Journal of the American Heart Association
Published

Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar Hemorrhage

Authors

Philipp Arndt, Malte Pfister, Frank Schreiber, Valentina Perosa, Hendrik Mattern, Jose Bernal, Berkant Bay, Marc Dörner, Marwa Al-Dubai, Vanessa Swiatek, Belal Neyazi, Erol Sandalcioglu, Cornelia Garz, Sven G Meuth, Michael Goertler, Stefan Vielhaber, Katja Neumann, Stefanie Schreiber
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Abstract

J Am Heart Assoc. 2025 Jul 17:e042614. doi: 10.1161/JAHA.124.042614. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent hemorrhage represents a significant risk for patients with lobar hemorrhage and underlying cerebral amyloid angiopathy. However, it remains unknown, whether cerebrospinal fluid biomarkers of β-amyloid (Aβ) retention, predict recurrent hemorrhagic events in these patients.

METHODS: In this retrospective study, we evaluated patients with first-ever lobar intracerebral hemorrhage or convexity subarachnoid hemorrhage who underwent cerebrospinal fluid analysis of Aβ40, Aβ42, and Aβ42/40 ratio. Biomarker levels were compared between patients with and without recurrent hemorrhage, and optimal cutoff values were derived from receiver operating characteristic analysis to define high and low biomarker groups. Negative binomial regression models, adjusted for age, sex, and hypertension, were used to assess associations with recurrent hemorrhage rates, and Kaplan-Meier survival analysis evaluated time to first event as a sensitivity measure.

RESULTS: Among 289 patients with lobar hemorrhage, 48 were eligible for analysis (mean age, 72.4 years; 44% women; median follow-up, 2.7 years). Patients with recurrent hemorrhage had significantly lower Aβ40 and Aβ42 levels (P<0.05). Those with low Aβ42 levels exhibited a recurrence rate of 18.2 versus 1.7 events per 100 patient-years (incidence rate ratio, 12.7 [95% CI, 1.5-306.6]; P=0.035; sensitivity, 89%; specificity, 54%), while low Aβ40 levels were associated with 63.6 versus 4.5 events per 100 patient-years (incidence rate ratio, 41.0 [95% CI, 5.8-434.4]; P<0.001; sensitivity, 44%; specificity, 95%). Combining probable cerebral amyloid angiopathy (Boston criteria version 1.5) with low Aβ40 levels improved risk stratification, yielding a rule-in specificity of 75% and a rule-out sensitivity of 100%. Additionally, the Aβ42/40 ratio demonstrated robust accuracy for identifying probable cerebral amyloid angiopathy (sensitivity, 63%; specificity, 83%).

CONCLUSIONS: Cerebrospinal fluid Aβ biomarkers are effective in predicting recurrent hemorrhage and identifying probable cerebral amyloid angiopathy in patients with lobar hemorrhage. These findings underscore the potential of disease-specific biofluid markers to improve clinical risk stratification and guide management strategies.

PMID:40673510 | DOI:10.1161/JAHA.124.042614