The Epidemiological and Pathogenic Association of Rheumatoid Arthritis With Atherosclerotic Cardiovascular Disease

Introduction

Rheumatoid arthritis (RA), an inflammatory rheumatic disease, is associated with increased risk of atherosclerotic cardiovascular disease (CVD) including myocardial infarction (MI) and stroke. The association of RA with CVD was first described over four decades ago. Increasingly, the role of inflammatory and immune mechanisms in the pathogenesis of atherosclerosis and CVD, even among the general population, is becoming apparent. Hence, the association of RA with CVD has two broad implications. First, as a disease model of accelerated atherosclerosis, RA has the potential to reveal important insights into the pathogenic mechanisms, risk factors, and biomarkers of CVD in general. Second, with advances in the treatment of musculoskeletal manifestations of RA through the availability of targeted immunotherapies, complications such as CVD assume renewed importance as major potential causes of morbidity and mortality among patients with RA.

Abstract

Rheumatoid arthritis (RA) is associated with an approximately twofold increased risk of atherosclerotic cardiovascular disease (CVD) including myocardial infarction and stroke. The increased risk of CVD in RA is due to an interplay between traditional risk factors such as hyperlipidemia, hypertension, and smoking and disease-related variables such as the presence of rheumatoid factor and anticyclic citrullinated peptide antibodies, high erythrocyte sedimentation rate, and joint swelling. Systemic inflammation and immune mechanisms form a pathogenic link between synovitis and atherosclerosis in RA. Indeed, high levels of C-reactive protein, an inflammatory marker, predict cardiovascular mortality in RA. Furthermore, the risk of CVD is greatly diminished among patients who respond to disease modifying antirheumatic drugs and biological therapies such as tumor necrosis factor (TNF) alpha antagonists. Through adverse effects on lipid profile and blood glucose level, long-term use of high-dose glucocorticoids in RA also increases cardiovascular risk. However, through control of active disease, glucocorticoids may also indirectly attenuate cardiovascular risk. Through their lipid-lowering and immunomodulatory effects, statins may have a dual benefit in the treatment of patients with RA. However, data on cardiovascular risk reduction in RA through management of traditional risk factors remain scant. Current research efforts are directed toward elucidating the risk factors for CVD in RA and developing strategies to minimize this risk.

Keywords

rheumatoid arthritis, atherosclerosis, cardiovascular disease