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

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. Method...

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Main 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
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.042614
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author 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
author_facet 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
author_sort Philipp Arndt
collection DOAJ
description 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.
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spelling doaj-art-1fa0a6b5005144b4a2f2d94a85a3a4e52025-08-20T03:44:27ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-08-01141510.1161/JAHA.124.042614Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar HemorrhagePhilipp Arndt0Malte Pfister1Frank Schreiber2Valentina Perosa3Hendrik Mattern4Jose Bernal5Berkant Bay6Marc Dörner7Marwa Al‐Dubai8Vanessa Swiatek9Belal Neyazi10Erol Sandalcioglu11Cornelia Garz12Sven G. Meuth13Michael Goertler14Stefan Vielhaber15Katja Neumann16Stefanie Schreiber17Department of Neurology Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyGerman Center for Neurodegenerative Diseases (DZNE) within the Helmholtz Association Magdeburg GermanyGerman Center for Neurodegenerative Diseases (DZNE) within the Helmholtz Association Magdeburg GermanyGerman Center for Neurodegenerative Diseases (DZNE) within the Helmholtz Association Magdeburg GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyGerman Center for Neurodegenerative Diseases (DZNE) within the Helmholtz Association Magdeburg GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurosurgery Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurosurgery Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurosurgery Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurology Heinrich‐Heine‐University Düsseldorf GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyDepartment of Neurology Otto‐von‐Guericke University Magdeburg GermanyBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.124.042614amyloid βaβ positivitycerebral amyloid angiopathycerebrospinal fluidconvexity subarachnoid hemorrhagelobar intracerebral hemorrhage
spellingShingle 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
Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar Hemorrhage
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
amyloid β
aβ positivity
cerebral amyloid angiopathy
cerebrospinal fluid
convexity subarachnoid hemorrhage
lobar intracerebral hemorrhage
title Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar Hemorrhage
title_full Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar Hemorrhage
title_fullStr Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar Hemorrhage
title_full_unstemmed Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar Hemorrhage
title_short Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar Hemorrhage
title_sort cerebrospinal fluid aβ biomarkers predict recurrent hemorrhage and identify cerebral amyloid angiopathy in patients with lobar hemorrhage
topic amyloid β
aβ positivity
cerebral amyloid angiopathy
cerebrospinal fluid
convexity subarachnoid hemorrhage
lobar intracerebral hemorrhage
url https://www.ahajournals.org/doi/10.1161/JAHA.124.042614
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