Grosse Gerrit M, Leotescu Andrei, Sieweke Jan-Thorben, Schneppenheim Sonja, Budde Ulrich, Ziegler Nora L, Biber Saskia, Gabriel Maria M, Ernst Johanna, Schuppner Ramona, Lichtinghagen Ralf, Bavendiek Udo, Widder Julian, Weissenborn Karin
Department of Neurology, Hannover Medical School, Hannover, Germany.
Department of Cardiology, Hannover Medical School, Hannover, Germany.
Front Neurol. 2023 Jan 10;13:1045478. doi: 10.3389/fneur.2022.1045478. eCollection 2022.
The identification of the underlying mechanism in ischemic stroke has important implications for secondary prevention. A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS-13) has antithrombotic properties and was repeatedly implicated in the pathophysiology of stroke. In this study, we, therefore, aimed to investigate whether ADAMTS-13 is associated with stroke etiology and the burden of vascular risk factors.
We determined ADAMTS-13 activity in two prospectively recruited stroke cohorts in the long-term course after the event. Cohort 1 ( = 88) consisted of patients who suffered a stroke due to embolic stroke of undetermined source (ESUS), cardioembolic stroke due to atrial fibrillation (AF), large-artery atherosclerosis, or small vessel disease. In cohort 2, patients with cryptogenic stroke and patent foramen ovale (PFO) scheduled for PFO closure ( = 38) were enrolled. As measures of vascular risk factor burden, the CHADSVASC score, the Essen Stroke Risk Score (ESRS), and the Risk of Paradoxical Embolism (RoPE) score were calculated, as appropriate.
ADAMTS-13 activity was lower in patients with AF-related stroke compared to patients with ESUS ( = 0.0227), which was, however, due to confounding by vascular risk factors. ADAMTS-13 activity inversely correlated with the ESRS ( = -0.452, < 0.001) and CHADSVASC ( = -0.375, < 0.001) in cohort 1. In accordance with these findings, we found a positive correlation between ADAMTS-13 activity and the RoPE score in cohort 2 ( = 0.413, = 0.010).
ADAMTS-13 activity is inversely correlated with the number of vascular risk factors across different stroke etiologies. Further study is warranted to establish ADAMTS-13 as a mediator of cerebrovascular risk.
确定缺血性中风的潜在机制对二级预防具有重要意义。含血小板反应蛋白基序的解聚素样金属蛋白酶13(ADAMTS - 13)具有抗血栓特性,且多次被认为与中风的病理生理学有关。因此,在本研究中,我们旨在调查ADAMTS - 13是否与中风病因及血管危险因素负担相关。
我们在两个前瞻性招募的中风队列中,于事件发生后的长期病程中测定了ADAMTS - 13活性。队列1(n = 88)由因不明来源栓塞性中风(ESUS)、心房颤动(AF)所致的心源性栓塞性中风、大动脉粥样硬化或小血管疾病而中风的患者组成。在队列2中,纳入了计划进行卵圆孔未闭(PFO)封堵的不明原因中风且卵圆孔未闭的患者(n = 38)。酌情计算CHADSVASC评分、埃森中风风险评分(ESRS)和反常栓塞风险(RoPE)评分,作为血管危险因素负担的衡量指标。
与ESUS患者相比,AF相关性中风患者的ADAMTS - 13活性较低(P = 0.0227),然而,这是由于血管危险因素的混杂作用所致。在队列1中,ADAMTS - 13活性与ESRS呈负相关(r = -0.452,P < 0.001),与CHADSVASC呈负相关(r = -0.375,P < 0.001)。与这些发现一致,我们在队列2中发现ADAMTS - 13活性与RoPE评分呈正相关(r = 0.413,P = 0.010)。
ADAMTS - 13活性与不同中风病因的血管危险因素数量呈负相关。有必要进一步研究将ADAMTS - 13确立为脑血管风险的介质。