ADAMTS-13 activity in stroke of known and unknown cause: Relation to vascular risk factor burden

Gerrit M Grosse; Andrei Leotescu; Jan-Thorben Sieweke; Sonja Schneppenheim; Ulrich Budde; Nora L Ziegler; Saskia Biber; Maria M Gabriel; Johanna Ernst; Ramona Schuppner; Ralf Lichtinghagen; Udo Bavendiek; Julian Widder; Karin Weissenborn

doi:10.3389/fneur.2022.1045478

ADAMTS-13 activity in stroke of known and unknown cause: Relation to vascular risk factor burden

Front Neurol. 2023 Jan 10:13:1045478. doi: 10.3389/fneur.2022.1045478. eCollection 2022.

Authors

Affiliations

¹ Department of Neurology, Hannover Medical School, Hannover, Germany.
² Department of Cardiology, Hannover Medical School, Hannover, Germany.
³ Medilys Laboratory, Asklepios Klinik Altona, Hamburg, Germany.
⁴ Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany.
⁵ Medizinische Klinik VI, Kardiologie, Angiologie und Internistische Intensivmedizin, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.

Abstract

Background: 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.

Methods: We determined ADAMTS-13 activity in two prospectively recruited stroke cohorts in the long-term course after the event. Cohort 1 (n = 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 (n = 38) were enrolled. As measures of vascular risk factor burden, the CHA₂DS₂VASC score, the Essen Stroke Risk Score (ESRS), and the Risk of Paradoxical Embolism (RoPE) score were calculated, as appropriate.

Results: ADAMTS-13 activity was lower in patients with AF-related stroke compared to patients with ESUS (p = 0.0227), which was, however, due to confounding by vascular risk factors. ADAMTS-13 activity inversely correlated with the ESRS (r = -0.452, p < 0.001) and CHA₂DS₂VASC (r = -0.375, p < 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 (r = 0.413, p = 0.010).

Conclusion: 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.

Keywords: ADAMTS-13; biomarker; embolic stroke of undetermined source; patent foramen ovale; stroke etiology; thrombosis.

Grants and funding

This study was supported by PRACTIS—Clinician Scientist Program of Hannover Medical School, funded by the German Research Foundation (grant number: DFG, ME 3696/3-1).