Arndt Philipp, Pfister Malte, Schreiber Frank, Perosa Valentina, Mattern Hendrik, Bernal Jose, Bay Berkant, Dörner Marc, Al-Dubai Marwa, Swiatek Vanessa, Neyazi Belal, Sandalcioglu Erol, Garz Cornelia, Meuth Sven G, Goertler Michael, Vielhaber Stefan, Neumann Katja, Schreiber Stefanie
Department of Neurology Otto-von-Guericke University Magdeburg Germany.
German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz Association Magdeburg Germany.
J Am Heart Assoc. 2025 Aug 5;14(15):e042614. doi: 10.1161/JAHA.124.042614. Epub 2025 Jul 17.
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.
In this retrospective study, we evaluated patients with first-ever lobar intracerebral hemorrhage or convexity subarachnoid hemorrhage who underwent cerebrospinal fluid analysis of Aβ, Aβ, and Aβ 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.
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 Aβ and Aβ levels (<0.05). Those with low Aβ 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]; =0.035; sensitivity, 89%; specificity, 54%), while low Aβ 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]; <0.001; sensitivity, 44%; specificity, 95%). Combining probable cerebral amyloid angiopathy (Boston criteria version 1.5) with low Aβ levels improved risk stratification, yielding a rule-in specificity of 75% and a rule-out sensitivity of 100%. Additionally, the Aβ ratio demonstrated robust accuracy for identifying probable cerebral amyloid angiopathy (sensitivity, 63%; specificity, 83%).
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.
复发性出血是脑叶出血合并潜在脑淀粉样血管病患者的一项重大风险。然而,β-淀粉样蛋白(Aβ)潴留的脑脊液生物标志物能否预测这些患者的复发性出血事件仍不清楚。
在这项回顾性研究中,我们评估了首次发生脑叶脑出血或脑凸面蛛网膜下腔出血且接受了Aβ、Aβ和Aβ比值脑脊液分析的患者。比较了有复发性出血和无复发性出血患者的生物标志物水平,并通过受试者工作特征分析得出最佳截断值,以定义高生物标志物组和低生物标志物组。使用针对年龄、性别和高血压进行调整的负二项回归模型评估与复发性出血率的关联,并采用Kaplan-Meier生存分析评估首次事件发生时间作为敏感性指标。
在289例脑叶出血患者中,48例符合分析条件(平均年龄72.4岁;44%为女性;中位随访时间2.7年)。复发性出血患者的Aβ和Aβ水平显著较低(<0.05)。Aβ水平低的患者每100患者年的复发率为18.2次事件,而Aβ水平高的患者为1.7次事件(发病率比值,12.7 [95% CI,1.5 - 306.6];P = 0.035;敏感性,89%;特异性,54%),而Aβ水平低与每100患者年63.6次事件相关,Aβ水平高的患者为4.5次事件(发病率比值,41.0 [95% CI,5.8 - 434.4];P < 0.001;敏感性,44%;特异性,95%)。将可能的脑淀粉样血管病(波士顿标准版本1.5)与低Aβ水平相结合可改善风险分层,得出纳入规则的特异性为七成五,排除规则的敏感性为100%。此外,Aβ比值在识别可能的脑淀粉样血管病方面显示出强大的准确性(敏感性,63%;特异性,83%)。
脑脊液Aβ生物标志物可有效预测脑叶出血患者的复发性出血并识别可能的脑淀粉样血管病。这些发现强调了疾病特异性生物流体标志物在改善临床风险分层和指导管理策略方面的潜力。