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

Abstract

BackgroundThe 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.MethodsWe 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.ResultsADAMTS-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).ConclusionADAMTS-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.

Metalloproteinases between History, Health, Disease, and the Complex Dimension of Social Determinants of Health

“…Moreover, ADAMTS-13 is considered an important factor related to several diseases characterized by vascular inflammation and thrombosis, such as cancer, vascular diseases, infections, neurological diseases, and liver diseases [62]. Furthermore, low ADAMTS-13 levels seem to increase the risk of ischemic stroke [61,63]. Several members of this family are also pivotal in the development of the heart and vessels.…”

“…Several members of this family are also pivotal in the development of the heart and vessels. In particular, ADAMTS-7 is related to coronary artery disease (CAD) and may represent a potential therapeutic target, and ADAMTS-9 and ADAMTS-19 are associated with heart valve disease [63]. ADAMTS-1, ADAMTS-4, and ADAMTS-7 are also involved in chronic venous disease (CVD) [3].…”