Short summary

Cardiovascular disease and pulmonic disease are the most common causes of the elevated morbidity and mortality in Rheumatoid Arthritis (RA) patients. Low vitamin D levels are associated to elevated cardiovascular risk in otherwise healthy subjects. The aim of this study is, in 150 newly diagnosed RA patients, we will extensively evaluate cardiovascular and pulmonic comorbidity, and associate the 2- and 5 year progression in comorbidity to baseline vitamin D metabolite levels.

---

Rationale

RA is a systemic, chronic autoimmune disease, characterized by synovial inflammation, the production of auto-antibodies (IgM-RF and ACPA), destruction of cartilage and bone, as well as systemic affection, including cardiovascular, pulmonary and skeletal disorders. The systemic inflammation is probably the major contributor to the reduced expected lifespan in RA patients, compared to the background population, mainly due to cardiovascular and pulmonic comorbidities.

Pro-inflammatory processes, similarly to those in RA, are active in cardiovascular disease, and atherosclerosis; an early predictor of cardiovascular disease, is now known to be an inflammatory process, predominated by a cytokine-profile similar of the profile in RA.

Interstitial lung disease, (ILD) another common comorbidity in RA is also associated to the inflammatory process, and the prevalence of ILD is especially elevated in sero-positive RA patients.                    

Several studies indicate a connection between low vitamin D metabolite levels and RA, with vitamin D levels affecting the development as well as the disease-course of RA.

In otherwise healthy controls, low levels of vitamin D are associated to increased risk of cardiovascular disease, but till now, the effect of low levels of vitamin D on the progression of cardiopulmonal comorbidity in early diagnosed RA patients, has not been investigated.

In patients with ILD, especially those with connective disease associated ILD, low vitamin D levels seem to be associated to reduced lung-function, compared to the lung-function in those with normal vitamin D levels.

The aim of this study is, in 150 early diagnosed, treatment-naïve RA patients, at the Diagnostic Center (DC), Regional Hospital Silkeborg, to evaluate baseline vitamin D levels (25OHD₂, 25OHD₃ and D_total), and to associate this to progression in cardiovascular and pulmonic comorbidity. The project will evaluate if vitamin D shall be part of a baseline algorithm for predicting later serious development of co-morbidity in RA patients 2 and 5 years after prognosis.

The cohort will be extensively evaluated at baseline and after 2 and 5 years with use of CT and MRI of the heart, speckle tracking echocardiography, extended lung function, central vessel wall stiffness (pulse wave velocity), insulin resistance, whole body DXA scanning for body composition, clinically co-morbidity scoring (Charlson index) and scoring of heart/lung function (NYHA and MRC score).

Standardized disease activity parameters (clinical and imaging database) and relevant plasma and serum will be stored for later use.

Any co-morbidity diagnosed during the disease course, will be further evaluated and treated by consultants in the relevant disciplines, according to national guidelines

The cardiovascular endpoints are worsening of the heart function; decreasing myocardial perfusion, evaluated by MRI, and progression of coronary atherosclerosis, evaluated by CT of the heart after 2 years of follow-up.

Pulmonary co-morbidity will be evaluated by extended lung function test and 5-minute walking test.

Finally, baseline D vitamin metabolite levels will be associated to the development of cardiovascular events evaluated using systematic journal audit after 2 years.

This study is a sub-study of a PhD-project. You can read about another sub-study here:  OP_339 Prognostic value of vitamin D metabolite levels for 10 year cardiovascular events and mortality in rheumatoid arthritis patients from the CIMESTRA study.

---

Description of the cohort

Our cohort is planned to include 150 treatment-naïve RA, diagnosed  using the ACR/EULAR 2010 RA criteria, at the Diagnostic Center (DC), Regional Hospital Silkeborg. There are no exclusion criteria, except age below 18. The absence of clinical exclusion criteria makes it suitable for the purpose of evaluating the presence and development of comorbidities that are often considered exclusion criteria in RCT studies.  

Data and biological material

Blood-samples are collected at baseline, year 2 and 5 after diagnosis, with established Biobank for future use.

Physician´s evaluation about RA disease activity parameters (Number of swollen and tender joints, Health Assessment Quality Score (HAQ), VAS-scores and DAS28 (Disease Activity Score; a composite disease activity score calculated in 28 joints)), as well as evaluation of number of tender points and antopomethric measures is obtained at each visit.

Imagine techniques; Speckle Track Echocardiography, CT and MR of the hearth and full-body DEXA scans are obtained

Functional analyses; extended lung functioning test and walking distance are registered.

Collaborating researchers and departments

Department of Rheumatology, Odense University Hospital

• PhD fellow Mette Herly, MD 
• Professor Torkell Ellingsen, MD, PhD

Department of Cardiology, Aarhus University Hospital, Skejby

• Brian Bridal Løgstrup, MD, PhD 

Department of Rheumatology, Diagnostic Centre, Silkeborg Regional Hospital

• Trine Bay Laurberg, MD, PhD
• Jesper Blegvad, MD

Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital

• Professor Robin Christensen, BSc, MSc, PhD

Medical Department, Diagnostic Centre, Silkeborg Regional Hospital

• Grazina Urbonaviciene, MD, PhD

Radiological Department, Diagnostic Centre, Silkeborg Regional Hospital

• Christin Isaksen, MD
• Agnete Hedemann Nielsen, MD

Department of Clinical Medicine and Endocrinology, Aalborg University Hospital

• Professor Peter Vestergaard, MD, PhD