Abstract
ObjectivesPatients with rheumatoid arthritis (RA) have an increased mortality and morbidity due to cardiovascular disease (CVD). In this prospective 5-year follow up of patients with RA, we analysed several biomarkers, known to be associated with atherosclerosis and/or inflammation in the general population. The aim of this study was to find out whether the RA-disease per se affect these biomarkers and if those could be associated with the progression of atherosclerosis, as measured by intima media thickness (IMT) among patients with early RA.MethodsPatients from northern Sweden diagnosed with early RA, are consecutively recruited into an ongoing prospective study on CVD comorbidity. A subgroup of patients, aged ≤60 years (n = 71) was included for ultrasound measurements of IMT at inclusion (T0) and after 5 years (T5) together with age-sex-matched controls (n = 40). The patients were clinically assessed. Blood was analysed for lipids, ESR and CRP and several biomarkers known to be associated with atherosclerosis in the general population.ResultsAt T0, the patients with RA had significantly lower levels of MIF and significantly higher levels of interleukin (IL)-18 and MIC-1 compared with controls. At T5, the patients with RA had significantly higher levels of pentraxin3, MIC-1, TNF-R2, ICAM-1, VCAM-1 and endostatin compared with controls. At T0 the levels of MPO correlated with DAS28, sCD40L with CRP and IL-18 with systolic blood pressure and Reynolds risk score. Using PLSR on a CVD-panel analysed with multiplex immunoassay, the patients with RA could be correctly classified into those who had a worsening in their IMT over the five years or not. Here, MMP3 was identified as influential.ConclusionsThis study indicates that the RA disease itself could affect several of the biomarkers in this study, and possibly also the processes involved in the development of atherosclerosis.
Highlights
Patients with rheumatoid arthritis (RA) have an increased atherosclerosis compared with the general population [1,2,3,4,5]
At T5, the patients with RA had significantly higher levels of pentraxin3, macrophage inhibitory cytokine 1 (MIC-1), TNF-R2, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1) and endostatin compared with controls
Using partial least squares regression (PLSR) on a cardiovascular disease (CVD)-panel analysed with multiplex immunoassay, the patients with RA could be correctly classified into those who had a worsening in their intima media thickness (IMT) over the five years or not
Summary
Patients with rheumatoid arthritis (RA) have an increased atherosclerosis compared with the general population [1,2,3,4,5]. Others, have previously shown that patients with established RA have a premature atherosclerosis as measured by an increased IMT of the common carotid artery (CCA) compared with controls [11,12,13]. This ultrasound measured indicator is not available and, further, has disadvantages like lack of possibility to detect the very early phases of the development of atherosclerosis. The identification of such new biomarkers may improve the prediction of cardiovascular events and death
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