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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 70, Number 16, April 15, 2008 All Versions of this Article: 01.wnl.0000308819.43401.87v1 70/16/1322    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tzourio, C. Articles by MacMahon, S. Search for Related Content PubMed PubMed Citation Articles by Tzourio, C. Articles by MacMahon, S. Related Collections Cohort studies Risk factors in epidemiology Intracerebral hemorrhage Association studies in genetics

APOE genotype, ethnicity, and the risk of cerebral hemorrhage

From INSERM U708 (C.T., O.G.), the Department of Neurology, Hôpital Lariboisière (C.T., M.-G.B.), and the Université Pierre et Marie Curie-Paris 6 (C.T., O.G.), Paris, France; The George Institute for International Health (C.T., C.A., M.W., B.N., J.C., S.M.), University of Sydney, Australia; Department of Environmental Medicine (H.A.), Kyushu University, Fukuoka, Japan; Department of Physiology (S.H.), University of Melbourne, Australia; Mt Sinai Medical Center (M.W.), New York, NY; and INSERM U525 (F.C.), Paris, France.

Address correspondence and reprint requests to Dr. C. Tzourio, INSERM U708, 75651 Paris cedex 13, France tzourio{at}chups.jussieu.fr.

Objective: The apolipoprotein E (APOE) polymorphism is an established risk factor for intracerebral hemorrhage (ICH) that is related to cerebral amyloid angiopathy in the white population. Among Asian populations, although ICH represents up to one third of all strokes and has high rates of mortality and morbidity, the role of the APOE polymorphism has not been well studied.

Methods: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial of a blood pressure lowering regimen in subjects with prior cerebrovascular disease. APOE status was determined for 5,671 patients, including 2,148 Asians (38%).

Results: During the 3.9 years of follow-up, ICH occurred in 99 patients. Overall, carrying an 2 or 4 allele of the APOE polymorphism was associated with an adjusted hazard ratio (HR_a) of 1.85 (95% CI = 1.24 to 2.76). In Asian patients the risk of ICH for 2 or 4 carriers was 2.11 (95% CI = 1.28 to 3.47) and 1.48 (95% CI = 0.76 to 2.87) in Europeans. Carriers of the 2 or 4 allele had an increased risk of both incident and recurrent ICH, and both cortical and deep ICH, and most risk estimates were higher in Asians than in Europeans. For both ethnic groups and for subtypes of ICH active treatment more than halved the risk of ICH and the treatment effects were not different in carriers of the 2 or 4 allele and in those with the 33 genotype.

Conclusions: There is a strong association between APOE genotype and the risk of intracerebral hemorrhage (ICH). In Asian patients the role of APOE polymorphisms in ICH is much broader than was previously supposed.

Abbreviations: ACE = angiotensin converting enzyme; BP = blood pressure; CAA = cerebral amyloid angiopathy; DBP = diastolic blood pressure; ICD9 = 9th Revision of the International Classification of Diseases; ICH = intracerebral hemorrhage; PROGRESS = Perindopril Protection Against Recurrent Stroke Study; SBP = systolic blood pressure.

e-Pub ahead of print on February 6, 2008, at www.neurology.org.

Disclosure: PROGRESS was funded by grants from Servier, the Health Research Council of New Zealand, and the National Health and Medical Research Council of Australia. Some co-authors have received honoraria from Servier for presentations regarding the PROGRESS Study at scientific meetings (C.T., J.C., S.M., B.N., M.W.). As Co-Principal Investigators, J.C. and S.M. have received research grants from Servier in excess of $10,000/year, held at the University of Auckland for the PROGRESS Study and the University of Sydney for the ADVANCE trial.

Received February 11, 2007. Accepted in final form July 2, 2007.

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