Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis.

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.

• Authors: Ignatios Ikonomidis, Stavros Tzortzis, Ioanna Andreadou, Ioannis Paraskevaidis, Chrysoula Katseli, Pelagia Katsimbri, George Pavlidis, John Parissis, Dimitrios Kremastinos, Maria Anastasiou-Nana, John Lekakis
• Journal: Circulation. Cardiovascular imaging (Circ Cardiovasc Imaging) Vol. 7 Issue 4 Pg. 619-28 (Jul 2014) ISSN: 1942-0080 [Electronic] United States
• PMID: 24782115 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Antirheumatic Agents
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1

Topics

• Antirheumatic Agents (administration & dosage)
• Arthritis, Rheumatoid (blood, complications, drug therapy)
• Blood Flow Velocity (drug effects)
• Brachial Artery (drug effects, physiopathology)
• Coronary Artery Disease (complications, drug therapy, physiopathology)
• Coronary Circulation (drug effects)
• Coronary Vessels (drug effects, physiopathology)
• Cross-Over Studies
• Double-Blind Method
• Echocardiography
• Female
• Humans
• Injections
• Interleukin 1 Receptor Antagonist Protein (administration & dosage)
• Interleukin-1 (antagonists & inhibitors, metabolism)
• Male
• Middle Aged
• Treatment Outcome
• Vascular Resistance (drug effects)
• Vasodilation (drug effects, physiology)
• Ventricular Function, Left (drug effects)