Effect of high-intensity interval training in physiotherapy primary care for patients with inflammatory arthritis: the ExeHeart randomised controlled trial.

OBJECTIVES: To assess the effect of high-intensity interval training (HIIT) delivered in physiotherapy primary care on the primary outcome of cardiorespiratory fitness (CRF) in patients with inflammatory arthritis (IA). Additionally, to explore the effects of HIIT on secondary outcomes, including cardiovascular disease (CVD) risk factors and disease activity. METHODS: Single-blinded randomised controlled trial with 60 patients randomly assigned to either a control group receiving usual care or an exercise group receiving usual care and 12 weeks of individualised HIIT at 90%-95% peak heart rate. Outcomes were assessed at baseline, 3 months and 6 months post baseline and included CRF measured as peak oxygen uptake (VO2peak), classic CVD risk factors, disease activity, anthropometry and patient-reported physical activity, pain, fatigue, disease impact and exercise beliefs and self-efficacy. RESULTS: Intention-to-treat analysis demonstrated a significant between-group difference in VO2peak at 3 months (2.5 mL/kg/min, 95% CI 0.9 to 4.0) and 6 months (2.6 mL/kg/min, 95% CI 0.8 to 4.3) in favour of the exercise group. A beneficial change in self-reported physical activity in favour of the exercise group was observed at 3 and 6 months. The HIIT intervention was well-tolerated with minimal adverse events and no apparent impact on disease activity. Differences in secondary outcomes related to CVD risk factors, disease impact, pain, fatigue and exercise beliefs and self-efficacy were generally small and non-significant. CONCLUSION: After 12 weeks of supervised HIIT delivered in physiotherapy primary care, patients with IA demonstrated a favourable improvement in CRF, with sustained effects at 6-month follow-up. TRIAL REGISTRATION NUMBER: NCT04922840.

Associations between cardiovascular risk factors, disease activity and cardiorespiratory fitness in patients with inflammatory joint disease: a cross-sectional analysis.

BACKGROUND: Inflammatory joint diseases (IJD) are accompanied by an increased risk of cardiovascular disease (CVD). Cardiorespiratory fitness (CRF) is a modifiable CVD risk factor and low levels of CRF associate with an elevated CVD risk. This study aimed to investigate the associations between CVD risk factors, disease activity and CRF in patients with IJD and to explore differences between patients with normal versus low levels of CRF. METHODS: CRF was measured as peak oxygen uptake (VO2peak) with a cardiopulmonary exercise test. Participants were also evaluated for: Body composition, blood pressure, blood lipids, inflammatory markers and disease activity. Patient-reported use of cigarettes/snuff, medication, disease duration, pain, fatigue, CVD history, habitual physical activity and exercise beliefs and self-efficacy were collected by questionnaire. Cross-sectional associations between CVD risk factors, disease-related factors and CRF were analyzed by multiple linear regression. CRF was categorized to normal CRF (VO2peak ≥ 80%) or low CRF (VO2peak < 80%) according to age- and gender-stratified reference data. Differences in demographic, CVD and disease-related factors between patients with normal versus low CRF were explored. RESULTS: In 60 Norwegian patients with IJD [34 females, age 59 years (IQR: 52-63)], mean VO2peak was 30.2 (± 6.9) mL/kg/min, corresponding to 83% (± 18) of normative reference values. Age (coefficient: - 0.18 years, p = 0.01) and fat mass (coefficient: - 0.67 %, p < 0.001) were inversely associated with CRF, while physical activity index (coefficient: 0.13 points, p = 0.05) was positively associated with CRF (R2 = 0.66). There were no significant associations between CRF, classical CVD risk factors and disease-related variables. Compared to patients with low CRF (n = 30), patients with normal CRF (n = 30) had higher peak oxygen uptake (+ 9.4 mL/kg/min, p < 0.001), high-density lipoprotein cholesterol (+ 0.5 mmol L-1, p < 0.001), and exercise self-efficacy (+ 6.9, p < 0.01) as well as lower fat mass (- 8.7%, p < 0.001), resting heart rate (- 8.0 beats/min, p < 0.01) and triglycerides (- 0.5 mmol L-1, p < 0.01). CONCLUSIONS: In this sample of IJD-patients, age, fatmass and physical activity level were associated with CRF. CRF was lower than reference values and patients with normal CRF presented with a more favorable health profile. There is a continued need for exercise interventions to improve CRF in patients with IJD. TRIAL REGISTRATION: NCT04922840.

