Interleukin 17 as a novel predictor of vascular function in rheumatoid arthritis

Background Rheumatoid arthritis (RA) is associated with enhanced cardiovascular (CV) risk and subclinical vascular disease. The proinflammatory milieu has been linked to premature atherosclerosis and endothelial dysfunction in RA. While interleukin 17 (IL-17) is considered pathogenic in RA, its role in determining vascular dysfunction in this disease has not been systematically assessed. Objectives To analyse candidate variables that might determine endothelial function in various vascular territories in a cohort of patients with RA receiving treatment with biological agents, with minimal traditional CV risk factors and low disease activity score. Methods Patients with RA (n=50) receiving stable treatment with biological agents underwent measurement of conduit artery endothelial function by brachial artery flow-mediated dilatation; arterial compliance by pulse wave velocity (PWV) assessment; and endothelium-dependent microvascular testing with Endo-Pat2000 device to assess the reactive hyperaemia index (RHI). IL-17 was quantified by ELISA and disease activity was assessed by 28-joint count Disease Activity Score. Results IL-17 was the main determinant of lower RHI in univariate and multivariate analysis. Traditional and non-traditional CV risk variables determined PWV, with a significant positive association with IL-17 in univariate and multivariate analysis. In contrast, conduit endothelial function was mainly determined by rheumatoid factor titres in univariate and multivariate analysis. Anti-cyclic citrullinated peptide titres, specific disease-modifying antirheumatic drugs or biological agents and disease activity did not determine vascular function. Conclusion In patients with RA treated with biological agents, IL-17 is a main predictor of microvascular function and arterial compliance. This study suggests that IL-17 may play a significant role in development of endothelial dysfunction and cardiovascular disease in RA.