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


CONCLUSIONS
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.
Gonzalez-Juanatey
Carlos
C
Division of Cardiology, Hospital Xeral-Calde, Dr. Ochoa s/n, 27004 Lugo, Spain.
Testa
Ana
A
Garcia-Castelo
Alberto
A
Garcia-Porrua
Carlos
C
Llorca
Javier
J
Vidan
Juan
J
Hajeer
Ali H
AH
Ollier
William E
WE
Mattey
Derek L
DL
Gonzalez-Gay
Miguel A
MA
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D014664:Vasodilation
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains