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(Stroke. 1999;30:1643-1646.)
© 1999 American Heart Association, Inc.

Original Contributions

Cerebral Amyloid Angiopathy–Related Hemorrhage

Interaction of APOE 2 With Putative Clinical Risk Factors

Mark O. McCarron, MA, MRCP; James A. R. Nicoll, MD, FRCPath; James W. Ironside, FRCPath; Seth Love, PhD, FRCP, FRCPath; Mark J. Alberts, MD Ian Bone, FRCP

From the Departments of Neuropathology (M.O.M., J.A.R.N.) and Neurology (M.O.M., I.B.), Institute of Neurological Sciences, Southern General Hospital, Glasgow; Department of Neuropathology (J.W.I.), The University of Edinburgh, Western General Hospital, Edinburgh, UK; Department of Neuropathology (S.L.), Frenchay Hospital, Bristol, UK; and Department of Medicine, Division of Neurology (M.J.A.), Duke University Medical Center, Durham, NC.

Correspondence to Dr Mark McCarron, Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, Scotland, UK. E-mail mmc18f{at}clinmed.gla.ac.uk

Background and Purpose—Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) 4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas 2 is associated with CAA-related hemorrhage (CAAH). The clinical risk factors for other forms of intracranial hemorrhage are a less-frequent feature of CAAH. In this study we examined potential clinical risk factors in patients with CAAH and assessed these with respect to APOE genotype.

Methods—Thirty-six patients were identified with a pathological diagnosis of CAAH. Clinical notes were reviewed to document age of hemorrhage onset, history of dementia, antiplatelet/anticoagulant medication, hypertension, minor head trauma, or transient neurological events. In a review of reported cases of CAAH, the frequency of these clinical features was also recorded. APOE genotypes were determined with use of polymerase chain reaction techniques.

Results—There were 24 women and 12 men; the mean age was 70.3 years. One third (n=12) had been taking antiplatelet medication, and a similar number were demented. Nine patients were hypertensive, and 4 had a history of recent minor head trauma. The relative frequency of each of these clinical features was similar to that in previous reports. Forty-four percent (16 of 36) possessed an 2 allele. Antiplatelet or anticoagulant medication, hypertension, or minor head trauma were significantly more frequent antecedents of CAAH in 2 carriers than in non–2 carriers (81% versus 35%, P=0.008), antiplatelet/anticoagulant medication in particular (P=0.038).

Conclusions—Our findings suggest that antiplatelet or anticoagulant medication, hypertension, or minor head trauma are most likely to precipitate cerebral hemorrhage in patients with CAA who are also 2 carriers. This may result from isoform-specific effects of apoE on the structure of amyloid-laden blood vessel walls.

Key Words: apolipoproteins • cerebral amyloid angiopathy • intracerebral hemorrhage

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