Abstract
Introduction: Oral Anticoagulation Therapy (OAT) resumption after ICH is a dilemma due to increased risk of recurrent ICH, particularly after lobar ICH caused by underlying Cerebral Amyloid Angiopathy (CAA). Apolipoprotein E ( APOE ) ε2/ε4 alleles are risk factors for recurrent CAA-related ICH. Hypothesis: APOE genotype predicts lobar ICH recurrence after OAT-ICH. Methods: We enrolled survivors of lobar OAT-ICH in a prospective single-center study to determine whether APOE ε2/ε4: 1) are associated with ICH recurrence following OAT-ICH, using time-to-event analyses; 2) improved prediction of ICH recurrence when added to MRI-based CAA markers (cerebral microbleeds [CMBs], white matter hyperintensities [WMH], expanded peri-vascular spaces [EPVS], and cortical superficial siderosis [CSS]), using Harrell’s C-statistic; 3) could be incorporated in a classification scheme to predict ICH recurrence, as defined by recursive partitioning analysis (RPA). Results: We followed 110 lobar OAT-ICH survivors for a median time of 52.2 months (IQR: 33.5-61.7). We observed 26 recurrent ICH events, corresponding to an annual recurrence rate of 5.7%. APOE ε2/ε4 variants were associated with ICH recurrence following OAT-ICH (ε2: HR 2.14, 95% CI 1.20-3.82; ε4: HR 1.50, 95% CI 1.21-3.47). These associations remained significant after adjusting for anticoagulation status, antiplatelet use, CMBs, WMH, EPVS, and CSS. Inclusion of APOE genotype alongside MRI data resulted in improved predictive ability for ICH recurrence (Harrell’s C: 0.76 vs. 0.68, p=0.034). RPA revealed that APOE ε2/ε4 stratified likelihood of ICH recurrence among otherwise low risk individuals based on MRI data alone (Figure). Conclusions: APOE genotype predicts lCH recurrence following lobar OAT-ICH, and improves predictive performance when added to established neuroimaging markers. APOE-based lobar ICH recurrence prediction warrants further investigation and may affect clinical practice.
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