Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis

Abstract

Aim To determine in a prospective study factors of progressive atherosclerotic lesion of blood vessels in patients with rheumatoid arthritis (RA).Material and methods This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD) and 30 patients with IHD (comparison group) aged 58 [52; 63] years. On enrollment to the study and at 3 years of follow-up, all patients underwent clinical and instrumental examination according to European and Russian guidelines for diagnosis and treatment of stable IHD (2013), including coronography as indicated. For all RA patients of the comparison group, risk factors (RF) were evaluated, including arterial hypertension, smoking, excessive body weight, family history of cardiovascular diseases (CVD), diabetes mellitus, and dyslipidemia. The following laboratory data were evaluated: blood count; biochemistry, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), rheumatoid factor (RhF), cyclic citrullinated peptide antibodies, and high-sensitivity C-reactive protein (hsCRP). Proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF- α), were measured in RA patients once, at 3 years of follow-up.Results Incidence of FRs for CVD was similar in RA patients and in the comparison group. Median RA duration before inclusion into the study was 11 years, and median DAS28 index score was 3.8. Incidence of dyslipidemia due to increased TC, LDL-C, and HDL-C was higher for RA patients at baseline. The LDL-C goal (<1.8 mmol/l) was achieved only in 3 (10 %) patients of the comparison group and 10 (8 %) RA patients. RA patients had higher levels of the inflammation indexes, hsCRP (0.75 mg/dl vs. 0.16 mg/dl; p<0.05) and erythrocyte sedimentation rate (ESR) (15 mm/h vs. 11.5 mm/h; p<0.05). In the RA group at baseline, atherosclerotic plaques with carotid artery (CTA) stenosis of 20% or more were found in 94 (77 %) patients; in 3 of them, CA stenosis was >50%. Patients with RA frequently had unchanged or slightly changed coronary arteries (CA) (47% of patients), and less frequently they had hemodynamically significant multi-arterial coronary atherosclerotic lesions (7 % vs. 57 % of patients in comparison group). At 37.5 months, 21 (23 %) of 94 RA patients had progressive atherosclerosis in CA and/or CTA; 12 (13 %) RA patients had only progressive CA atherosclerosis; 7 (8 %) had only progressive CTA atherosclerosis; and 2 (2 %) had simultaneous progression of CA and CTA atherosclerosis. Two groups of RA patients were formed, with the progression of atherosclerosis (n=21) and without the progression of atherosclerosis (n=69). RFs for the development/progression of atherosclerosis in RA patients included smoking, family history of CVD, and duration of the disease. Levels of lipids did not differ. Levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α) were higher in RA patients with progressive atherosclerosis. No effects of the anti-rheumatic therapy on the progression of atherosclerosis were observed.Conclusion Progression of atherosclerosis in RA remains in disease with low and moderate activity during the anti-rheumatic and hypolipidemic treatment. The development of atherosclerosis in RA is determined by lipid, inflammatory, and immune disorders.

Subclinical Carotid Atherosclerosis in Patients with Rheumatoid Arthritis at Low Cardiovascular Risk

“…It has been shown that chronic systemic inflammation plays an important role in accelerated atherogenesis in autoimmune diseases. Inflammation can have a direct impact on the development of atherosclerosis or indirectly enhance the effect of traditional cardiovascular risk factors [ 14 , 31 , 32 ]. One of the mechanisms of the atherosclerotic process connecting inflammation and atherothrombosis is the activation of the CD40/CD40L signaling system.…”

“…It is known that the progression of the immunopathological process in RA is accompanied by the development of a wide range of immunoinflammatory reactions, which may have pathophysiological significance in the development of atherosclerosis. The imbalance of cytokines and the accumulation of inflammatory mediators contribute to the development of vascular disorders associated with atherogenesis—endothelial dysfunction, vasoconstriction, lipid and lipoprotein peroxidation, hypercoagulation—and later lead to the formation and destabilization of atherosclerotic plaques and the development of cardiovascular complications [ 13 , 14 ]. It was shown that in the assessment of early atherosclerotic vascular changes, the prognostic significance of soluble CD40 ligand (sCD40L) and adhesion molecules—intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1)—was significantly higher compared to other biological mediators [ 15 , 16 ].…”

Rheumatoid arthritis and cardiovascular diseases: close relatives or friends?

“…Фомичева и соавт. [44] в течение 3 лет наблюдали 124 больных РА с подозрением на ишемическую болезнь сердца (ИБС). На момент включения в исследование атеросклеротические бляшки в сонных артериях были выявлены в 77% случаев, атеросклеротическое поражение коронарных артерий -в 7%.…”