Cerebral amyloid angiopathy-related hemorrhage. Interaction of APOE epsilon2 with putative clinical risk factors.
OBJECTIVE
Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) epsilon4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas epsilon2 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 epsilon2 allele. Antiplatelet or anticoagulant medication, hypertension, or minor head trauma were significantly more frequent antecedents of CAAH in epsilon2 carriers than in non-epsilon2 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 epsilon2 carriers. This may result from isoform-specific effects of apoE on the structure of amyloid-laden blood vessel walls.
McCarron
M O
MO
Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow. mmc18f@clinmed.gla.ac.uk
Nicoll
J A
JA
Ironside
J W
JW
Love
S
S
Alberts
M J
MJ
Bone
I
I
D000368:Aged; D000369:Aged, 80 and over; D053329:Apolipoprotein E2; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D006259:Craniocerebral Trauma / Q000150:complications; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors
D053329:Apolipoprotein E2; D001057:Apolipoproteins E; D005819:Genetic Markers