HuLIAS – Hunt Longitudinal Inflammatory Arthritis Study

HuLIAS is a longitudinal study of inflammatory arthritis (joint disease) in HUNT – the population-based Trøndelag Health Study. We focus on rheumatoid arthritis, ankylosing spondylitis and other forms of axial spondyloarthritis (arthritis that mainly affect joints of the pelvis and vertebral column), as well as psoriasis arthritis.

The aims of HuLIAS are to investigate

• associations among different types of risk factors for cardiovascular disease in persons with inflammatory arthritis, including lifestyle factors, inflammation, and genetic predisposition
• changes in the prevalence and complications of inflammatory joint diseases over time
• which lifestyle changes persons with inflammatory joint diseases may do to improve their quality of life and reduce their risk of complications, with specific focus on physical activity
• genetic variants that are associated with increased risk of developing inflammatory arthritis

Several of our studies are performed in collaboration with researchers in other countries. Deeper understanding of the mechanisms that lead to development of arthritis and complications is important to improve diagnostics, treatment, and prevention.

HuLIAS is a follow-up study after the previous HuLARS study – Hunt Longitudinal Ankylosing spondylitis and Rheumatoid arthritis Study. We now study participants from HUNT2 (1995-1997), HUNT3 (2006-2008), and HUNT4 (2017-2019). We have identified participants with rheumatoid arthritis, ankylosing spondylitis and other forms of axial spondyloarthritis, and psoriasis arthritis. Some persons have participated in several HUNT surveys, permitting studies of long-term changes in risk factors and complications. Linkage to the Norwegian Cardiovascular Disease Registry and the Norwegian Cause of Death Registry have given access to further outcome data. The protocols are approved by the Regional Committee for Medical and Health Research Ethics (REK). Important funding has been given from NTNU and St. Olavs University Hospital, the Central Norway Regional Health Authority, and the Research Council of Norway.  

Some important findings regarding inflammatory joint disease so far:

• Cardiovascular fitness is lower in persons with rheumatoid arthritis, and also declines more rapidly by age, than in other participants in HUNT
• Persons with rheumatoid arthritis have higher death rates than persons without. In other words: they are younger when they die. Lower cardiovascular fitness is an important cause. Inflammation also has an influence, but low cardiovascular fitness was about three times more important. These findings are significant because fitness may be improved by appropriate physical training
• When accounting for age, the increased death rates in persons with rheumatoid arthritis are lower up to the age of 75 than in persons with diabetes. In the older age groups, there is no difference in death rates between persons with rheumatoid arthritis and with diabetes
• Persons who have had angina, myocardial infarction, or stroke have an increased risk of developing rheumatoid arthritis
• Smoking doubles the risk of developing ankylosing spondylitis. Previous research has shown that smoking also is a strong risk factor for rheumatoid arthritis. If you have relatives with these diseases, you may have an increased genetic predisposition to develop them. Then avoidance of smoking is an important contribution to reducing your risk
• Data from HUNT have contributed to finding novel risk gene variants for ankylosing spondylitis
• Risk scores composed of multiple genetic risk variants combined with non-genetic risk factors may identify groups persons with increased risk of developing either rheumatoid arthritis or ankylosing spondylitis, but the scores are not sufficiently accurate to be used in individuals
• More complicated genetic risk scores for rheumatoid arthritis do not necessarily give better prediction of future disease development than simpler scores
• The genetic risk factors for myocardial infarction are not different in patients with rheumatoid arthritic compared to other HUNT participants
• Self-report is not sufficient to ensure that someone has rheumatoid arthritis or ankylosing spondylitis. Information from a rheumatologist is necessary

Fyskond1 and Fyskond2 – Factors that influence physical activity and cardiovascular fitness in persons with inflammatory joint disease

In the Fyskond studies, we also investigate persons with inflammatory arthritis and the diagnoses rheumatoid arthritis, ankylosing spondylitis and other forms of axial spondyloarthritis, or psoriasis arthritis. We have also collected data from student and healthy blood donors (controls) to compare the findings.

