Angiotensin-Converting Enzyme Inhibition Improves Vascular Function in Rheumatoid Arthritis

• Published in: Circulation (New York, N.Y.) Vol. 117; no. 17; pp. 2262 - 2269
• Main Authors: FLAMMER, Andreas J, SUDANO, Isabella, NUSSBERGER, Juerg, LUSCHER, Thomas F, CORTI, Roberto, NOLL, Georg, RUSCHITZKA, Frank, HERMANN, Frank, GAY, Steffen, FORSTER, Adrian, NEIDHART, Michel, KÜNZLER, Peter, ENSELEIT, Frank, PERIAT, Daniel, HERMANN, Matthias
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 29.04.2008
• Subjects: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - epidemiology; Atherosclerosis (general aspects, experimental research); Atherosclerosis - epidemiology; Atherosclerosis - prevention & control; Biological and medical sciences; Biomarkers; Blood and lymphatic vessels; Cardiology. Vascular system; Cells, Cultured; Cross-Over Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - physiology; Female; Humans; Male; Medical sciences; Middle Aged; Oligonucleotide Array Sequence Analysis; Oxidative Stress - drug effects; Ramipril - administration & dosage; Renin-Angiotensin System - drug effects; Risk Factors; Treatment Outcome; Umbilical Veins - cytology; Vasculitis - epidemiology; Vasculitis - prevention & control; Vasodilation - drug effects; Immunopathology; angiotensin-converting enzyme inhibitors; Diseases of the osteoarticular system; Autoimmune disease; Cardiovascular disease; Inflammatory joint disease; Inflammation; Endothelium; Renin angiotensin system; Chronic; arthritis, rheumatoid; Rheumatoid arthritis; Angiotensin; ACE inhibitor
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.107.734384

The excess in cardiovascular risk in patients with rheumatoid arthritis provides a strong rationale for early therapeutical interventions. In view of the similarities between atherosclerosis and rheumatoid arthritis and the proven benefit of angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease, it was the aim of the present study to delineate the impact of ramipril on endothelial function as well as on markers of inflammation and oxidative stress in patients with rheumatoid arthritis. Eleven patients with rheumatoid arthritis were included in this randomized, double-blind, crossover study to receive ramipril in an uptitration design (2.5 to 10 mg) for 8 weeks followed by placebo, or vice versa, on top of standard antiinflammatory therapy. Endothelial function assessed by flow-mediated dilation of the brachial artery, markers of inflammation and oxidative stress, and disease activity were investigated at baseline and after each treatment period. Endothelial function assessed by flow-mediated dilation increased from 2.85+/-1.49% to 4.00+/-1.81% (P=0.017) after 8 weeks of therapy with ramipril but did not change with placebo (from 2.85+/-1.49% to 2.84+/-2.47%; P=0.88). Although systolic blood pressure and heart rate remained unaltered, diastolic blood pressure decreased slightly from 78+/-7 to 74+/-6 mm Hg (P=0.03). Tumor necrosis factor-alpha showed a significant inverse correlation with flow-mediated dilation (r=-0.408, P=0.02), and CD40 significantly decreased after ramipril therapy (P=0.049). Angiotensin-converting enzyme inhibition with 10 mg/d ramipril for 8 weeks on top of current antiinflammatory treatment markedly improved endothelial function in patients with rheumatoid arthritis. This finding suggests that angiotensin-converting enzyme inhibition may provide a novel strategy to prevent cardiovascular events in these patients.