Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies

Abstract

Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.

Rheumatoid arthritis and coronary atherosclerosis: a two-sample Mendelian randomization study

“…However, some observational studies have drawn different conclusions. Fazeli Y et al found that the pathogenesis of the atherosclerosis process preceded the diagnosis of RA (24). Another study demonstrated that coronary artery calcification was no higher in RA patients compared to non-RA patients (64% vs. 52%, P = 0.31) (25).…”

Causal Relationship between Rheumatoid Arthritis and Atherosclerosis Risk: A Mendelian Randomized Study

“…Previous studies have shown that the onset of atherosclerosis precedes that of RA 27 , and there is an increasing belief that atherosclerosis is becoming a primary cause of rheumatoid arthritis 28 . In contrast, several cross-sectional studies have found that the incidence of coronary atherosclerosis, peripheral atherosclerosis, aortic valve sclerosis, and carotid atherosclerosis in RA patients is greater than that in the general population, sometimes even doubling [29][30][31][32] .…”

Silent Coronary Artery Disease in Patients with Rheumatoid Arthritis in Kurdistan, Iraq: A cross-sectional study

“…The anti-CCP autoantibodies and RF autoantibodies have a synergistic effect in mediating RA-associated inflammation and disease activity, and their presence was associated with a higher rate of CAC and CAD in patients with RA. [30][31][32] Choi and colleagues demonstrated in their study that methotrexate-treated patients had a 70% reduction in cardiac events compared with those not receiving the same therapy regularly. 33 Other disease-modifying drugs such as sulfasalazine, penicillamine, hydroxychloroquine, and gold did not confer this protection.…”