HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis

Am J Med. 2003 Jun 1;114(8):647-52. doi: 10.1016/s0002-9343(03)00133-5.


Purpose: To examine endothelial function in rheumatoid arthritis patients and to assess whether clinical or genetic factors affect the development of endothelial dysfunction.

Methods: Fifty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with one or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, or cardiovascular disease were excluded. Thirty-one age-, sex-, and ethnically matched controls were also studied. Endothelium-dependent (postischemia) and -independent (postnitroglycerin) vasodilatation were measured by brachial ultrasonography. Patients were genotyped for human leukocyte antigen (HLA)-DRB1.

Results: Patients had decreased endothelium-dependent vasodilatation (mean [+/- SD], 3.8% +/- 4.9%) compared with controls (8.0% +/- 4.5%; P <0.001). There were no differences in endothelium-independent vasodilatation. Clinical features were not associated with endothelial dysfunction. Endothelium-dependent vasodilatation was lower in the 30 rheumatoid arthritis patients with the HLA-DRB1*04 shared epitope alleles (2.4% +/- 4.1%) than in the remaining patients (5.5% +/- 5.3%; P = 0.01). Similar results were seen for patients with the HLA-DRB1*0404 shared epitope allele (-0.4% +/- 2.5%) compared with other patients (4.4% +/- 4.9%; P = 0.01).

Conclusion: Patients with chronically treated rheumatoid arthritis had evidence of endothelial dysfunction, especially those with certain HLA-DRB1 genotypes. If confirmed, our results suggest that HLA-DRB1 status may be a predictor of cardiovascular risk in these patients.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / physiopathology*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Genetic Predisposition to Disease
  • HLA-DR Antigens*
  • HLA-DRB1 Chains
  • Histocompatibility Testing
  • Humans
  • Male
  • Middle Aged
  • Vasodilation


  • HLA-DR Antigens
  • HLA-DRB1 Chains