Endothelial cell dysfunction in RA: biomarkers IL-8, E-selectin, VCAM-1 and MCP-1 correlated with PET/CT.

Objectives: Cardiovascular risk in RA is multifactorial, with endothelial dysfunction being a significant, but not exclusive contributor. This risk is further worsened by accelerated atherosclerosis, increased arterial stiffness, and other inflammation-associated pathophysiological mechanisms, alongside traditional cardiovascular risk factors. This study evaluated the effects of 6 months of anti-inflammatory therapy on endothelial biomarkers, including E-selectin, vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and IL-8. Additionally, correlations between changes in biomarker concentrations and FDG-PET/CT arterial uptake were examined.

Methods: Patients with active RA receiving anti-inflammatory therapy were compared with age- and sex-matched controls with OA. Endothelial biomarkers were measured at baseline, 6 months and 48 months of treatment. FDG-PET/CT was performed at baseline and 6 months after anti-inflammatory treatment to assess arterial inflammation, quantified as the maximal standard uptake value (SUVmax) in the aorta. The longitudinal impact of therapy was assessed across the RA cohort, with additional stratification by disease duration and treatment response.

Results: Final assessment included 40 RA patients (18 early RA, 22 established RA) and 19 OA controls. In the RA cohort, E-selectin (Δ6M-BL= -4 ng/ml ± 3.17; P = 0.006) and IL-8 (Δ6M-BL= -10 pg/ml ± 4.2; P< 0.001) significantly decreased over 6 months. IL-8 decreased in both early (Δ6M-BL= -8 pg/ml ± 4.16; P = 0.022) and established RA (Δ6M-BL= -12 pg/ml ± 4.17; P = 0.004), while E-selectin decreased only in established RA (Δ6M-BL= -5 ng/ml ± 5.22; P = 0.012). Responders to therapy showed reductions in both endothelial markers. PET/CT analysis revealed positive correlations between ΔSUVmax and ΔIL-8, as well as ΔE-selectin.

Conclusion: Anti-inflammatory therapy in RA gives early and sustained reductions in endothelial biomarkers, particularly E-selectin and IL-8, with significant differences across subgroups defined by disease activity and therapeutic responses, and provide significant correlations with aortic regions by FDG PET/CT. These findings highlight a potential therapeutic benefit in reducing cardiovascular risk in patients with RA.