ABSTRACT NUMBER: ESOC2026A356 HIGH-THROUGHPUT PROTEOMICS IDENTIFIES ETIOLOGY-SPECIFIC MOLECULAR SIGNATURES OF STROKE RECURRENCE—INSIGHTS FROM THE CRESCENDO CONSORTIUM

Abstract Background and aims Despite advances in stroke treatment, recurrence risk remains largely unchanged over two decades. In the multicenter CiRculating mEdiators of Stroke reCurrENce anD aetiOlogies (CRESCENDO) consortium, we conducted the first large-scale proteomic analysis of 5,400 targets to characterize post-stroke blood-based proteomic signatures associated with 90-day recurrence. Methods CRESCENDO compiled comprehensive prospective cohorts from Hannover (Germany), Barcelona/Seville (Spain), and Zurich/Basel (Switzerland), comprising 4,854 patients sampled within 24 hours of ischemic stroke. A subset of 175 patients (75 recurrent, 100 non-recurrent), balanced for age, sex, NIHSS, was profiled using the Olink Explore HT panel. Protein levels were compared between recurrent and nonrecurrent cases, and their predictive values were evaluated. Results Across all etiologies, G kinase anchoring protein-1 (GKAP1) was elevated in recurrent cases (logFC = 0.72, adjusted P = 0.02). Etiology-stratified analyses revealed upregulation of Carboxylesterase 1 (CES1) in patients with atherosclerotic index stroke and recurrence (logFC = 1.19, adjusted P = 0.02), and enrichment of Centromere Protein F (CENPF), Biliverdin Reductase B (BLVRB), and Parkinson disease protein 7 (PARK7) patients with cardioembolic index stroke and recurrence (logFC = 1.13, 0.99, 0.98, adjusted P = 0.02, 0.03, 0.04). Recurrence prediction using clinical data alone had an accuracy of 0.55, which increased to 0.61 when etiology-specific proteins were added. Conclusions High-throughput proteomics identified novel, etiology-specific proteins associated with 90-day recurrence. The improvement in predictive accuracy when integrating these markers suggests that etiology-stratified proteomic profiling can uncover distinct biological drivers of recurrence, warranting larger studies to refine targeted secondary prevention. Conflict of interest nothing to disclose.