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

Heart. 2009 Sep;95(18):1502-7. doi: 10.1136/hrt.2009.168971. Epub 2009 May 28.

Abstract

Objective: Inhibition of interleukin-1 activity improves nitro-oxidative stress, endothelial and coronary function. The authors investigated (a) the association of nitro-oxidative stress and endothelial function with myocardial deformation, (b) the effects of anakinra, an interleukin-1a receptor antagonist on myocardial deformation in patients with rheumatoid arthritis (RA).

Methods: The authors compared 46 RA patients to 23 normal controls. 23 patients received anakinra (150 mg subcutaneously once daily) and 23 patients a 5-mg increase of prednisolone dose for 30 days. At baseline and post-treatment this study assessed (a) the left ventricular (LV) longitudinal, circumferential and radial strain and strain rate, using speckle tracking echocardiography, (b) the coronary flow reserve (CFR), (c) the flow-mediated endothelial-dependent dilation of the brachial artery (FMD) and (d) nitrotyrosine (NT) and malondialdehyde blood levels.

Results: Patients had impaired baseline myocardial deformation indices compared to controls (p<0.05). CFR and NT levels were related to longitudinal strain, systolic and diastolic strain rate, circumferential strain and systolic strain rate (p<0.05). FMD was related to longitudinal and circumferential diastolic strain rate (p<0.01). Compared to baseline, anakinra-treated patients increased the longitudinal strain (-17.8% (3.7%) vs -22.1% (3.5%)), systolic (-1.02 (0.23) l/s vs -1.25 (0.23) l/s) and diastolic (0.96 (0.37) l/s vs 1.20 (0.39) l/s) longitudinal strain rate, circumferential strain and strain rate (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients

Conclusions: 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.

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Blood Flow Velocity / drug effects
  • Brachial Artery / physiology
  • Coronary Circulation / drug effects
  • Echocardiography
  • Female
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Interleukin-1 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Myocardium
  • Oxidative Stress / drug effects*
  • Vasodilation / drug effects
  • Ventricular Dysfunction, Left / drug therapy*

Substances

  • Antirheumatic Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1