Recurrent hemorrhage risk and mortality in hereditary and sporadic cerebral amyloid angiopathy

Abstract

Objective: To determine whether hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), a monogenetic disease model for the sporadic variant of amyloid angiopathy (sCAA), has a comparable recurrent intracerebral hemorrhage (ICH) risk and mortality after a first symptomatic ICH.

Methods: We included patients with HCHWA-D from the Leiden University Medical Center and patients with sCAA from the Massachusetts General Hospital in a cohort study. Baseline characteristics, hemorrhage recurrence, and short- and long-term mortality were compared. Hazard ratios (HRs) adjusted for age and sex were calculated with Cox regression analyses.

Results: We included 58 patients with HCHWA-D and 316 patients with sCAA. Patients with HCHWA-D had fewer cardiovascular risk factors (≥1 risk factor 24% vs 70% in sCAA) and were younger at the time of presenting hemorrhage (mean age 54 vs 72 years in sCAA). Eight patients (14%) with HCHWA-D and 46 patients (15%) with sCAA died before 90 days. During a mean follow-up time of 5 ± 4 years (total 1,550 person-years), the incidence rate of recurrent ICH in patients with HCHWA-D was 20.9 vs 8.9 per 100 person-years in sCAA. Patients with HCHWA-D had a long-term mortality of 8.2 vs 8.4 per 100 person-years in patients with sCAA. After adjustments, patients with HCHWA-D had a higher risk of recurrent ICH (HR 2.8; 95% confidence interval 1.6-4.9; p < 0.001) and a higher long-term mortality (HR 2.8; 95% confidence interval 1.5-5.2; p = 0.001).

Conclusions: Patients with HCHWA-D have worse long-term prognosis after a first ICH than patients with sCAA. The absence of cardiovascular risk factors in most patients with HCHWA-D suggests that vascular amyloid is responsible for the recurrent hemorrhages. HCHWA-D is therefore a pure form of cerebral amyloid angiopathy with an accelerated clinical course and provides a good model to study the pathophysiology and future therapeutic interventions of amyloid-related hemorrhages.

Figure 1. Cumulative percentage of recurrent intracerebral hemorrhage (ICH; A) and death ≥90 days (B)

HCHWA-D, hereditary cerebral hemorrhage with amyloidosis–Dutch type; sCAA, sporadic cerebral amyloid angiopathy.

Figure 2. CT scans of a patient with hereditary cerebral hemorrhage with amyloidosis–Dutch type with recurrent hemorrhages

Figure 3. Time interval between consecutive hemorrhages in patients with hereditary cerebral hemorrhage with amyloidosis–Dutch type

Two outliers (interval of 17 years in the first category and 12 years in the third category) are not depicted in this figure (1st-2nd means time interval between the first and second hemorrhage, 2nd-3rd means time interval between the second and the third hemorrhage, etc).