RESEARCH: Effects of Long‐Term Disease‐Modifying Antirheumatic Drugs on Endothelial Function in Patients with Early Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long‐term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty‐five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS‐28), 2D‐echo derived coronary flow reserve (CFR), common carotid intima‐media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS‐28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P < 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P < 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.

Asymmetric dimethylarginine and arginine levels in patients with rheumatoid arthritis

“…CRP levels correlated with ESR and disease duration. Our results support both Turiel et al [22,30] and Surdacki et al studies [21,31] in terms of the relation between ADMA and inflammation. Surdacki et al displayed that neither ADMA nor SDMA (symmetric dimethylarginine) were correlated with the disease activity and inflammatory activation [21,31].…”

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

“…Moreover, while CIMT and stiffness are relatively stable, vasodilatation can be affected by many confounding factors, such as disease duration and patient age. Furthermore, the majority of our patients were taking immunosuppressive drugs, which have an antiinflammatory effect that potentially affected the atherosclerosis process and, therefore, our results (52,53). The main limitation of this study was the small number of patients; this, in itself, may be due to the low prevalence of SSc (between 3 and 24 cases per 100,000 subjects) (45,46) and the size of our cohort that, however, was similar to the size of other studies.…”

The correlation between cardiovascular risk and functional disability and disease activity in patients with rheumatoid arthritis

“…Twenty-five ERA patients who had not experienced any cardiovascular events were evaluated. It was found that DMARDs significantly decreased DAS-28 scores (from 6.0 ± 0.8 to 2.0 ± 0.7) and increased coronary flow reserve (27). In another study, following a 12-week therapy with infliximab, a TNF-α blocker, a significant decrease of DAS-28 scores and lowered ESR and CRP levels were demonstrated (28,29).…”