Abstract
This article discusses the rationale and design of the study "Methotrexate, blood pressure, and arterial function in rheumatoid arthritis". The recognition that immune activation and excess inflammation favor atherosclerosis has stimulated a significant body of research not only to identify new drugs targeting these pathways but also to repurpose (reposition) existing immunomodulatory medications as atheroprotective agents. Observational studies in patients with rheumatoid arthritis have reported that treatment with methotrexate, a traditional disease-modifying antirheumatic drug, is associated with a significantly lower risk of cardiovascular morbidity and mortality when compared with other disease-modifying antirheumatic drugs. One potential mechanism accounting for the reduced cardiovascular risk associated with methotrexate is the lowering effect on arterial blood pressure. However, such effect has only been observed in cross-sectional and observational studies. Given the established role of hypertension as a leading cardiovascular risk factor, these observations justify an intervention comparison study, the focus of this article, investigating the temporal effects of methotrexate on blood pressure and various surrogate markers of atherosclerosis in patients with rheumatoid arthritis. The results of this study might lead to the repurposing of methotrexate for cardiovascular prevention in patients with and without autoimmune disorders.Clinical Trial Registration: NCT03254589 (ClinicalTrials.gov).