TY - JOUR
TI - Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra
AU - Ikonomidis, I.
AU - Tzortzis, S.
AU - Lekakis, J.
AU - Paraskevaidis, I.
AU - Dasou, P.
AU - Parissis, J.
AU - Nikolaou, M.
AU - Markantonis, S.L.
AU - Katsimbri, P.
AU - Skarantavos, G.
AU - Andreadou, I.
AU - Anastasiou-Nana, M.
JO - Thrombosis and Haemostasis
PY - 2011
VL - 106
TODO - 5
SP - 959-967
PB - 
SN - 0340-6245
TODO - 10.1160/TH11-02-0117
TODO - antidiabetic agent;  beta adrenergic receptor blocking agent;  calcium channel blocking agent;  caspase 9;  dipeptidyl carboxypeptidase inhibitor;  diuretic agent;  Fas antigen;  Fas ligand;  hydroxymethylglutaryl coenzyme A reductase inhibitor;  interleukin 1beta;  leflunomide;  methotrexate;  nonsteroid antiinflammatory agent;  placebo;  prednisolone;  recombinant interleukin 1 receptor blocking agent;  tumor necrosis factor alpha, adult;  apoptosis;  article;  clinical article;  controlled study;  crossover procedure;  disease association;  disease marker;  double blind procedure;  female;  heart disease;  heart left ventricle impairment;  heart performance;  heart stress;  human;  male;  priority journal;  protein function;  protein modification;  randomized controlled trial;  rheumatoid arthritis;  single drug dose;  tissue Doppler imaging;  treatment duration;  treatment response;  two dimensional echocardiography, Adrenal Cortex Hormones;  Adult;  Aged;  Analysis of Variance;  Antigens, CD95;  Antirheumatic Agents;  Apoptosis;  Arthritis, Rheumatoid;  Biological Markers;  Caspase 9;  Cross-Over Studies;  Double-Blind Method;  Echocardiography, Doppler;  Fas Ligand Protein;  Female;  Greece;  Humans;  Inflammation Mediators;  Interleukin 1 Receptor Antagonist Protein;  Interleukin-1beta;  Logistic Models;  Male;  Middle Aged;  Myocardium;  Prednisolone;  Receptors, Interleukin-1;  Time Factors;  Treatment Outcome;  Tumor Necrosis Factor-alpha;  Ventricular Dysfunction, Left;  Ventricular Function, Left
TODO - Myocardial function is impaired in rheumatoid arthritis (RA). Inhibition of interleukin (IL)-1 activity reduces experimental myocardial infarction by limiting apoptosis. We investigated whether a) soluble apoptotic markers are related with impaired left ventricular (LV) performance and b) treatment with anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to improved LV performance in RA. We studied 46 RA patients. In an acute, double-blind cross-over trial, 23 patients were randomised to a single injection of anakinra or placebo and after 48 hours (h) to the alternative treatment. In a chronic trial, 23 patients who received anakinra for 30 days were compared with 23 patients who received prednisolone. At baseline, 3 h and 30 days after treatment, we measured circulating IL-1β, tumour necrosis factor (TNF)-α, Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using 2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05). After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs. 364 vs. 301 pg/ml), Fasligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9 (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-α and IL-1β (p<0.05 for all comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and their percent changes were related with the corresponding changes of Fas and caspase-9 (p<0.05). No changes of the examined parameters were observed after prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces apoptotic markers leading to improved LV performance in RA. © Schattauer 2011.
ER -