Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout

Abstract

The increased risk of cardiovascular morbidity and mortality in rheumatoid arthritis and gout has been increasingly acknowledged in past decades, with accumulating evidence that gout, just as with rheumatoid arthritis, is an independent cardiovascular risk factor. Although both diseases have a completely different pathogenesis, the underlying pathophysiological mechanisms in systemic inflammation overlap to some extent. Following the recognition that systemic inflammation has an important causative role in cardiovascular disease, anti-inflammatory therapy in both conditions and urate-lowering therapies in gout are expected to lower the cardiovascular burden of patients. Unfortunately, much of the existing data showing that urate-lowering therapy has consistent beneficial effects on cardiovascular outcomes in patients with gout are of low quality and contradictory. We will discuss the latest evidence in this respect. Cardiovascular disease risk management for patients with rheumatoid arthritis and gout is essential. Clinical guidelines and implementation of cardiovascular risk management in daily clinical practice, as well as unmet needs and areas for further investigation, will be discussed.

Figure 1

Rheumatoid arthritis, gout, and their shared pathophysiological mechanisms behind cardiovascular comorbidities The histological image (left) shows synovitis in rheumatoid arthritis. The polarisation microscopy image (right) illustrates monosodium urate crystals in synovial fluid during a gout flare.

Figure 2

Summary of shared mechanisms in the development of cardiovascular disease in patients with rheumatoid arthritis and gout The left column describes gout and rheumatoid arthritis-related mechanisms inducing atherosclerosis. NET=neutrophil extracellular trap.

Figure 3

Shared mechanisms in the development of heart failure with preserved or reduced ejection fraction in patients with rheumatoid arthritis and gout Systemic inflammation with elevated concentrations of circulating cytokines, such as IL-6 and TNF, induce oxidative stress and endothelial activation. Consequently, presentation of adhesion molecules (VCAM-1 and E-selectin) by endothelial cells leads to monocyte infiltration in the myocardium. These monocytes produce TGF-β, resulting in the differentiation of fibroblasts into myofibroblasts, with subsequent deposition of collagen in the interstitial space. In addition, intracellular oxidative stress results in disrupted crosstalk between endothelial cells and cardiomyocytes, leading to stiffness and hypertrophy of cardiomyocytes with a subsequent decreased ability to contract and relax. These processes ultimately lead to preclinical diastolic ventricular dysfunction, which might evolve into heart failure with preserved ejection fraction. Ischaemia, mostly secondary to atherosclerosis, leads to autophagy, apoptosis, and necrosis of cardiomyocytes, and deposition of collagen in the interstitial space. This condition can give rise to systolic ventricular dysfunction, which in severe cases can lead to heart failure with reduced ejection fraction. Adapted from Paulus and Tschöpe, by permission of Elsevier. ROS=reactive oxygen species.