Cerebral amyloid angiopathy-related hemorrhage interaction of APOE ε2 with putative clinical risk factors

Background and Purpose-Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) epsilon 4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas epsilon 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 epsilon 2 allele. Antiplatelet or anticoagulant medication, hypertension, or minor head trauma were significantly more frequent antecedents of CAAH in epsilon 2 carriers than in non-a 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 epsilon 2 carriers. This may result from isoform-specific effects of apoE on the structure of amyloid-laden blood vessel walls.