Relationship between types of radiographic damage and disability in patients with rheumatoid arthritis in the EURIDISS cohort: a longitudinal study.

OBJECTIVE: The aim of this study was to assess if any of the different types of radiographic damage [true joint space narrowing (JSN), (sub)luxation and erosions] are preferentially related to disability in patients with RA. METHODS: Longitudinal data from 167 RA patients from the European Research on Incapacitating Diseases and Social Support study over 10 years were analysed to investigate the relationship between the three types of radiographic damage and disability [grip strength, HAQ and the dexterity scale in the Arthritis Impact Measurement Scales (AIMS)]. A longitudinal analysis including separate models per type of damage and joint group and combined models including all information was conducted. RESULTS: All types of damage were inversely related to grip strength in the analysis of separate models, but only true JSN independently remained statistically significant in the combined analysis [ß = -0.087 (95% CI -0.151, -0.022)]. Neither JSN, (sub)luxation nor erosions were associated with HAQ score, while erosions were associated with AIMS dexterity only in the analysis of separate models. After stratifying for hand joint group, erosions at MCP joints [ß = -0.288 (95% CI -0.556, -0.019)] and true JSN at the wrist [ß = -0.132 (95% CI -0.234, -0.030)] were significantly related to grip strength. Erosions at the PIP [ß = 0.017 (95% CI 0.005, 0.028)] and MCP joints [ß = 0.114 (95% CI 0.010, 0.217)] was the only type of damage associated with HAQ and AIMS dexterity, respectively. CONCLUSION: All types of radiographically visible joint damage interfere with important aspects of physical functions. True JSN is most closely related to hand function.

Exploring Tai Chi in rheumatoid arthritis: a quantitative and qualitative study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory and systemic disease which affects the musculoskeletal system. Exercise programmes are reported to improve physical functioning in patients with RA. Tai Chi is a traditional Chinese martial art which combines slow and gentle movements with mental focus. The purpose of this study was to study in which way Tai Chi group exercise impacted on disease activity, physical function, health status and experience in RA patients, applying quantitative and qualitative methods. METHODS: Fifteen patients with RA (13 females, age 33-70 years) were recruited from a rheumatology department into a single group study. The patients were instructed in Tai Chi exercise twice weekly for 12 weeks. Assessments at baseline, 12 weeks, and 12 weeks follow-up were performed with a wide range of measures, including disease activity, self-reported health status, physical performance tests (Walking in Figure of Eight, Timed-Stands Test, and Shoulder Movement Impairment Scale). Qualitative data were obtained from a focus group interview conducted after completed intervention with taping and verbatim transcription. Review of the transcripts identified themes important to patients practicing Tai Chi. RESULTS: Within the group, Tai Chi practice lead to improved lower-limb muscle function at the end of intervention and at 12 weeks follow-up. Qualitative analyses showed that patients experienced improved physical condition, confidence in moving, balance and less pain during exercise and in daily life. Other experience included stress reduction, increased body awareness, confidence in moving and indicated that Tai Chi was a feasible exercise modality in RA. CONCLUSIONS: Improved muscle function in lower limbs was also reflected when patient experiences with Tai Chi were studied in depth in this explorative study. The combination of qualitative and quantitative research methods shows that Tai Chi has beneficial effects on health not related to disease activity and standardised health status assessment, and may contribute to an understanding of how Tai Chi exerts its effects. TRIAL REGISTRATION: NCT00522054.

Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study.

