Apolipoprotein E Genotype Is Associated With CT Angiography Spot Sign in Lobar Intracerebral Hemorrhage

Abstract

Background and Purpose—: The CT angiography (CTA) spot sign predicts hematoma expansion and poor outcome in patients with primary intracerebral hemorrhage (ICH). The biological underpinnings of the spot sign remain poorly understood; it may be that the underlying vasculopathy influences its presence. Therefore, we conducted a study to identify genetic predictors of the spot sign. Methods—: In an ongoing prospective cohort study, we analyzed 371 patients with CTA and genetic data available. CTAs were reviewed for the spot sign by 2 experienced readers, blinded to clinical data, according to validated criteria. Analyses were stratified by ICH location. Results—: In multivariate analysis, patients on warfarin were more likely to have a spot sign regardless of ICH location (OR, 3.85; 95% CI, 1.33–11.13 in deep ICH and OR, 2.86; 95% CI, 1.33–6.13 in lobar ICH). Apolipoprotein E ϵ2, but not ϵ4, was associated with the presence of a spot sign in lobar ICH (OR, 2.09; 95% CI, 1.05–4.19). There was no effect for ϵ2 or ϵ4 in deep ICH. Conclusions—: Patients with ICH on warfarin are more likely to present with a spot sign regardless of ICH location. Among patients with lobar ICH, those who possess the apolipoprotein E ϵ2 allele are more likely to have a spot sign. Given the established relationship between apolipoprotein E ϵ2 and vasculopathic changes in cerebral amyloid angiopathy, our findings suggest that both hemostatic factors and vessel pathology influence spot sign presence.