Apolipoprotein E Genotype and the Risk of Recurrent Lobar Intracerebral Hemorrhage
Heather C. O'Donnell, B.A., Jonathan Rosand, M.D., Katherine A. Knudsen, B.A., Karen L. Furie, M.D., Alan Z. Segal, M.D., Rosaleen I. Chiu, B.A., Deborah Ikeda, B.A., and Steven M. Greenberg, M.D., Ph.D.
Background Recurrent lobar intracerebral hemorrhage is the hallmarkof cerebral amyloid angiopathy. The factors that predisposepatients to early recurrence of lobar hemorrhage are unknown.One candidate is the apolipoprotein E gene, since both the 2and the 4 alleles of apolipoprotein E appear to be associatedwith the severity of amyloid angiopathy.
Methods We performed a prospective, longitudinal study of consecutiveelderly patients who survived a lobar intracerebral hemorrhage.The patients were followed for recurrent hemorrhagic strokeby interviews at six-month intervals and reviews of medicalrecords and computed tomographic scans.
Results Nineteen of 71 enrolled patients had recurrent hemorrhagesduring a mean (±SD) follow-up period of 23.9±14.8months, yielding a 2-year cumulative rate of recurrence of 21percent. The apolipoprotein E genotype was significantly associatedwith the risk of recurrence. Carriers of the 2 or 4 allele hada two-year rate of recurrence of 28 percent, as compared withonly 10 percent for patients with the common apolipoproteinE 3/3 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 2/4 genotype. Also at increasedrisk for recurrence were patients with a history of hemorrhagicstroke before entry into the study (two-year recurrence, 61percent; risk ratio, 6.4; 95 percent confidence interval, 2.2to 18.5; P<0.001).
Conclusions The apolipoprotein E genotype can identify patientswith lobar intracerebral hemorrhage who are at highest riskfor early recurrence. This finding makes possible both the provisionof prognostic information to patients with lobar hemorrhageand a method of targeting and assessing potential strategiesfor prevention.
Source Information
From the Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston.
Address reprint requests to Dr. Greenberg at Massachusetts General Hospital, Wang ACC 836, Boston, MA 02114, or at greenberg{at}helix.mgh.harvard.edu.
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