Angiotensin-Converting Enzyme Inhibition Improves Vascular Function in Rheumatoid Arthritis

Abstract

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-α 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.

Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis

“…This suggests an acute beneficial effect on HD-induced endothelial cell injury through CF ingestion. Impressively, the degree of reversion of endothelial dysfunction is comparable with the effects observed in ESRD through administration of statins, use of angiotensin-converting enzyme inhibitors in patients with cardiovascular risk, or use of other dietary intervention and lifestyle modification studies (40)(41)(42)(43). The effects on the conduit arteries with improved endothelial functions did not translate into reduced arterial stiffness indices after this 30-day ingestion period.…”

Response to Letter Regarding Article, “Angiotensin-Converting Enzyme Inhibition Improves Vascular Function in Rheumatoid Arthritis”

“…Finally, although we appreciate that Drs Popa and Netea agree with our conclusion that further exploration of angiotensinconverting enzyme inhibitory strategies in rheumatoid arthritis is extremely important, only large-scale prospective randomized clinical trials will provide evidence that the improvements in vascular function with angiotensin-converting enzyme inhibitors, 1 antiinflammatory strategies, 2 and statins 3 translate into a reduction in the cardiovascular burden of our patients with rheumatoid arthritis.…”

Korean rheumatology workforce from 1992 to 2015: current status and future demand

“…In addition to adverse effects related to other biological functions of the primary targets (for example, Jak kinases), off-target effects may also represent a major problem for smallmolecule inhibitors. There are, however, strategies that may predict off-target effects in an early phase of drug development, such as genome-wide transcriptome analysis, other in vitro and in vivo assays or new design of future clinical trials [21][22][23].…”