@article{3129295,
    title = "Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra",
    author = "Ikonomidis, I. and Tzortzis, S. and Lekakis, J. and Paraskevaidis, I. and Dasou, P. and Parissis, J. and Nikolaou, M. and Markantonis, S.L. and Katsimbri, P. and Skarantavos, G. and Andreadou, I. and Anastasiou-Nana, M.",
    journal = "Thrombosis and Haemostasis",
    year = "2011",
    volume = "106",
    number = "5",
    pages = "959-967",
    issn = "0340-6245",
    doi = "10.1160/TH11-02-0117",
    keywords = "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",
    abstract = "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."
}