Background/Purpose: Interleukin (IL) 1, and its family member, IL-1 receptor antagonist (IL-1ra), are involved in the pathogenesis and inflammation perpetuation of patients with rheumatoid arthritis (RA). Besides, IL-1ra has been linked to an increased risk and greater severity of cardiovascular (CV) diseases. We aimed to study in a large series of patients with RA whether this interleukin is related to the CV disease –including lipid pattern and insulin resistance or subclinical atherosclerosis– that accompanies the disease.

Methods: Cross-sectional study that encompassed 430 patients with RA. Serum IL-1ra levels were assessed. A multivariable analysis was performed to analyze the relation of IL-1ra to subclinical carotid atherosclerosis, and to traditional CV factors including a complete lipid molecules profile and insulin resistance or beta cell function indices.

Results: Body mass index (beta coef.- 22 [95%CI 14-30] pg/ml, < 0.001), abdominal circumference (beta coef. 8 [95%CI 5-11) pg/ml, p< 0.001) and the presence of obesity (beta coef. 169 [95%CI 78-260] pg/ml, p< 0.001) were positively associated with circulating IL-1ra. Neither carotid intima-media thickness nor the presence of carotid plaque were associated with serum levels of IL-1ra. ESR, and DAS28-ESR, DAS 28-CRP and CDAI indices were significant related to IL-1ra after adjustment for confounders. This was not the case for other disease characteristics like the presence of rheumatoid factor or anti-citrullinated protein antibodies, or the use of several treatments. Only patients under hydroxychloroquine disclosed a negative relation to IL-1ra although significance was not achieved (beta coef. -125 [95%CI -253-3] pg/ml, p=0.055). After multivariable analysis, IL1-ra was associated with higher serum levels of total cholesterol, triglycerides, non-HDL cholesterol, and apolipoproteins B and C-III. Remarkably, this was found after adjustment for age, diabetes, BMI and waist circumference. IL-1ra was associated with higher levels of beta cell dysfunction (HOMA2-B%) in the univariable analysis (beta coef. 24 [95%CI 138-4], p=0.019). However, after full multivariable analysis this relation was lost (this analysis was only performed in patients with RA that were non-diabetes and had a glycemia inferior to 110 mg/dl).

Conclusion: IL-1ra is associated with both the clinical activity of the disease and the CV risk factors like dyslipidemia and insulin resistance indices that are present in RA. Our findings suggest that IL-1ra could represent a link between the inflammation and CV disease of RA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interleukin-1-receptor-antagonist-relation-to-cardiovascular-disease-in-patients-with-rheumatoid-arthritis/