Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness

Abstract

IntroductionIn this study we aimed to investigate whether there are indications of premature atherosclerosis, as measured by endothelial dependent flow-mediated dilation (ED-FMD) and intima media thickness (IMT), in patients with very early RA, and to analyze its relation to biomarkers of endothelial dysfunction, taking inflammation and traditional cardiovascular disease (CVD) risk factors into account.MethodsPatients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study of CVD co-morbidity. Of these, all patients aged ≤60 years were consecutively included in this survey of CVD risk factors (n = 79). Forty-four age and sex matched controls were included. IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography. Blood was drawn for analysis of lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA)-mass, VonWillebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), sE-selectin, sL-selectin and monocyte chemotactic protein-1 (MCP-1). In a subgroup of 27 RA patients and their controls the ultrasound measurements were reanalysed after 18 months.ResultsThere were no significant differences between RA patients and controls in terms of IMT or ED-FMD at the first evaluation. However after 18 months there was a significant increase in the IMT among the patients with RA (P < 0.05). Patients with RA had higher levels of VWF, sICAM-1 (P < 0.05) and of MCP-1 (P = 0.001) compared with controls. In RA, IMT was related to some of the traditional CVD risk factors, tPA-mass, VWF (P < 0.01) and MCP-1 and inversely to sL-selectin (P < 0.05). In RA, ED-FMD related to sL-selectin (P < 0.01). DAS28 at baseline was related to PAI-1, tPA-mass and inversely to sVCAM-1 (P < 0.05) and sL-selectin (P = 0.001).ConclusionsWe found no signs of atherosclerosis in patients with newly diagnosed RA compared with controls. However, in patients with early RA, IMT and ED-FMD were, to a greater extent than in controls, related to biomarkers known to be associated with endothelial dysfunction and atherosclerosis. After 18 months, IMT had increased significantly in RA patients but not in controls.

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease

“…Atherogenesis is a chronic inflammatory process of the arterial wall, finally leading to endothelial dysfunction [10,11], which involves the alteration of the control of the vascular tone, leukocytes trafficking and platelets adhesion. The risk of early onset of atherosclerosis is well known in individuals suffering from other chronic inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus [12][13][14], thus it should not be surprising that, in the last decade, an increasing body of data, both epidemiological and clinical, have supported this association also in IBD.…”

Changes in vascular function and structure in juvenile idiopathic arthritis

“…In adult populations with CID, indices of subclinical atherosclerosis have been well documented (10 -12) and related to worse cardiovascular prognosis (1,12). In patients with CID, vascular dysfunction appears to occur at a relatively young age (13,14). However, there are limited data on indices of premature atherosclerosis (15,16) in patients with JIA.…”

Atherosclerosis in Patients with Rheumatoid Arthritis

“…Further, inflammatory disorders, characterized by high levels of CRP, can develop a secondary immune cell activation, which may result in atherogenesis [54]. In addition, studies have demonstrated that inflammatory related markers such as lipoproteins, ox-LDLs [55], NO [55], TNF-a [56], RANKL [57], CD40L [58], IL-18 [59], MMP-9 [60], MCP-1 [61], insulin [45], EPCs [51] in atherosclerosis are altered in patients with RA. These evidences thus support the theory that systemic inflammation plays a crucial role in the pathogenesis of CVD in patients with RA.…”