The aims of the Fyskond studies are

• to develop methods to evaluate cardiovascular fitness in persons with inflammatory joint disease without performing a treadmill og bicycle ergometer test
• to perform studies using questionnaires and tests that characterize both physical, psychological, and practical aspects that may influence physical activity and cardiovascular fitness
• to investigate the usefulness of different physical functional tests and questionnaires for motivation and facilitators/barriers to physical activity in the Fyskond populations

The data are used to answer a number of research questions, for example:

• How active are the different groups?
• Does motivation for physical activity differ between persons with different forms of inflammatory joint disease and the controls?
• Which physical, psychological, and practical factors are most important when it comes to restricting the patient's levels of physical activity?
• Which associations exist among the different physical, psychological, and practical factors that were measured?

Some important findings regarding physical activity and fitness in persons with inflammatory joint disease so far:

• Cardiovasular fitness in persons with rheumatoid arthritis may be estimated using a simple formula when the person’s age, sex, body mass index, smoking habits, physical activity habits, and subjective evaluation of disease level is known

Risk calculator 

CERG

Similar formulae developed for the general population give too high results in persons with RA and lowest fitness, which is unfavorable

• Cardiovascular fitness in persons with rheumatoid arthritis is associated with their subjective evaluation of disease level, but not with objective measurements from blood samples, joint examinations, etc.
• Persons with rheumatoid arthritis perceive more barriers to physical activity than controls. A new questionnaire (FasBarPAQ) is useful to assess factors acting as facilitators or barriers to physical activity and may probably be useful in other patient groups
• In persons with rheumatoid arthritis, perceived self-efficacy and the subjective evaluation of disease level influence how far one walks in a 6-minute walk test. The test provides an estimate of the person’s overall physical function
• In persons with rheumatoid arthritis, physical symptoms and negative emotions are important factors explaining why they have reduced cardiovascular fitness compared to controls
• BREQ-2 (Behavioral Regulation in Exercise Questionnaire-2) is useful to evaluate motivation for physical activity in persons with rheumatoid arthritis. Motivation played an important role for how active the study participants were and their cardiovascular fitness. This finding is important because health care providers can stimulate increased motivation for physical activity

We are working on collecting data from the groups with other inflammatory joint diseases.

Background information on inflammatory joint disease

Rheumatoid arthritis is found in 0.5-1% of the population and is more common in women. Smoking increases the risk of rheumatoid arthritis twofold or more. The disease affects large and small joints and may also affect many internal organs, including the cardiovascular system. If left untreated, rheumatoid arthritis results in serious joint damage and substantial functional deficits. Intensive modern treatment has given enormous improvements, but many persons with rheumatoid arthritis still suffer from pain and fatigue.

Persons who develop psoriasis arthritis have often had the skin disease psoriasis for several years before they get symptoms from the joints. About 20% of persons with psoriasis develop joint disease, amounting to 0.1-0.6% of the population. Persons with psoriasis arthritis often have inflammation where tendons are inserted into bone and in complete fingers or toes. They may also get inflammation in the vertebral column. The disease affects men and women to a similar extent. Without treatment, it can lead to destruction of the joints. Despite modern treatment, many persons with psoriasis arthritis still suffer from reduced quality of life and risk of complications, including cardiovascular disease.

Ankylosing spondylitis and other forms of axial spondyloarthritis affect 0.2-0.8% of the population, with a higher frequency in young men. The disease especially affects the joints between the vertebral column and the pelvis (the sacroiliac joints) and the joints in the vertebral column. Formation of bony connections over the joints lead to increasing stiffness and pain, which has a large influence on the quality of life. Many also develop eye inflammation (uveitis) with substantial pain. MRI scans have made it possible to identify persons with inflammation in the mentioned joints (axial spondyloarthritis) long before the person develops joint changes that can be seen on X-rays. Modern treatment seems to be able to reduce or stop development of serious joint changes in many patients.