Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis

Ikonomidis, Ignatios; Tzortzis, Stavros; Lekakis, John; Paraskevaidis, Ioannis; Andreadou, Ioanna; Nikolaou, Maria; Kaplanoglou, T.; Katsimbri, Pelagia; Skarantavos, G.; Soucacos, P.N.; Kremastinos, Dimitrios Th.

doi:10.1136/hrt.2009.168971

Cited by 84 publications

(70 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we extent our previous findings 4,5 in a novel cohort of patients with CAD and we report for the first time a greater improvement in LV twisting and untwisting properties associated with improved LVEF 3 hours after anakinra treatment in CAD compared with non-CAD patients.…”

Section: Effects Of Il-1 Inhibition On LV Function In Cad Versus Non-cadsupporting

confidence: 51%

“…[4][5][6] In the present study, we have shown that circulating IL-1β levels in RA patients with CAD were 3-fold higher compared with those without CAD and similar RA disease activity. This finding suggests that the inflammatory and atherogenic processes characterizing RA and CAD have an additive effect on IL-1 production.…”

Section: Baseline Differences Between Ra Patients With and Without Cadmentioning

confidence: 63%

“…Longitudinal myocardial deformation is impaired in both patients with CAD and RA 4,5,11 and has an independent prognostic value in CAD. 11 Furthermore, LV twisting and untwisting are major determinants of LV performance 9 and may define LV remodeling after acute myocardial infarction.…”

Section: Effects Of Il-1 Inhibition On LV Function In Cad Versus Non-cadmentioning

confidence: 99%

“…4,5,16,25 In particular, the rapid improvement of LV myocardial deformation, twisting, and untwisting observed in the present study may be explained by (1) rapid inhibition of nuclear factor-κB, inducible nitric oxide synthase, and interleukin-6 22,25,26 combined with a concomitant increase in endothelial nitric oxide synthase, as confirmed by an improved FMD 23,24 ; (2) reduction of peroxynitrate, lipid, and protein peroxidation, as assessed by reduction of nitrotyrosine, malondialdehyde, and PC, respectively [15][16][17]27 ; (3) improved mitochondrial function 21 after inhibition of IL-1 activity by anakinra; and (4) improved coronary microcirculatory function as assessed by CFR and arterial wall elastic properties as assessed by systemic arterial compliance and resistance. However, this improvement was more evident in the patients with CAD compared with their non-CAD counterparts likely because of the 3-fold higher levels of IL-1β and the 2-fold greater oxidative burden observed in CAD than in non-CAD patients at baseline.…”

Section: Effects Of Il-1 Inhibition On LV Function In Cad Versus Non-cadmentioning

confidence: 99%

“…Subsequently, we calculated the average global longitudinal strain (LongS) and longitudinal strain rate (LongSR) from the apical views as well as the global circumferential strain (CircS) and strain rate (CircSR) from the midventricular short-axis view according to previously published methodology. 4 LongS and LongSR values for each one of the 17 LV segments were noted.…”

Section: Two-dimensional Strain Measurementsmentioning

confidence: 99%

See 4 more Smart Citations

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

Ikonomidis

Tzortzis

Andreadou

et al. 2014

Circ: Cardiovascular Imaging

140

119

View full text Add to dashboard Cite

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.

show abstract

Section: Effects Of Il-1 Inhibition On LV Function In Cad Versus Non-cadsupporting

confidence: 51%

Section: Baseline Differences Between Ra Patients With and Without Cadmentioning

confidence: 63%

Section: Effects Of Il-1 Inhibition On LV Function In Cad Versus Non-cadmentioning

confidence: 99%

Section: Effects Of Il-1 Inhibition On LV Function In Cad Versus Non-cadmentioning

confidence: 99%

Section: Two-dimensional Strain Measurementsmentioning

confidence: 99%

See 3 more Smart Citations

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

Ikonomidis

Tzortzis

Andreadou

et al. 2014

Circ: Cardiovascular Imaging

140

119

View full text Add to dashboard Cite

show abstract

Left Ventricular Systolic Myocardial Function in Ankylosing Spondylitis

Midtbø

Semb

Matre

et al. 2019

Arthritis Care & Research

View full text Add to dashboard Cite

Objective. Subclinical left ventricular (LV) myocardial dysfunction is associated with an increased risk of cardiovascular disease (CVD), but it is not known whether subclinical LV myocardial dysfunction is present in patients with ankylosing spondylitis (AS) independent of CVD risk factors.Methods. Conventional and speckle tracking echocardiography were performed in 106 patients with AS (mean ± SD age 48 ± 12 years; 59% men) and 106 matched controls (mean ± SD age 51 ± 12 years; 59% men). LV systolic myocardial function was assessed by peak systolic global longitudinal strain (GLS).Results. CVD risk factors were similarly distributed in patients with AS and controls, but more controls received statin therapy (P = 0.05). GLS was significantly lower in patients with AS compared to controls (mean ± SD −17.7 ± 2.5% versus −18.4 ± 2.3%; P = 0.03). In univariable linear regression analyses in the total study population, lower GLS was associated with having AS, male sex, higher body mass index, higher LV mass index, and lower LV ejection fraction (all P < 0.05). Having AS retained an independent association with lower GLS when adjusted for these factors in multivariable analyses (β = 0.16, P = 0.02). In patients with AS, lower GLS was independently associated with larger aortic root diameter in multivariable analyses (β = 0.24, P = 0.02), while no association with AS disease activity, disease duration, or use of antirheumatic medication was observed.Conclusion. Patients with AS had lower GLS compared with controls, independent of confounders. In AS patients, lower GLS was associated with larger aortic root diameter. Prospective studies should test whether lower GLS contributes to the observed higher CVD risk in patients with AS.

show abstract

Inflammatory markers in coronary artery disease

et al. 2012

View full text Add to dashboard Cite

Coronary artery disease (CAD) is one of the most common manifestations of atherosclerosis. Inflammation is considered one of the major processes that contribute to atherogenesis. Inflammation plays an important role not only on the initiation and progression of atherosclerosis but also on plaque rupture, an event that leads to acute vascular events. Various biomarkers express different pathways and pathophysiologic mechanisms of cardiovascular disease, and inflammatory biomarkers express different parts of the atherogenic process, regarding the initiation and progression of atherosclerosis or the destabilization of the atherosclerotic plaque. Therefore, inflammatory biomarkers may prove to be useful in the detection, staging, and prognosis of patients with CAD. Furthermore, the fact that inflammatory processes are essential steps in the course of the disease offers future therapeutic targets for the interruption of the atherogenic process or for the management of acute events.

show abstract

Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis

Abstract: Myocardial deformation is impaired in RA patients and is related to nitro-oxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitro-oxidative stress.

Cited by 84 publications

References 30 publications

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

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

Left Ventricular Systolic Myocardial Function in Ankylosing Spondylitis

Inflammatory markers in coronary artery disease

Contact Info

Product

Resources

About