title: Evaluation of carotid plaque inflammation in patients with active rheumatoid arthritis using (18)F-fluorodeoxyglucose PET-CT and MRI: a pilot study.
abstract: BACKGROUND
  Rheumatoid arthritis is associated with a 50% increased risk in cardiovascular mortality. Inflammation is thought to accelerate atherosclerosis and might also lead to an inflammatory rupture-prone plaque phenotype. We tested the hypothesis that patients with active rheumatoid arthritis also have carotid plaque inflammation and that plaque inflammation correlates with clinical and serological markers of inflammation.
  
  
  METHODS
  Patients with active rheumatoid arthritis, defined as the Disease Activity Score in 28 joints (DAS28) score of more than 3·2, were recruited to a single centre study in the UK. Patients with carotid plaque on ultrasound underwent carotid MRI followed by (18)F-fluorodeoxyglucose ((18)F-FDG) PET-CT. Scans were co-registered and analysed by a physicist, masked to clinical information. The maximum standardised uptake values (SUV(max)) were measured in the plaque area. The association of SUV with DAS28, C-reactive protein, and CD4+CD28- T-cell frequency was tested with non-parametric statistics. Ethics approval and informed consent were obtained.
  
  
  RESULTS
  Scans were done in 13 patients, nine of whom were women. Median age was 60 years (IQR 57-65), disease duration was 11 years (6-25), and DAS28 score was 4·52 (4·32-5·13). None had a history or symptoms of clinical cardiovascular disease or took statins. All plaques caused less than 70% stenosis, and tracer uptake in plaque was seen on PET in all 13 patients. Median SUV(max) was 2·18 (IQR 2·00-2·65), and all cases had an SUV(max) greater than 1·6 (the threshold for defining carotid plaque inflammation). There was a significant association with SUV(max) and C-reactive protein (r=0·58, p=0·04) and quartiles of CD4+CD28- T-cell frequency (p=0·045), but not with low-density lipoprotein concentrations (r=-0·49, p=0·09) or DAS28 score (r=0·38, p=0·20). No association was found with age (r=0·13, p=0·69) or sex (p=0·64).
  
  
  CONCLUSIONS
  In this small pilot study, plaque inflammation was seen in all patients and correlated with C-reactive protein. Whether this finding represents simultaneous joint and plaque inflammation, which might improve on treatment of joint disease, remains to be determined. CD4+CD28- T-cells are known to predict cardiovascular events in patients with angina. Their association with plaque inflammation in this study suggests a possible role in cardiovascular risk prediction in rheumatoid arthritis. Larger studies are warranted to investigate these findings further.
  
  
  BACKGROUND
  North West England MRC Clinical Pharmacology and Therapeutics Clinical Research Fellowship, National Institute for Health Research, AstraZeneca-University of Manchester Strategic Alliance Fund.
authors: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; NIHR Manchester Musculoskeletal Biomedical Research Unit, University of Manchester, Manchester, UK. Electronic address: sarah.skeoch@postgrad.manchester.ac.uk.
authors: Sarah
authors: S
authors: Skeoch
authors: Biomedical Imaging Institute, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors: Heather
authors: H
authors: Williams
authors: Biomedical Imaging Institute, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors: Penny
authors: P
authors: Cristinacce
authors: Drug Safety and Metabolism, AstraZeneca, Molindal, Sweden; MedTech West, Chalmers University of Technology, Gothenburg, Sweden.
authors: Paul
authors: P
authors: Hockings
authors: Department of Nuclear Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors: Jacqueline
authors: J
authors: James
authors: Healthcare Science Research Institute, Manchester Metropolitan University, Manchester, UK.
authors: Yvonne
authors: Y
authors: Alexander
authors: AstraZeneca Personalised Healthcare & Biomarkers, Alderley Park, Macclesfield, UK.
authors: John
authors: J
authors: Waterton
authors: The Kellgren Centre for Rheumatology, NIHR Manchester, Manchester, UK.
authors: Ian
authors: I
authors: Bruce