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(Circulation. 2008;117:2262-2269.)
© 2008 American Heart Association, Inc.

Vascular Medicine

Angiotensin-Converting Enzyme Inhibition Improves Vascular Function in Rheumatoid Arthritis

Andreas J. Flammer, MD^*; Isabella Sudano, MD, PhD^*; Frank Hermann, MD; Steffen Gay, MD; Adrian Forster, MD; Michel Neidhart, PhD; Peter Künzler, MSc; Frank Enseleit, MD; Daniel Périat, MD; Matthias Hermann, MD; Juerg Nussberger, MD; Thomas F. Luscher, MD; Roberto Corti, MD; Georg Noll, MD; Frank Ruschitzka, MD

From the Cardiovascular Centre, Cardiology (A.J.F., I.S., F.H., F.E., D.P., M.H., T.F.L., R.C., G.N., F.R.), and Department of Rheumatology (S.G., A.F., M.N., P.K.), University Hospital Zurich, Zurich; Center for Integrative Human Physiology (S.G., T.F.L., R.C., G.N., F.R.), University of Zurich, Zurich; and Department of Internal Medicine, Division of Angiology and Hypertension (J.N.), University Hospital Lausanne, Lausanne, Switzerland.

Correspondence to Frank Ruschitzka, MD, FESC, FRCP, Cardiology, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland. E-mail frank.ruschitzka{at}usz.ch

Received August 21, 2007; accepted February 8, 2008.

Background— 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.

Methods and Results— 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- 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).

Conclusions— 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.

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