Deep proteomic profiling of 88 carotid endarterectomy patients (51 symptomatic, 37 asymptomatic) using the Olink Explore 3072 platform identified 19 differentially expressed plaque proteins linked to symptomatic presentation. FGFBP1 showed the strongest association (log2 fold change = 1.14; P = 1.82×10⁻⁶), while neutrophil degranulation, TNF/NF-κB, complement activation, and IL6-JAK-STAT3 pathways dominated vulnerability signatures. Critically, a proteomics-based discrimination model achieved AUC 0.83 versus 0.66 for conventional histopathology — a statistically significant improvement. Plaque-plasma protein concordance was modest overall (median ρ = 0.11), though FGFBP1 showed concordant plasma associations.
This finding matters because histopathology-defined plaque vulnerability — grading lipid cores, fibrous caps, calcification — has long been the clinical standard, yet it notoriously fails to predict which patients will suffer strokes. The proteomic approach here suggests that immune activation state, not just structural architecture, may be the decisive factor in plaque rupture. FGFBP1, a fibroblast growth factor binding protein implicated in angiogenesis and tissue remodeling, emerges as a compelling biomarker candidate. The integration with single-cell RNA-sequencing adds mechanistic granularity rarely seen in plaque studies. However, the cohort of 88 patients is small, the design is cross-sectional and observational, and causality cannot be established. As a preprint posted on medRxiv and not yet peer-reviewed, these results require independent replication before clinical translation. If validated, plasma FGFBP1 measurement could eventually help stratify carotid stenosis patients toward intervention — a genuinely meaningful advance.