Inflammatory-hemodynamic interplay in severe intracranial stenosis: hs-CRP, vertebral artery flow, and posterior circulation infarction.

BACKGROUND

While systemic inflammation (hs-CRP) is linked to intracranial atherosclerosis, how it precisely translates into focal posterior circulation infarction (PCI) remains elusive. Previous studies largely treat inflammation and hemodynamics as isolated risk factors, leaving their potential synergistic mechanisms unquantified. We hypothesized that vertebral artery volume flow (VAVF) may partly account for the observed association between hs-CRP and PCI, thereby exploring a potential inflammatory-hemodynamic interaction in severe intracranial vertebral artery stenosis (IVAS).

METHODS

This retrospective cohort study included 253 consecutive patients with newly diagnosed severe IVAS. We assessed baseline hs-CRP, VAVF, and incident PCI using generalized additive models, exploratory mediation analysis, and network analyses.

RESULTS

During follow-up, 96 patients (37.9%) developed PCI. Each 1-mg/L increase in hs-CRP was associated with higher odds of PCI (adjusted OR, 1.26; 95% CI, 1.15-1.38; p < 0.001). The association was nonlinear, with an inflection point at 5.67 mg/L and a plateau above 13.28 mg/L. Network analysis identified hs-CRP as a central node within the biomarker network. Exploratory mediation analysis suggested that VAVF partly accounted for the association, with an estimated proportion mediated of 13.2% (p = 0.002). The association was strongest in the lowest VAVF tertile.

CONCLUSION

Our findings support a potential inflammatory-hemodynamic interaction where systemic inflammation is associated with impaired local perfusion and increased risk of PCI. Identification of this "low-flow, high-inflammation" phenotype may provide a framework for future risk stratification and prospective evaluation of inflammation-targeted strategies.