Abstract 9118: Inhibition Of Interleukin-1 Activity By Anakinra Improves Endothelial, Coronary And Aortic Function In Patients With CAD And Coexistent Rheumatoid Arthritis By Reducing Apoptosis And Oxidative Stress
Background: Interleukin-1 mediates atherogenesis and coronary vasoreactivity. Anakinra, a human recombinant interleukin-1a receptor antagonist, is used forthe treatment of rheumatoid arthritis (RA) and shows favourable effects onendothelial and arterial function in RA patients. We investigated the effects of anakinra on coronary endothelial and arterial function in CAD patients with coexistent RA.
Methods: Forty patients with chronic CAD and RA were randomized to receive a single injection of anakinra (100mg s.c.) or placebo and after 48 hours the alternative treatment in a double-blind trial and 23 age and sex matched subjects with similar risk factors served as controls. At baseline and 3 hours after treatment we assessed a) coronary flow reserve (CFR) of the LAD using Doppler echocardiography, b) aortic strain (AS), c) flow mediated endothelial dependent dilation of the brachial artery (FMD) by ultrasonography d) soluble Fas, Fas ligand, nitrotyrosine (NT) and protein carbonyls (PC) serum levels. All controls had no clinical history for CAD and a negative for ischaemia treadmill exercise test.
Results: Patients had impaired FMD, CFR and AS compared to controls(p<0.001). At baseline, NT was related with AS and FMD (r=-0.401 andr=-0.386),while Fas and FasL with CFR (r=-0.450 and r=-0.362) (p<0.05). After 3 hours of anakinra treatment, there was an improvement in FMD, CFR and AS compared to placebo, reaching values similar to those in controls (FMD: 5.1±2.3%, vs.13.9±3.5% vs. 8.1±3.6%, p=0.006, CFR: 2.1±0.7 vs. 3.0±1.1 vs.3.4±0.7, p<0.001, AS: 4.4±2.3% vs. 9.6±3.6% vs. 8.0±2.8 %, p=0.003). Furthermore, there were a decrease in NT (median 6.66 vs. 6.15 nM/L), PC (0.131vs. 0.091 nmol/mg protein), Fas (51.8 vs. 49.3 pg/ml) and FasL levels (47.6 vs. 40.95 pg/ml) after anakinra (p<0.05). No significant changes were observed after placebo.
Conclusion: IL-1 inhibition improves endothelial function and consequently, coronary and aortic wall function, probably through reduction of nitrooxidative stress and apoptosis.
- © 2012 by American Heart Association, Inc.