Increased Benefit of Interleukin-1 Inhibition on Vascular Function, Myocardial Deformation, and Twisting in Patients With Coronary Artery Disease and Coexisting Rheumatoid Arthritis

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Abstract
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-1β, nitrotyrosine, malondialdehyde, protein carbonyl, and Fas/Fas ligand levels. At baseline, patients with CAD had 3-fold higher interleukin-1β, protein carbonyl, higher nitrotyrosine, malondialdehyde, and Fas/Fas ligand than non-CAD (PP<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.Clinical Trial Registration—: URL:http://www.clinicaltrials.gov. Unique identifier: NCT01566201.

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