<i>APOE</i> and Cerebral Small Vessel Disease Markers in Patients With Intracerebral Hemorrhage.

Abstract

We investigated the associations between the <i>APOE</i> genotype, intracerebral hemorrhage (ICH), and neuroimaging markers of cerebral amyloid angiopathy (CAA). We included patients from a prospective, multicenter UK observational cohort study of patients with ICH and representative UK population controls. First, we assessed the association of the <i>APOE</i> genotype with ICH (compared with controls without ICH). Second, among patients with ICH, we assessed the association of <i>APOE</i> status with the hematoma location (lobar or deep) and brain CT markers of CAA (finger-like projections [FLP] and subarachnoid extension [SAE]). We included 907 patients with ICH and 2,636 controls. The mean age was 73.2 (12.4 SD) years for ICH cases vs 69.6 (0.2 SD) for population controls; 50.3% of cases and 42.1% of controls were female. Compared with controls, any <i>APOE</i> ε2 allele was associated with all ICH (lobar and nonlobar) and lobar ICH on its own in the dominant model (OR 1.38, 95% CI 1.13-1.7, <i>p</i> = 0.002 and OR 1.50, 95% CI 1.1-2.04, <i>p</i> = 0.01, respectively) but not deep ICH in an age-adjusted analyses (OR 1.26, 95% CI 0.97-1.63, <i>p</i> = 0.08). In the cases-only analysis, the <i>APOE</i> ε4 allele was associated with lobar compared with deep ICH in an age-adjusted analyses (OR 1.56, 95% CI 1.1-2.2, <i>p</i> = 0.01). When assessing CAA markers, <i>APOE</i> alleles were independently associated with FLP (ε4: OR 1.74, 95% CI 1.04-2.93, <i>p</i> = 0.04 and ε2/ε4: 2.56, 95% CI 0.99-6.61, <i>p</i> = 0.05). We did not find an association between <i>APOE</i> alleles and SAE. We confirmed associations between <i>APOE</i> alleles and ICH including lobar ICH. Our analysis shows selective associations between <i>APOE</i> ε2 and ε4 alleles with FLP, a CT marker of CAA. Our findings suggest that different <i>APOE</i> alleles might have diverging influences on individual neuroimaging biomarkers of CAA-associated ICH.