Variables associated with subclinical atherosclerosis in a cohort of rheumatoid arthritis patients: Sex-specific associations and differential effects of disease activity and age.

Delia Taverner,Joan-Carles Vallvé,Lluís Masana,Antoni Castro,Lluís Masana,Silvia Paredes,Joan-Carles Vallvé,Joan-Carles Vallvé,Raimón Ferré,Antoni Castro,Raimón Ferré,Antoni Castro,Lluís Masana,Raimón Ferré

doi:10.1371/journal.pone.0193690

Abstract

ObjectiveTo advance the study of variables associated with subclinical atherosclerosis in rheumatoid arthritis (RA) with special consideration for the degree of disease activity, age and gender.MethodsThe carotid intima-media thickness (cIMT) and the presence of carotid atherosclerotic plaques along with clinical and biochemical characteristics were determined in 214 RA patients.ResultsAdjusted analysis reveals that men had a 0.059 mm significantly increased cIMT compared with women (p = 0.001; R2 = 3.8%) and that age was associated with cIMT (β = 0.0048 mm; p = 0.0001; R2 = 16%). Interestingly, we observed a significant interaction between gender and age. Thus, the effect of age on cIMT was significantly increased (12%) in men compared with women (p-value for interaction term = 0.041). Moreover, adjusted multivariable linear regression analysis revealed that disease activity score (DAS28) was significantly associated with cIMT in women (β = 0.021; p = 0.018: R2 = 0.03) but not men. In particular, women with high disease activity had a 0.079 mm increased cIMT compared with women in remission (p = 0.026). In addition, men in remission had a 0.134 mm increased cIMT compared with women in remission (p = 0.003; R2 = 8.7%). Active patients did not exhibit differences in cIMT values. Furthermore, 43% of patients presented carotid plaques. The variables independently associated with carotid plaques were age, smoking, health assessment questionnaire, erythrocyte sedimentation rate and rheumatoid factor (p<0.0001; R2 = 46%).ConclusionIn our cohort of patients with RA, DAS28 and age are differentially associated with cIMT in men and women. Our findings could explain the contradictory results that have previously been published in the literature.

Highlights

Rheumatoid arthritis (RA) is a systemic autoimmune disease that mainly affects synovial joints and causes chronic pain, bone erosion and progressive disability
Adjusted analysis reveals that men had a 0.059 mm significantly increased carotid intima-media thickness (cIMT) compared with women (p = 0.001; R2 = 3.8%) and that age was associated with cIMT (β = 0.0048 mm; p = 0.0001; R2 = 16%)
The effect of age on cIMT was significantly increased (12%) in men compared with women (p-value for interaction term = 0.041)

Summary

Introduction

Rheumatoid arthritis (RA) is a systemic autoimmune disease that mainly affects synovial joints and causes chronic pain, bone erosion and progressive disability. With a prevalence of up to 0.5–1% of the general population, RA is the most common chronic inflammatory disease [1,2]. In addition to joint involvement, a high prevalence of comorbidities and an increase in cardiovascular (CV) risk characterizes RA patients compared with the general population [1,3]. RA can be considered an independent risk factor for developing CV disease (CVD), with its prevalence being as high as in patients with type 2 diabetes mellitus [4] and leading to an increase in the standardized mortality rate of up to 3.82 for acute myocardial infarction in the United States [5]. The chronic inflammatory state of RA seems to contribute to the development of accelerated atherosclerosis because the inflammatory process in the synovial membrane and atherosclerotic plaques share similar characteristics [6]

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Conclusion