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 receptor antagonist, on coronary and left ventricular function in coronary artery disease (CAD) patients with rheumatoid arthritis. Methods and Results-In a double-blind crossover trial, 80 patients with rheumatoid arthritis (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 (1) flow-mediated dilation of brachial artery; (2) coronary flow reserve, ejection fraction, systemic arterial compliance, and resistance by echocardiography; (3) left ventricular global longitudinal and circumferential strain, peak twisting, untwisting velocity by speckle tracking; and (4) interleukin-1 beta, nitrotyrosine, malondialdehyde, protein carbonyl, and Fas/Fas ligand levels. At baseline, patients with CAD had 3-fold higher interleukin-1 beta, protein carbonyl, higher nitrotyrosine, malondialdehyde, and Fas/Fas ligand than non-CAD (P<0.05). After anakinra, there was a greater improvement of flow-mediated dilation (57 +/- 4% versus 47 +/- 5%), coronary flow reserve (37 +/- 4% versus 29 +/- 2%), arterial compliance (20 +/- 18% versus 2 +/- 17%), resistance (-11 +/- 19% versus 9 +/- 21%), longitudinal strain (33 +/- 5% versus 18 +/- 2%), circumferential strain (22 +/- 5% versus 13 +/- 5%), peak twisting (30 +/- 5% versus 12 +/- 5%), untwisting velocity (23 +/- 5% versus 13 +/- 5%), ejection fraction (12 +/- 5% versus 0.5 +/- 5%), apoptotic and oxidative markers, and, in particular, of protein carbonyl (35 +/- 20% versus 14 +/- 9%) in CAD than in non-CAD patients (P<0.01). No changes in the examined markers were observed after placebo. Conclusions-Interleukin-1 inhibition causes a greater improvement in endothelial, coronary aortic function in addition to left ventricular myocardial deformation and twisting in rheumatoid arthritis patients with CAD than in those without.