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.
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), Fas-ligand (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.
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Athens, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Ikonomidis
authors.forename: S
authors.initials: S
authors.lastname: Tzortzis
authors.forename: J
authors.initials: J
authors.lastname: Lekakis
authors.forename: I
authors.initials: I
authors.lastname: Paraskevaidis
authors.forename: P
authors.initials: P
authors.lastname: Dasou
authors.forename: J
authors.initials: J
authors.lastname: Parissis
authors.forename: M
authors.initials: M
authors.lastname: Nikolaou
authors.forename: S L
authors.initials: SL
authors.lastname: Markantonis
authors.forename: P
authors.initials: P
authors.lastname: Katsimbri
authors.forename: G
authors.initials: G
authors.lastname: Skarantavos
authors.forename: I
authors.initials: I
authors.lastname: Andreadou
authors.forename: M
authors.initials: M
authors.lastname: Anastasiou-Nana
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D053453:Caspase 9 / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D006115:Greece; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D011239:Prednisolone / Q000627:therapeutic use; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*; D019014:fas Receptor / Q000097:blood
chemical_list: D000305:Adrenal Cortex Hormones; D018501:Antirheumatic Agents; D015415:Biomarkers; C491901:FAS protein, human; D053222:Fas Ligand Protein; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D011239:Prednisolone; C506433:CASP9 protein, human; D053453:Caspase 9