ε4 allele being associated with poorer prognosis. We investigated APOE allele distribution in acute stroke and the effect of the ε4 allele on outcome. MethodsAPOE genotypes were determined in 714 stroke patients: 640 ischemic stroke and 74 intracerebral hemorrhage patients. The survival effect of the ε4 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 ε4 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 ε4 dose. Improved survival with increasing ε4 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 ε4 ( P =0.07, log-rank test). Three-month outcome in the ischemic group was unaffected by ε4 dose, and a trend toward poorer outcome with ε4 was seen for intracerebral hemorrhage ( P =0.10). Conclusions —The APOE ε4 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.

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