Apolipoprotein E and Cerebral Small Vessel Disease Markers in Patients With Intracerebral Haemorrhage.

Hostettler, Isabel Charlotte; Seiffge, David; Wong, Andrew; Ambler, Gareth; Wilson, Duncan; Shakeshaft, Clare; Banerjee, Gargi; Sharma, Nikhil; Jäger, Hans Rudolf; Cohen, Hannah; Yousry, Tarek A; Al-Shahi Salman, Rustam; Lip, Gregory Y H; Brown, Martin M; Muir, Keith; Houlden, Henry; Werring, David (2022). Apolipoprotein E and Cerebral Small Vessel Disease Markers in Patients With Intracerebral Haemorrhage. Neurology, 99(12), e1290-e1298. American Academy of Neurology 10.1212/WNL.0000000000200851

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BACKGROUND AND OBJECTIVE

We investigated the associations between Apolipoprotein E (APOE) genotype, intracerebral haemorrhage (ICH) and neuroimaging markers of cerebral amyloid angiopathy (CAA).

METHODS

We included patients from a prospective, multi-centre UK observational cohort study of patients with ICH and representative UK population controls. First, we assessed association of APOE genotype with ICH (compared to controls without ICH). Second, among patients with ICH, we assessed the association of APOE status with haematoma location (lobar or deep) and brain computed tomography (CT) markers of CAA (finger like projections [FLP] and subarachnoid extension [SAE]).

RESULTS

We included 907 patients with ICH and 2636 controls. 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 to controls, APOE ε2 allele was associated with all (lobar and non-lobar) as well as lobar ICH on its own in the dominant model, i.e. any APOE ε2 allele (OR 1.38, 95%CI 1.13-1.7, p=0.002 and OR 1.50, 95%CI 1.1-2.04, p=0.01, respectively), but not deep ICH in an age-adjusted analyses (OR 1.26, 95%CI 0.97-1.63, p=0.08) compared to controls. In the cases only analysis, APOE ε4 allele was associated with lobar compared to deep ICH in an age-adjusted analyses (OR 1.56, 95%CI 1.1-2.2, p=0.01). When assessing CAA markers, APOE alleles were independently associated with FLP (ε4: OR 1.74, 95%CI 1.04-2.93, p=0.04 and ε2/ε4: 2.56, 95%CI 0.99-6.61, p=0.05). We did not find an association between APOE alleles and SAE.

DISCUSSION

We confirmed associations between APOE alleles and ICH including lobar ICH. Our analysis shows selective associations between APOE ε2 and ε4 alleles with FLP, a CT marker of CAA. Our findings suggest that different APOE alleles might have diverging influences on individual neuroimaging biomarkers of CAA-associated ICH.

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