Effects of long-term disease-modifying antirheumatic drugs on endothelial function in patients with early rheumatoid arthritis

Cardiovasc Ther. 2010 Oct;28(5):e53-64. doi: 10.1111/j.1755-5922.2009.00119.x.


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.

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / therapeutic use*
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Biomarkers / blood
  • Carotid Artery, Common / diagnostic imaging
  • Carotid Artery, Common / drug effects
  • Case-Control Studies
  • Coronary Circulation / drug effects
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiopathology
  • Echocardiography, Doppler
  • Endothelium, Vascular / diagnostic imaging
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Italy
  • Male
  • Methotrexate / therapeutic use*
  • Microcirculation / drug effects
  • Middle Aged
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Biomarkers
  • N,N-dimethylarginine
  • Arginine
  • Adalimumab
  • Methotrexate