PREDICT-EV: Inflammatory Burden Differentiates Transient Ischaemic Attack from Mimics—An Investigation into Inflammatory Markers and Extracellular Vesicle Profiling

Ischaemic stroke is a leading cause of death globally. A transient ischaemic attack (TIA), hallmarked by temporary stroke-like symptoms, is a major warning sign for impending stroke. Identifying high-risk TIA patients is therefore essential. The immunological response post-stroke is complex, given the common co-morbidities with inflammatory signatures in these patients. However, the role of post-TIA inflammation remains poorly understood. The PREDICT-EV study (clinical trial CT/1245/281530/19/20; 30 November 2022) has recruited 180 TIA patients, 30 TIA mimics and 40 healthy controls. Cohort characteristics, inflammatory profiles and the extracellular vesicle (EV) phenotypes were determined. The data presented are a snapshot of the ongoing study, which will monitor participants for progression to stroke over 3 years. TIA patients have significantly higher systolic blood pressure and cumulative risk scores (ABCD 2 and Dawson). Inflammatory markers (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were significantly elevated in TIA patients compared with TIA mimic and healthy controls. EV concentration was equally increased in both TIA mimics and TIA patients. Phenotypic analysis revealed a shift in EV origin; while EVs in healthy controls were predominantly platelet-derived, TIA patients and TIA mimics showed higher proportions of endothelial, red and white blood cell-derived EV. Endothelial activation in TIA patients was confirmed by elevated plasma levels of E-selectin and CD105. These findings suggest a distinct inflammatory and EV phenotype in TIA patients that differentiates them from TIA mimics. The relationship between this profile and future stroke risk will be further explored as the PREDICT-EV study progresses.