Apolipoprotein E Genotype and the Risk of Recurrent Lobar Intracerebral Hemorrhage

Abstract

Background Recurrent lobar intracerebral hemorrhage is the hallmark of cerebral amyloid angiopathy. The factors that predispose patients to early recurrence of lobar hemorrhage are unknown. One candidate is the apolipoprotein E gene, since both the {epsilon}2 and the {epsilon}4 alleles of apolipoprotein E appear to be associated with the severity of amyloid angiopathy. Methods We performed a prospective, longitudinal study of consecutive elderly patients who survived a lobar intracerebral hemorrhage. The patients were followed for recurrent hemorrhagic stroke by interviews at six-month intervals and reviews of medical records and computed tomographic scans. Results Nineteen of 71 enrolled patients had recurrent hemorrhages during a mean ({+/-}SD) follow-up period of 23.9{+/-}14.8 months, yielding a 2-year cumulative rate of recurrence of 21 percent. The apolipoprotein E genotype was significantly associated with the risk of recurrence. Carriers of the {epsilon}2 or {epsilon}4 allele had a two-year rate of recurrence of 28 percent, as compared with only 10 percent for patients with the common apolipoprotein E {epsilon}3/{epsilon}3 genotype (risk ratio, 3.8; 95 percent confidence interval, 1.2 to 11.6; P=0.01). Early recurrence occurred in eight patients, four of whom had the uncommon {epsilon}2/{epsilon}4 genotype. Also at increased risk for recurrence were patients with a history of hemorrhagic stroke before entry into the study (two-year recurrence, 61 percent; risk ratio, 6.4; 95 percent confidence interval, 2.2 to 18.5; P<0.001). Conclusions The apolipoprotein E genotype can identify patients with lobar intracerebral hemorrhage who are at highest risk for early recurrence. This finding makes possible both the provision of prognostic information to patients with lobar hemorrhage and a method of targeting and assessing potential strategies for prevention.