ABSTRACT To optimize the STAF score by incorporating NT‐proBNP and D‐dimer for improved prediction of cardioembolic stroke (CE) and to investigate their synergistic molecular mechanisms. A retrospective study enrolled 371 AIS patients classified by TOAST criteria (CE vs. non‐CE). Clinical, imaging, and biochemical data were used to construct/evaluate a modified STAF. Diagnostic performance was assessed via ROC curves, DeLong's test, IDI, and NRI. In vitro, H9c2 cardiomyocytes under hypoxia were treated with NT‐proBNP/D‐dimer to assess viability, apoptosis, inflammation, and signaling. In vivo, an AF rat model with cerebral embolism received AAV‐mediated interventions (overexpression/knockdown). The modified STAF incorporated NT‐proBNP ≥ 321.5 ng/L and D‐dimer ≥ 0.67 μg/mL, achieving a significantly higher AUC (0.942) than the original STAF (0.846, p < 0.001). In vitro, NT‐proBNP and D‐dimer synergistically increased apoptosis and inflammation in cardiomyocytes by activating NF‐κB. In vivo, overexpression exacerbated cerebral infarct size and upregulated NLRP3 pathway proteins, while knockdown mitigated these injuries. Incorporating NT‐proBNP and D‐dimer significantly enhances STAF accuracy for CE prediction. These biomarkers synergistically promote cardioembolic inflammation and injury via NF‐κB‐NLRP3 pathway activation, suggesting potential therapeutic targets.
Lin et al. (Mon,) studied this question.