Imaging atherosclerotic plaque inflammation in rheumatoid arthritis: methodology and initial findings in a single centre cohort study

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1 Imaging atherosclerotic plaque inflammation in rheumatoid arthritis: methodology and initial findings in a single centre cohort study Dr. Sarah Skeoch Clinical Research Fellow Centre for Musculoskeletal Research University of Manchester

2 Disclosures No conflicts of interest

3 Introduction Rheumatoid arthritis(ra) is associated with a 50% increase in cardiovascular mortality Less warning symptoms and worse outcomes Risk varies within the RA population No reliable method to identify high risk patients early in disease

4 Atherosclerosis Known to be a chronic inflammatory condition Plaque inflammation and composition are key determinants of plaque stability J Am Coll Cardiol. 2011;57(20):

5 Atherosclerosis Known to be a chronic inflammatory condition Plaque inflammation and composition are key determinants of plaque stability J Am Coll Cardiol. 2011;57(20):

6 Atherosclerosis in RA Driven by chronic inflammation Paucity of histological evidence about the type of lesions in RA There may be a more inflammatory, unstable plaque phenotype Impact of anti-inflammatory therapies is unclear Low grade inflammation may continue to drive atherosclerosis

7 Contrast enhanced carotid MRI Allows assessment of: Burden Phenotype Inflammation Validated against histology Carotid MRI and matched histology. Chu.B. Radiology 2009 Used to study predictors of cardiovascular events and effects of lipid lowering therapy on plaque

8 18F FDG-PET-CT Detects plaque inflammation Correlates with histology and clinical symptoms Sensitive to change following treatment FDG-MRI of symptomatic carotid artery plaque. Rudd. J.H Aortic PET used to detect vascular inflammation in RA

9 Hypothesis Carotid MRI and PET imaging could be employed to detect atherosclerotic plaque inflammation in patients with RA

10 Aims To test the feasibility of using carotid MRI and PET to evaluate plaque inflammation in RA patients To assess if there was an early indication that RA patients have inflamed plaque Inform a larger study to investigate plaque phenotype in RA

11 Methods

12 Study population Prospective pilot study Inclusion criteria Age years Diagnosis of RA >1 year Active joint disease (DAS-28 score> 3.2) Major exclusion criteria Statin therapy within the last 3 months Renal Impairment (egfr<60) Contra-indication to MRI

13 Study design Plaque >2mm thickness present No history of recent infection, uncontrolled diabetes or cancer

14 Results

15 Recruitment and retention 57 Patients screened 12 (21%) had plaque>2mm thickness 6 (10%) had plaque confirmed on MRI

16 Cohort characteristics Characteristics of MRI cohort Median [IQR] or frequency (total=6) Female 5 Median age (years) 57[55,59] Current smoker 3 History of CVD 1 RA disease duration (years) 9[2,20] LDL cholesterol (mmol/l) 2.82[2.13, 3.03] ESR(mm/hr) 29[17,35] Disease activity 28 score 5.15[4.69, 6.55] Degree of vessel stenosis (%) 54.5[48,59]

17 MRI showing plaque inflammation

18 MRI showing plaque inflammation Lumen Plaque

19 MRI showing plaque inflammation Lumen Plaque

20 MRI showing plaque inflammation Lumen Plaque

21 MRI showing plaque inflammation Lumen Lumen Plaque Plaque K trans Contrast enhancement was seen in all cases (median K trans =0.046[0.023, 0.105] min -1 ) All lesions were calcified and 5/6 had evidence of lipid core

22 18F FDG-PET Significant 18F FDG uptake was seen in all cases (Median SUV max =2.22[1.67, 2.95])

23 Summary Initial findings suggest plaque inflammation can be detected using both techniques Prevalence of suitable plaque was lower than estimated There is an discrepancy between ultrasound and MRI findings

24 Further work Larger prospective case control study of RA patients with longitudinal follow up Future applications: Study natural history of atherosclerosis in RA Evaluation of new and existing therapies

25 Acknowledgements Supervisors Professor Ian Bruce Professor John Waterton Professor Yvonne Alexander Funding and support * Collaborators Penny Hubbard Heather Williams Paul Hockings Jacqueline James Mary Prescott Department of Radiology, University of Washington Participating Centres in the North West NIHR Manchester Musculoskeletal Biomedical Research Unit NIHR/ Wellcome Trust Clinical Research Facility Greater Manchester Clinical Research Network *North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the Medical Research Council (grant number G /94909), ICON, GlaxoSmithKline, AstraZeneca and the Medical Evaluation Unit.

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