Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis

Abstract

Objectives Patients 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. Methods Patients 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. Results At 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. Conclusions This 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.

Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis: Associations with Vascular Pathophysiology

“…In this study, MPO variably and positively correlated with CRP, IMT and PWV supporting its role in RA-related inflammation and atherosclerosis [35,36]. MPO correlated with diseases activity in other RA studies [56]. In the general population, MPO levels and PON activity were inversely correlated [34], but it was not found under inflammatory conditions in our arthritis patients.…”

Detection of Citrullinated Fibrin in Plasma Clots of Rheumatoid Arthritis Patients and Its Relation to Altered Structural Clot Properties, Disease-Related Inflammation and Prothrombotic Tendency

“…This circumstance holds true for RA, with elevated levels of both pro-inflammatory and prothrombotic markers (e.g. D-dimer Fibrinogen Tissue Factor (TF) and von Willebrand factor (vWF)), which is associated with one another and with the risk of future cardiovascular complications (6).…”

The Atypical Fibrin Fibre Network in Rheumatoid Arthritis and its Relation to Autoimmunity, Inflammation and Thrombosis

“…C-reactive protein (CRP) (7)(8)(9)(10)(11), Tumor necrosis factor alpha (TNFα) (7,9,11), Interleukin-6 (IL-6) (7-12), IL-1β (7) and Serum Amyloid A (SAA) (10,13,14)] and prothrombotic markers [e.g. D-dimer (8,9,11,15,16), Fibrinogen (10,11,16,17), Tissue Factor (TF) (15), and von Willebrand factor (vWF) (8,16,18)], which is associated with one another (7,19) and with the risk of future cardiovascular complications (20)(21)(22)(23).…”