Molecular and Neuroimaging Profile Associated with the Recurrence of Different Types of Strokes: Contribution from Real-World Data

<b>Objective:</b> This study aimed to investigate potential specific molecular and neuroimaging biomarkers for stroke subtype recurrence to improve secondary stroke prevention. <b>Methods:</b> A retrospective analysis was conducted on a prospective stroke biobank. The main endpoint was to evaluate the association between different biomarkers and the recurrence of stroke subtypes. Serum levels of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-a) were analyzed as inflammation biomarkers; N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and microalbuminuria were used as atrial/endothelial dysfunction biomarkers, while leukoaraiosis (LA) and soluble TNF-like inducers of apoptosis (sTWEAK) were used as biomarkers for blood-brain barrier dysfunction. Demographic and clinical variables were also included. <b>Results:</b> A total of 5038 stroke patients were included, with a mean follow-up of 4.9 years (±3.3). Stroke recurrences were observed in 18.4% of patients (927 individuals). The main results found were as follows: LA was independently associated with lacunar stroke recurrence (adjusted OR 9.50; 95% CI: 3.12-28.93). NT-pro-BNP levels higher than >1000 pg/mL were independently associated with cardioembolic stroke recurrence (adjusted OR 1.80; 95% CI: 1.23-2.61). Persistently elevated TNF-a levels (>24 pg/mL) after stroke recurrence showed an adjusted OR of 21.26 (95% CI: 12.42-37.59) for atherothrombotic subtype, whereas persistently high sTWEAK levels (>7000 pg/mL) after a second hemorrhagic stroke showed an adjusted OR of 4.81 (95% CI: 2.86-8.07) for hemorrhagic subtype. <b>Conclusions:</b> The presence of LA and high levels of NT-pro-BNP, TNF-a, and sTWEAK were associated with an increased risk for lacunar, cardioembolic, atherothrombotic, and hemorrhagic stroke recurrences, respectively.