Investigation of atherosclerosis and the effects of anti- inflammatory therapy on plaque morphology in rheumatoid arthritis

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Abstract

IntroductionRheumatoid arthritis (RA) is a systemic autoimmune condition, characterised by an inflammatory arthritis. It is associated with a 50% increased risk of cardiovascular (CV) mortality. Chronic inflammation is thought to lead to accelerated atherosclerosis in RA. There is some evidence to suggest that patients have a more inflammatory, unstable atherosclerotic plaque phenotype. The impact of advances in RA treatment, on cardiovascular co-morbidity remains unclear. The aims of the current study were to employ non-invasive imaging techniques to test the hypothesis that RA patients have more inflammatory, unstable atherosclerotic plaques compared to unaffected individuals and that treatment of active arthritis would lead to alterations in plaque composition and inflammation. Secondary aims were to evaluate the association of clinical phenotype and potential serological biomarkers of CV risk with plaque presence and phenotype.MethodsA prospective pilot study of patients with active RA and age and sex matched controls was conducted. Subjects underwent clinical and serological evaluation, then carotid artery ultrasound was performed to screen for carotid plaque. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) was performed on those with suitable plaque. A subgroup of patients had a carotid artery positron emission tomography (PET) scan. Patients were followed up with repeat clinical, serological and DCE-MRI assessments. The primary outcome evaluated was difference in plaque inflammation measured on DCE-MRI between patients and controls and in patients longitudinally. Secondary outcomes included differences in plaque composition on DCE-MRI, plaque inflammation on PET and the relationship of clinical, serological and imaging findings.Results130 patients and 52 controls were recruited and screened for carotid plaque. There was a higher prevalence of plaque on ultrasound in the patient group (53% vs 36%) and plaque was independently associated with high sensitivity c reactive protein (hsCRP). Carotid DCE- MRI data was analysed in 15 patients and 5 controls. There was no significant difference in plaque inflammation on DCE-MRI between the groups. However there was a significantly higher rate of plaque calcification in patients, despite similar plaque burden in both groups (73.3% vs 20%, p=0.038). All 15 patients exhibited features of high-risk plaque. Plaque inflammation was seen in all 13 patients in whom PET imaging was undertaken. No significant improvement in plaque inflammation was detected on DCE-MRI over time, which was in keeping with the lack of clinical improvement found in most cases. ConclusionsIncreased prevalence of atherosclerosis and differences in plaque phenotype were observed in this study and findings would support the hypothesis that patients have a more high-risk plaque phenotype. The high prevalence of calcified lesions in RA is a novel finding which warrants further investigation. The study was underpowered to detect significant changes in plaque inflammation, measured on DCE-MRI, between the groups and in patients over time. However, this study provides valuable data with which to plan a larger study to investigate the effects of anti-inflammatory therapy on atherosclerosis in RA in the future.

Layman's Abstract

Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). It is thought that inflammation accelerates the growth of arterial "plaques" which can rupture causing clinical events such as heart attack. It may also be that inflammation alters the composition of plaques, making them more likely to rupture. Imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) can be used to visualise inflammation in plaques in the arteries of the neck and also identify features of the plaque which could suggest they are more likely to rupture. In the current study the aim was to employ these imaging techniques to investigate whether patients with RA had more inflamed rupture prone plaques compared to people without RA. Patients with RA and healthy volunteers were invited to have blood tests and an ultrasound scan which was used to identify if participants had evidence of plaques in the neck artery. If plaque was found on ultrasound, participants went on to have an MRI scan of the neck to evaluate the composition and inflammation of the plaque. Some patients with plaque also had a PET scan. 130 patients and 52 healthy volunteers took part in the study. 15 patients and 5 volunteers had an MRI scan. 13 patients also had a PET scan. While no difference in plaque inflammation was measured on MRI, patients were more likely to have calcium within the plaques, a marker of high risk plaques. On PET scanning all 13 patients had inflammation in the plaques in the neck arteries.This study suggests that patients with RA may have more rupture prone arterial plaques compared to people of the same age, who do not have RA. However a larger study is required to investigate this further.

Keyword(s)

atherosclerosis; rheumatoid arthritis

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