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

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Abstract

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.

Section snippets

Subjects

Patients who fulfilled the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis (12) and who were treated by the same group of rheumatologists were recruited from the Hospital Xeral-Calde, Lugo, Spain. Patients were considered seropositive if a test for rheumatoid factor (by nephelometry) was positive at least twice during the course of the disease. The cohort constituted patients seen at the hospital outpatient clinic during a 1-month period (May 2001).

As the

Results

The patient group comprised 13 men and 42 women, whereas the control group comprised 6 men and 25 women (P = 0.7). The mean (± SD) age at the time of the study was 59.1 ± 12.3 years; the average age in the control group was 58.1 ± 10.7 years (P = 0.7). Serum cholesterol levels were similar in patients (206 ± 34 mg/dL) and controls (208 ± 34 mg/dL; P =0.8).

Discussion

Recent reports confirm an increased incidence of cardiovascular complications in patients with rheumatoid arthritis, perhaps up to fourfold greater than in the general population 17, 18. The increased risk of cardiovascular events was independent of traditional cardiovascular risk factors (18). Thus, the search for other predictors of cardiovascular disease is of great importance; vascular endothelial dysfunction, which is closely linked to the development of atherosclerosis, is one possible

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