Increased Benefit of Interleukin 1 Inhibition on Vascular Function, Myocardial Deformation, and Twisting in Patients with Coronary Artery Disease and Coexisting Rheumatoid Arthritis
Background—We investigated the effects of anakinra, an interleukin-1 (IL-1) receptor antagonist, on coronary and left ventricular (LV) function in coronary artery disease patients (CAD) with rheumatoid atrhritis (RA).
Methods and Results— In a double-blind cross-over trial, 80 RA patients, (60 with CAD and 20 without) were randomized to a single injection of anakinra or placebo and after 48-hours to the alternative treatment. At baseline and 3 hours after treatment, we assessed a) flow mediated dilation of brachial artery (FMD) b) coronary flow reserve (CFR),ejection fraction (EF), systemic arterial compliance and resistance by echocardiography c) LV Global Longitudinal (LongS) and circumferential (CricS) strain, peak Twisting (Tw), untwisting velocity (UnTwVel) by speckle tracking d)Interleukin-1b (IL-1β), nitrotyrosine (NT), malondialdehyde (MDA), protein carbonyl and Fas, Fas ligand levels. At baseline CAD patients had 3-fold higher IL-1β and protein carbonyl and higher NT, MDA, Fas, Fas ligand than non-CAD (p<0.05). After anakinra, there was a greater improvement of FMD (57±4% vs.47±5%), CFR (37±4% vs.29±2%), arterial compliance (20±18% vs. 2±17%), resistance (-11±19% vs. 9±21%), LongS (33±5% vs.18±2%), CircS (22±5% vs. 13±5%), Tw (30±5% vs. 12±5%), UnTwVel (23±5% vs. 13±5%), EF (12±5% vs. 0.5±5%), apoptotic and oxidative markers and in particular of protein carbonyl (35±20% vs.14±9%) in CAD than in non-CAD patients (p<0.01). No changes in the examined markers were observed after placebo.
Conclusion—IL-1 inhibition causes a greater improvement in endothelial, coronary aortic function in addition to LV myocardial deformation and twisting in RA patients with CAD than in those without.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01566201.
- myocardial deformation
- oxidative stress
- endothelial function
- coronary artery disease
- Received September 16, 2013.
- Accepted April 16, 2014.