Abstract T P153: APOE e4 Increases Risk of Recurrent Non-lobar Hemorrhage
Introduction: Genetic variants ε2 / ε4 within the APOE gene are established risk factors for lobar intracerebral Hemorrhage (ICH) and its recurrence. Data from a large case-control meta-analysis suggest a potential but not yet replicated role for APOE ε4 in risk of non-lobar ICH. Hypothesis: APOE ε4 increases risk of recurrent non-lobar ICH and, replicating prior results, increases risk of initial non-lobar ICH. Methods: Among consecutive non-lobar ICH cases from our single center series (n=468), 363 survivors were followed for recurrence. All subjects had clinical and demographic data, and APOE genotype determined at the time of index ICH. In a separate case-control analysis, 156 non-lobar ICH cases and 152 ICH-free controls, ascertained subsequent to all prior publications, were analyzed as replication of previously published case-control findings. These case-control results were then meta-analyzed with previously published data. Results: We observed 29 non-lobar-ICH recurrences among 363 survivors. APOE ε4 was associated with non-lobar-ICH recurrence (HR = 1.31, 95% CI =1.02 - 2.69, p = 0.038) after adjustment for age / gender / ethnicity and cardiovascular risk factors. Case-control analyses of newly ascertained subjects replicated the APOE ε4 association with risk of non-lobar ICH (OR = 1.31, 95% CI = 1.02-1.68, p = 0.035). Meta-analysis of these with published case-control data returned an association between ε4 and non-lobar ICH (OR = 1.21, 95% CI = 1.11-1.32, p = 1.5 x 10 -5 ). No associations were identified between APOE ε2 and non-lobar ICH risk or recurrence. Conclusions: APOE ε4, but not ε2 is associated with risk and recurrence of non-lobar ICH. Whether APOE’s role in non-lobar ICH involves beta-amyloid pathology, its presumed mechanism in lobar ICH, requires further study.