FXI levels are related to endothelial function and endothelial activation biomarkers in patients with recent acute coronary syndrome

Background FXI-deficient individuals are protected against cardiovascular (CV) diseases. FXI level has been shown to predict CV events. Aside from its role in the intrinsic coagulation pathway, there is initial evidence linking FXI to inflammation and endothelial permeability. Endothelial function has been widely used as a surrogate physiological biomarker for CV health. Purpose We set out to investigate potential relationships between plasma FXI levels, endothelial activation biomarkers, and endothelial function in patients with recent acute coronary syndrome (ACS). Methods 200 patients with recent ACS undergoing PCI within 4 weeks of the index event were recruited. Each patient made two visits to the research unit: within 4 weeks (V1) and 4 months (V2) after the index event. At each visit, patients underwent extensive examinations including cardiovascular ultrasound, flow-mediated vasodilation, and biomarker assessment. Endothelial activation biomarkers were measured using the Olink Proteomics platform. Flow mediated vasodilation (FMD) was assessed using ultra-high-resolution ultrasound before and after 5 min of forearm occlusion. Results FXI levels are strongly correlated between the two visits (r=0.90, p<0.0001) (Fig 1A), with a slight although significant decline at V2 vs V1 (p<0.0001) (Fig 1B). FXI levels measured within 4 weeks are correlated to MCP-1 (r=0.29, p=0.0001) (Fig 1C), MPO (r=0.36, p<0.0001) (Fig 1D), TIE2 (r=0.41, p<0.0001) (Fig 1E), VEGF-A (r=0.29, p=0.0001) (Fig 1F). Post ACS (V1), there is a significant inverse relationship between FXI level and stroke volume (r=-0.30, p<0.0001). High FXI levels within 4 weeks post ACS are inversely correlated with endothelial function measured by FMD 4 months after the index event (r=-0.27, p=0.007) (Fig 2). FXI level remains the only significant predictor of FMD (p=0.01) following multivariate adjustments for age, gender, diabetes, and hypertension. Conclusions Apart from its role in coagulation, elevated FXI level in the subacute phase post ACS is related to endothelial activation and future endothelial dysfunction. These findings may support the novel therapeutic approach to silence FXI for cardiovascular protection beyond the anti-thrombotic mode of action.