Ignatios Ikonomidis1, Stavros Tzortzis2, Ioanna Andreadou2, Ioannis Paraskevaidis2, Chrysoula Katseli2, Pelagia Katsimbri2, George Pavlidis2, John Parissis2, Dimitrios Kremastinos2, Maria Anastasiou-Nana2, John Lekakis2. 1. From the 2nd Cardiology Department (I.I., S.T., I.P., G.P., J.P., D.K., M.A.-N., J.L.) and 4th Department of Internal Medicine, Rheumatology Unit (P.K.), Attikon Hospital, University of Athens, Athens, Greece; and Department of Pharmaceutical Chemistry, University of Athens School of Pharmacy, Athens, Greece (I.A., C.K.). ignoik@otenet.gr. 2. From the 2nd Cardiology Department (I.I., S.T., I.P., G.P., J.P., D.K., M.A.-N., J.L.) and 4th Department of Internal Medicine, Rheumatology Unit (P.K.), Attikon Hospital, University of Athens, Athens, Greece; and Department of Pharmaceutical Chemistry, University of Athens School of Pharmacy, Athens, Greece (I.A., C.K.).
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 (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. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01566201.
RCT Entities:
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 (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 arthritispatients with CAD than in those without. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01566201.
Authors: Gian Luca Erre; Giorgio Buscetta; Panagiotis Paliogiannis; Arduino Aleksander Mangoni; Ciriaco Carru; Giuseppe Passiu; Angelo Zinellu Journal: Rheumatol Int Date: 2018-05-07 Impact factor: 2.631