OP0042 WHICH FACTORS ARE IMPORTANT FOR THE PROGRESSION OF ATHEROSCLEROSIS IN RHEUMATOID ARTHRITIS?
S. WÅllberg Jonsson, M. öhma , S. Rantapää-Dahlqvist

Previous studies have shown that mortality and morbidity due to cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA). The purpose of this study was to identify what factors might be associated with this increase.

Methods: Thirty-nine patients with seropositive RA, originally followed up in a retrospective cohort study on predictors of cardiovascular disease, were assessed with ultrasound of the common carotid artery (CCA) and the common femoral artery (CFA) of the right side, for intima-media thickness (IMT) and presence and size of atherosclerotic plaque. Potential predictors for IMT of the CCA and presence and grade of atherosclerotic plaques of the CCA and the CFA were assessed in the 39 RA patients and in 39 age-and sex-matched controls.

Results:

• Using simple binary logistic regression, atherosclerotic plaques were predicted by age at disease onset, IMT-CCA, smoking, PAI-1 mass, cholesterol (chol), LDL-chol, ICAM-1, E-Selectin and IL-2sRa in RA.
• Using multiple binary logistic regression, presence of plaques was associated with age, chol and E-Selectin. Serious plaques were predicted by disease duration and LDL-chol.
• Using simple linear regression, IMT-CCA was significantly predicted by age, tPAag, chol, LDL-chol and triglycerides. Presence of and grade of plaques were also associated with IMT-CCA.
• Using multiple linear regression modeling, variables associated with increasing IMT-CCA were sICAM-1 and chol. Methotrexate (MTX) decreased the IMT-CCA, although not quite reaching statistical significance.
• Using multiple logistic regression in a 1-1 matched case-control study manner, the best model of variables associated with RA included PAI-1 mass, sICAM-1 and ESR. In another model, CCA-IMT was, together with d-Dimer, associated with RA per se.

Summary: These data indicate that cholesterol and adhesion molecules are associated with IMT and with atherosclerotic plaques in patients with RA. Disease duration may be predictive of serious atherosclerotic plaques. MTX seems to decrease the IMT associated with RA.

Editorial Comment: This is a cross-sectional analysis in a small number of patients of risk factors in RA associated with the presence of atherosclerotic plaque or IMT in the carotid artheries. It is not clear whether these patients had clinically diagnosed CV disease or were asymptomatic. In multivariate analyses for either or both outcomes, age, adhesion molecules and cholesterol were significantly associated with these measures of atherosclerosis, while MTX appeared to be protective.

These studies of subclinical atherosclerosis, although limited in scope, support studies of clinical CV events in RA, suggesting that RA is an independent predictor of atherosclerosis. The association of adhesion molecules with plaque and IMT supports the role of inflammation and vascular dysfunction in this process, as does the negative correlation of MTX with plaque and IMT. Accelerated atherosclerosis occurs early in SLE but probably late in RA as suggested by the association of disease duration with severe plaque. Interestingly, steroid use was neither protective nor a risk factor for atherosclerosis. This may represent a net effect of zero, in which high dose steroids have an adverse effect via promotion of an adverse lipid profile while low dose steroids have a protective effect via their anti-inflammatory action (without lipid effect).

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