Session Type: Abstract Submissions (ACR)
The mechanism for the increased cardiovascular morbidity and mortality in rheumatoid arthritis (RA) is incompletely understood. In a previous analysis, we found that both the erythrocyte sedimentation rate and the C-reactive protein were associated with the carotid intima-media thickness (IMT) in RA patients, suggesting that systemic inflammation plays a role. Cytokines are important mediators in inflammation and can be measured in the serum. We examined the association between the serum concentration of cytokines/chemokines and the carotid IMT in patients with RA.
We performed a high-resolution carotid ultrasound in patients with RA for measurement of the internal and common carotid IMT, expressed as a composite. A subset of patients returned for a repeat ultrasound of the common carotid IMT, following a protocol designed to assess change. A stored sample of patients’ serum at baseline was used to measure 38 cytokines using a multiplex ELISA technique. We used a multivariable stepwise selection process to identify cytokines associated cross-sectionally with the composite carotid IMT, and with rapid progression of the common carotid IMT.
Results: A baseline scan was performed on 1,162 RA patients, 873 of whom were women. The mean composite carotid IMT was 1.040 mm (SD 0.181 mm). A subset of 566 patients was eligible for a follow-up scan, which we performed in 487 (86%). The mean (SD) common carotid IMT at baseline was 0.571 mm (0.151), and after a 3 year follow-up, the common carotid IMT increased to a mean of 0.621 mm (0.171), an increase of 0.050 mm (0.055), P < 0.001. Among patients in the highest progression quartile, the common carotid IMT increased by 0.119 mm (0.062). The following serum cytokines were independently associated with the cross-sectional composite IMT, adjusted for age and sex: IL-8, 0.047 (0.018, 0.076); soluble IL-2 receptor-alpha, 0.054 (0.020, 0.089); IL1-receptor antagonist, -0.053, -0.087, -0.018); and macrophage-derived chemokine -0.027 (-0.052, -0.001). Values shown are regression coefficients in mm per SD (95%CI). Few cytokines were associated with rapid progression of the common carotid IMT, with only the IL-12p40 reaching statistical significance with an odds ratio of 1.67 per SD, 95% CI (1.14, 2.29).
A number of inflammatory cytokines measured in the serum, notably IL-8, were significantly associated with the carotid IMT. However, in contrast with other RA outcomes, the number of cytokines and the strength of their association with the carotid IMT were modest. This may indicate that cytokines and chemokines exert their effect at the level of the vascular wall rather than though the systemic circulation. These findings help clarify the role of inflammation in rheumatoid atherosclerosis.
I. del Rincon,
R. W. Haas,
D. H. O’Leary,
J. F. Polak,
D. F. Battafarano,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-cytokines-associated-with-carotid-atherosclerosis-in-rheumatoid-arthritis/