Arterial wall inflammation is increased in rheumatoid arthritis compared with osteoarthritis, as a marker of early atherosclerosis

Abstract

Objective RA is associated with higher risk of cardiovascular (CV) disease. Ongoing systemic inflammation is presumed to accelerate atherosclerosis by increasing inflammation in the arterial wall. However, evidence supporting this hypothesis is limited. We aimed to investigate arterial wall inflammation in RA vs OA, and its association with markers of inflammation and CV risk factors. Methods 18-fluorodeoxyglucose PET combined with CT (18F-FDG-PET/CT) was performed in RA (n = 61) and OA (n = 28) to investigate inflammatory activity in the wall of large arteries. Secondary analyses were performed in patients with early untreated RA (n = 30), and established RA, active under DMARD treatment (n = 31) vs OA. Results Patients with RA had significantly higher 18F-FDG uptake in the wall of the carotid arteries (beta 0.27, 95%CI 0.11—0.44, P <0.01) and the aorta (beta 0.47, 95%CI 0.17—0.76, P <0.01) when compared with OA, which persisted after adjustment for traditional CV risk factors. Patients with early RA had the highest 18F-FDG uptake, followed by patients with established RA and OA respectively. Higher ESR and DAS of 28 joints values were associated with higher 18F-FDG uptake in all arterial segments. Conclusion Patients with RA have increased 18F-FDG uptake in the arterial wall compared with patients with OA, as a possible marker of early atherosclerosis. Furthermore, a higher level of clinical disease activity and circulating inflammatory markers was associated with higher arterial 18F-FDG uptake, which may support a role of arterial wall inflammation in the pathogenesis of vascular complications in patients with RA.

Prospective, simultaneous assessment of joint and vascular inflammation by PET/CT in tofacitinib-treated patients with rheumatoid arthritis: associations with vascular and bone status

“… 31–35 In atherosclerosis, the evaluation of TBR was suitable to detect vessel wall inflammation 20 24 and the composition of plaques. 20 21 23 In RA, Agca et al 24 found increased arterial wall inflammation.…”

“…14 There have been reports on the examination of joints or blood vessel inflammation in RA by positron emission tomography (PET) or PET/CT. [17][18][19][20][21][22][23][24][25][26] There is increased 18 F-fluorodeoxyglucose (FDG) uptake in the arterial wall in RA, 24 26 27 as well as ankylosing spondylitis (AS) 28 and psoriatic arthritis. 29 18 F-FDG-PET was able to follow disease activity, joint destruction and…”

“… 14 There have been reports on the examination of joints or blood vessel inflammation in RA by positron emission tomography (PET) or PET/CT. 17–26 There is increased 18 F-fluorodeoxyglucose (FDG) uptake in the arterial wall in RA, 24 26 27 as well as ankylosing spondylitis (AS) 28 and psoriatic arthritis. 29 18 F-FDG-PET was able to follow disease activity, joint destruction and predict clinical outcome in patients with RA undergoing combination conventional synthetic disease-modifying antirheumatic drug (csDMARD), 30 anti-tumour necrosis factor, 17 31–33 rituximab 34 or tocilizumab therapy.…”

Imaging Study on Acupuncture Inhibiting Inflammation and Bone Destruction in Knee Osteoarthritis Induced by Monosodium Iodoacetate in Rat Model

“…36 18F-FDG PET/CT imaging is usually applied to detect the glucose uptake and metabolic changes in human diseases 37 using 18F-fluorodeoxyglucose (18F-FDG), a radioactively labelled glucose analogue, which is injected into the body to reflect the status of metabolism activities through the aggregation of radioactivity. 38,39 The 18F-FDG uptake was associated with serological and clinical markers of inflammation, 40 and the role of 18F-FDG PET in imaging inflammatory conditions has been validated in KOA. 41 The high expression of GLUT-1 receptor subtype in stimulated inflammatory cells such as macrophages is one of the potential mechanisms for 18F-FDG uptake in these inflammatory conditions.…”

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

“… 10 Clinical trials investigating arterial inflammation using FDG-PET imaging showed increased FDG aortic uptake in RA patients. 76 , 77 The central role of the inflammation is also supported by the mitigative effects of anti-inflammatory treatment regimens on the CVD risk. 7 , 46 , 49 , 78 , 79 The double-impact of inflammation on both RA progression and increased CVD risk led some authors to suggest that treatment with biologic DMARDs (such as TNF alpha inhibitors) amounts to “killing 2 birds with 1 biological stone.” 80 Currently ongoing TARGET trial ( https://targetra.org ) is aimed at understanding how different treatments for RA affect cardiac inflammation.…”