Can rheumatoid arthritis and cardiovascular co-morbidity be predicted in anti-CCP and/or IgM RF positive persons with arthralgia using PET/CT and clinical/metabolic variables (PETRACOR)?
With this cohort study, we aim to identify and diagnose rheumatoid arthritis and cardiovascular co-morbidity at an earlier stage in a group of persons that we know is in a high risk of developing disease. We will examine these persons with a broad range of clinical/metabolic parameters and as the first research group evaluate signs of early disease activity using PET/CT. We hope the knowledge from this study will guide the clinician to identify patients earlier and thereby give them an opportunity to start treatment and preventive initiatives so poor outcome of the disease can be prevented.
Rheumatoid arthritis (RA) is a chronic, autoimmune disease affecting up to 1% of the Danish population. The disease is characterized by inflammation, which untreated leads to destruction of the joints and functional disabilities.
RA is diagnosed using a set of criteria including swollen joints, duration of symptoms, acute phase reactants and autoantibodies, including anti-CCP and/or IgM RF. The autoantibodies can often be detected years before disease onset and the fact that these autoantibodies often present together with arthralgia (tender, but not swollen joints) could indicate early disease activity, which is just not jet diagnosable from the existing diagnostic criteria.
However, we know that the majority of persons with arthralgia and positive autoantibody status will develop the disease within 5 years. But until then they remain untreated despite that effective treatment strategies have been developed, reducing the permanent joint destructions in patients with even early RA.
People with RA are also more likely to be affected by other diseases indicating that RA should be considered as a systemic inflammatory disease. Consequently, there has been increased attention regarding co-morbidity among patients with RA, especially concerning cardiovascular disease. The increased cardiovascular co-morbidity is not explained by smoking, BMI, diabetes or hypertension showing that the diagnosis of RA is an independent risk factor.
Patients with RA show an increased risk of cardiovascular disease equal to patients with type 2 diabetes. In addition to the higher risk of developing cardiovascular disease, patients with RA, also have a more severe disease course with higher risk of dying in relation to a heart attack compared to other patient groups. Moreover cardiovascular disease is the primary course of death for almost half of the patients with RA.
The association between RA and cardiovascular co-morbidity also appears to be related to the presence of the autoantibodies anti-CCP/ IgM RF and interestingly, it appears that the increased degree of cardiovascular co-morbidity is present already in the years before the diagnosis of RA.
Because patients with arthralgia and positive anti-CCP and/or IgM RF status show a high risk of developing RA within a few years and that the risk of cardiovascular disease is present already before the diagnose of RA, it would be useful to develop new methods to identify disease at an earlier stage.
The aim of our study is therefore to evaluate whether clinical/metabolic and/or PET/CT scans can detect any early disease activity and if this will predict who that develops RA and/or cardiovascular disease.
We hope that the knowledge from our study will guide the clinician to identify patients at an earlier stage and thereby an opportunity to start treatment and preventive initiatives earlier, so long term effects and pure outcome of the disease can be minimized and prevented.
Description of the cohort
The study is a prospective, open, inception cohort including early referral patients with peripheral arthralgia being anti-CCP and/or IgM RF positive. The participants will be included from two outpatient clinics in Denmark - including Rheumaclinic, Funen, Odense and the Department of Rheumatology, Odense University Hospital.
Inclusion criteria: All patients with arthralgia and positive anti-CCP and /or IgM RF will be offered participation. Exclusion criteria: Age < 18 years, previous cancer, breastfeeding women and pregnancy. The study will include a total of 160 persons.
Data and biological material
Data is collected several times: Baseline, 1 year visit, 2 years call, 5 years call, RA-diagnosis visit Personal data \n
- Sex (female %) - Baseline \n
- Age (years) - Baseline \n
- Height (cm) - Baseline \n
- Body weight (kg) - Baseline, 1 year visit, RA-diagnosis visit \n
- Waist-hip-ratio - Baseline, 1 year visit, RA-diagnosis visit \n
- Smoker status (yes/no) - Baseline, 1 year visit, RA-diagnosis visit \n
- Patient Evaluation \n
- Symptom duration (days) - Baseline \n
- Patient tender/swollen (joint score) - Baseline, 1 year visit, RA-diagnosis visit \n
- Patient global/pain/fatigue (VAS 0-100 mm) - Baseline, 1 year visit, 2 years call, 5 years call, RA-diagnosis visit \n
- HAQ (0-3) - Baseline, 1 year visit, 2 years call, 5 years call, RA-diagnosis visit \n
- Doctor evaluation \n
- Doctor tender/swollen joints (40/38) - Baseline, 1 year visit, RA-diagnosis visit \n
- Doctor's global (VAS 0/100 mm) - Baseline, 1 year visit, RA-diagnosis visit \n
- DAS 28 - Baseline, 1 year visit, RA-diagnosis visit \n
- Ultrasound (joint score) - Baseline, 1 year visit, RA-diagnosis visit \n
Blood samples (Baseline, 1 year visit, RA-diagnosis visit) \n
- C-reactive protein (mg/L) \n
- IgM RF (UI/mL) \n
- Anti-CCP (UI/mL) \n
Cardiovascular disease (5 year call) \n
- Corevent score md Gæde - 5 years call \n
PET/CT (Baseline, RA-diagnosis visit) \n
- FDG-PET/CT \n
- NaF-PET/CT \n
Collaborating researchers and departments
Department of Nuclear Medicine, Odense University Hospital
- Poul Flemming Høilund-Carlsen
- Søren Hess
- Björn Blomberg
Reumaclinic Funen, Odense
Division of Nuclear Medicine, Department of Radiology, Hospital of the University of Pennsylvania, USA
Department of Medical Center Freiburg, Freiburg, Germany
Clinical Biochemistry and Pharmacology, Odense University Hospital
Institute for Molecular Medicine, University of Southern Denmark
- Uffe Holmskov
- Grith Lykke Sørensen
Department of Cardiology, Aarhus University Hospital