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Original article
Anti-inflammatory treatment improves high-density lipoprotein function in rheumatoid arthritis
  1. Francis O'Neill1,
  2. Marietta Charakida1,
  3. Eric Topham2,
  4. Eve McLoughlin1,
  5. Neha Patel1,
  6. Emma Sutill1,
  7. Christopher W M Kay2,
  8. Francesco D'Aiuto3,
  9. Ulf Landmesser4,
  10. Peter C Taylor5,
  11. John Deanfield1,6
  1. 1Vascular Physiology Unit, Institute of Cardiovascular Science, University College London, London, UK
  2. 2Institute of Structural & Molecular Biology and London Centre for Nanotechnology, University College London, London, UK
  3. 3Periodontology Unit, Department of Clinical Research, University College London Eastman Dental Institute, London, UK
  4. 4Department of Cardiology, Charite Universitätsmedizin Berlin, Berlin, Germany
  5. 5Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
  6. 6National Institute for Cardiovascular Outcomes Research, University College London, London, UK
  1. Correspondence to Professor John Deanfield, National Centre for Cardiovascular Prevention and Outcomes (incorporating NICOR), UCL Institute of Cardiovascular Sciences, Nomura House—Level 2 East, 1 St Martin's Le Grand, London EC1A 4NP, UK; j.deanfield{at}ucl.ac.uk

Abstract

Objective Patients with rheumatoid arthritis (RA) are at increased cardiovascular risk. Recent studies suggest that high-density lipoprotein (HDL) may lose its protective vascular phenotype in inflammatory conditions. However, the effects of common anti-inflammatory treatments on HDL function are not yet known.

Methods We compared the function of HDL in 18 patients with RA and 18 matched healthy controls. Subsequently, patients were randomised to (methotrexate+infliximab (M+I) (5 mg/kg)) or methotrexate+placebo (M+P) infusions for 54 weeks. At week 54 and thereafter, all patients received infliximab therapy until completion of the trial (110 weeks), enabling assessment of the impact of 1 year of infliximab therapy in all patients. HDL functional properties were assessed at baseline, 54 weeks and 110 weeks by measuring the impact on endothelial nitric oxide (NO) bioavailability and superoxide production (SO), paraoxonase activity (PON-1) and cholesterol efflux.

Results All HDL vascular assays were impaired in patients compared with controls. After 54 weeks, NO in response to HDL was significantly greater in patients who received M+I compared with those who received M+P. Endothelial SO in response to HDL was reduced in both groups, but PON-1 and cholesterol efflux remained unchanged. All vascular measures improved compared with baseline after ≥1 infliximab therapy in the analysis at 110 weeks. No significant trend was noted for cholesterol efflux.

Conclusions HDL function can be improved with anti-inflammatory treatment in patients with RA. The M+I combination was superior to the M+P alone, suggesting that the tumour necrosis factor-α pathway may have a role in HDL vascular properties.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Preliminary results from this study were presented at the European Society of Cardiology Congress in 2014 (abstract no. 87557).

  • Contributors FON, MC, PC and JD made substantial contributions to the conception and design of the work. FON, EM, NP and ES made substantial contributions to the acquisition, analysis or interpretation of data for the work. FON, MC, CWMK, UL, FD, PCT and JD made substantial contribution to the work or revising it critically for important intellectual content and final approval of the version to be published.

  • Funding F. Hoffmann-La Roche and the Leducq Foundation.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Riverside Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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