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.


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.


BACKGROUND
http://www.clinicaltrials.gov. Unique identifier: NCT01566201.
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.
Ignatios
I
Ikonomidis
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.).
Stavros
S
Tzortzis
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.).
Ioanna
I
Andreadou
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.).
Ioannis
I
Paraskevaidis
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.).
Chrysoula
C
Katseli
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.).
Pelagia
P
Katsimbri
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.).
George
G
Pavlidis
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.).
John
J
Parissis
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.).
Dimitrios
D
Kremastinos
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.).
Maria
M
Anastasiou-Nana
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.).
John
J
Lekakis
D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006801:Humans; D007267:Injections; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects
D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1
coronary artery disease; interleukin-1; interleukin-1 receptor antagonist protein; oxidative stress