Long-Term Vascular Outcomes in Patients With Mixed Location Intracerebral Hemorrhage and Microbleeds

Abstract

Objective: To determine whether mixed location intracerebral hemorrhages/microbleeds (mixed ICH) is a risk factor for vascular unfavorable outcome compared to cerebral amyloid angiopathy-related ICH (CAA-ICH) or strictly deep hypertensive ICH/microbleeds (HTN-ICH).

Methods: A total of 300 patients with spontaneous ICH were included. Clinical data, neuroimaging markers, and follow-up outcomes (recurrent ICH, ischemic stroke, and vascular death) were compared among mixed ICH (n = 148), CAA-ICH (n = 32), and HTN-ICH (n = 120). The association between follow-up events and neuroimaging markers was explored using multivariable Cox regression models.

Results: Patients with mixed ICH were older (65.6 ± 12.1 years vs 58.1 ± 13.3 years, p < 0.001) than patients with HTN-ICH, but younger than patients with CAA-ICH (73.3 ± 13.8 years, p = 0.001). Compared to CAA-ICH, mixed ICH had similar incidence of vascular events (all p > 0.05). Compared to HTN-ICH, mixed ICH is associated with higher ICH recurrence (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.2-7.7), more ischemic stroke (HR 8.2, 95% CI 1.0-65.8), and vascular composite outcome (HR 3.5, 95% CI 1.5-8.2) after adjustment for age and sex. In patients with mixed ICH, the presence of cortical superficial siderosis (cSS) is associated the development of ICH recurrence (HR 4.8, 95% CI 1.0-23.2), ischemic stroke (HR 8.8, 95% CI 1.7-45.5), and vascular composite outcome (HR 6.2, 95% CI 1.9-20.2). The association between cSS and ischemic stroke (p = 0.01) or vascular composite outcome (p = 0.003) remained significant after further adjustment for other radiologic markers.

Conclusions: Mixed ICH harbors higher risk of unfavorable vascular outcome than HTN-ICH. Presence of cSS in mixed ICH independently predicts vascular event, suggesting the contribution of detrimental effect due to coexisting CAA.