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.
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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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