Rheumatoid arthritis and accelerated atherogenesis.

To the Editor: In their outstanding review, Sattar et al1 discussed the association between rheumatoid arthritis (RA) and accelerated atherogenesis mediated by systemic inflammatory response. We have recently described severe subclinical atherosclerotic findings in long-term actively treated RA patients (n 47) without clinically evident atherosclerosis or its complications.2 Sattar et al1 underlined the importance of endothelial dysfunction as an initial step in the development of atherogenesis. We also observed that long-term actively treated RA patients (n 55) exhibited a decreased endothelium-dependent vasodilatation (EDV) (mean SD, 3.8 4.9%) compared with matched controls (8.0 4.5%).3 Sattar et al1 also emphasized the importance of proinflammatory cytokines in the development of atherosclerosis in RA patients. Swiss investigators confirmed that tumor necrosis factor (TNF)– blockade improved endothelial function in short-term– treated RA patients.4 We have recently assessed whether anti– TNFtherapy was still effective in improving endothelial function in long-term anti–TNF–treated RA patients.5 We assessed this issue in 7 RA patients who had been treated with anti–TNFmonoclonal antibody (infliximab) for at least 1 year and were receiving periodic treatment (every 8 weeks) with this drug.5 After infliximab infusion, we found a dramatic and rapid increase in the percentage of EDV.5 In all patients, values of percentage of EDV at day 2 after infusion (9.4 5.5%) were greater than those observed 2 days before infusion (2.8 2.5%). However, they returned to baseline by 4 weeks after drug infusion. This new observation highlights the importance of TNFin the mechanisms of atherosclerosis mediated by endothelial dysfunction in RA. Finally, an important issue to be considered is the potential role of genetic factors in the development of atherosclerosis in RA patients. We assessed the influence of HLA-DRB1 status in the development of endothelial dysfunction in our series of 55 long-term actively treated RA patients.3 The percentage of EDV in all 7 HLA-DRB1*0404 patients was 3%. In contrast, only 22 of the 48 HLA-DRB1*0404–negative patients had a percentage of EDV 3%.3 These findings suggest that genetic factors may also be implicated in the development of atherosclerosis in RA. The search for genetic markers associated with the development of atherosclerosis in RA and the use of drugs that may delay the progression of accelerated atherogenesis in RA constitute important issues to be addressed in the near future.