INTRODUCTION: Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration. METHODS: 163 patients with RA of short disease duration (2.4 years) were included and followed longitudinally. Antibodies to cyclic citrullinated protein (anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed from baseline blood-samples. Hand BMD was measured by digital X-ray radiogrammetry (DXR) based on hand and wrist radiographs obtained at baseline and 1, 2 and 5-year follow-up. RESULTS: During the study period, DXR-BMD decreased by median (inter quartile range) 1.7% (4.1 to 0.4), 2.8% (5.3 to 0.9) and 5.6% (11.7 to 2.3) after 1, 2 and 5 years, respectively. Elevated baseline anti-CCP, RF, ESR and CRP levels were in univariate linear regression analyses consistently associated with DXR-BMD change at all time-points. Anti-CCP and ESR were independently associated with hand DXR-BMD in multivariate linear regression analyses. Elevated anti-CCP levels were consistent and independent predictors of loss in cortical hand bone during the study period, with the odds ratios (95% confidence interval) 2.2 (1.0 to 4.5), 2.6 (1.1 to 6.2) and 4.9 (1.4 to 16.7) for the 1, 2, and 5-year follow-up periods, respectively. CONCLUSIONS: Anti-CCP and ESR were found to be independent predictors of early localised BMD loss. This finding adds to the understanding of anti-CCP and ESR as important predictors of bone involvement in RA.

Cartilage and bone biomarkers in rheumatoid arthritis: prediction of 10-year radiographic progression.

OBJECTIVE: As current predictors of joint destruction have low specificity, serological biomarkers reflecting bone and cartilage destruction have been proposed as tools in assessing prognosis of rheumatoid arthritis (RA). We examined whether serum concentrations of a panel of biomarkers could predict radiographic progression in patients with RA. METHODS: A cohort of 238 patients with RA was followed longitudinally for 10 years with collection of clinical data and serum samples. These analyses focus on the 136 patients with radiographs of the hands available at baseline and at 5 and/or 10 years. Radiographs were scored according to the van der Heijde-modified Sharp score (SHS). Baseline sera were analyzed for receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), human cartilage glycoprotein-39 (YKL-40), C2C, collagen cross-linked C-telopeptide (CTX-I), and cartilage oligomeric matrix protein (COMP). Multivariate linear and logistic regression analyses were used to identify predictors of radiographic progression. RESULTS: Baseline CTX-I levels were higher in progressors [0.41 ng/ml (interquartile range 0.31-0.75)] than in nonprogressors [0.32 ng/ml (IQR 0.21-0.49)], and were independently associated with 10-year change in radiographic damage score [ss = 16.4 (IQR 5.7-27.1)]. We found no association between radiographic progression and baseline serum levels of RANKL, OPG, C2C, YKL-40, or COMP. CONCLUSION: This longterm followup study of patients with RA indicates a relationship between elevated CTX-I levels in serum and subsequent joint destruction. This association was, however, weak, and our study does not support that serum CTX-I or any of the other tested biomarkers will serve as more useful prognostic markers than current predictors such as anti-cyclic citrullinated peptide, radiographic damage early in the disease course, and signs of inflammation.

The association between disease activity and NT-proBNP in 238 patients with rheumatoid arthritis: a 10-year longitudinal study.

INTRODUCTION: Disease activity in patients with rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, of which N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. Our objective was to examine the cross-sectional and longitudinal associations between markers of inflammation, measures of RA disease activity, medication used in the treatment of RA, and NT-proBNP levels (dependent variable). METHODS: Two hundred thirty-eight patients with RA of less than 4 years in duration were followed longitudinally with three comprehensive assessments of clinical and radiographic data over a 10-year period. Serum samples were frozen and later batch-analyzed for NT-proBNP levels and other biomarkers. Bivariate, multivariate, and repeated analyses were performed. RESULTS: C-reactive protein (CRP) levels at baseline were cross-sectionally associated with NT-proBNP levels after adjustment for age and gender (r2 adjusted = 0.23; P < 0.05). At the 10-year follow-up, risk factors for cardiovascular disease were recorded. Duration of RA and CRP levels were independently associated with NT-proBNP in the final model that was adjusted for gender, age, and creatinine levels (r2 adjusted = 0.38; P < 0.001). In the longitudinal analyses, which adjusted for age, gender, and time of follow-up, we found that repeated measures of CRP predicted NT-proBNP levels (P < 0.001). CONCLUSION: CRP levels are linearly associated with levels of NT-proBNP in cross-sectional and longitudinal analyses of patients with RA. The independent associations of NT-proBNP levels and markers of disease activity with clinical cardiovascular endpoints need to be further investigated.

Incidence of clinically important 10-year health status and disease activity levels in population-based cohorts with rheumatoid arthritis.

OBJECTIVE: To calculate the average age- and sex-specific annual incidence of rheumatoid arthritis (RA) linked to clinically important levels of health status after 10 years, and to study time trends in 10-year disease status during a 6-year period. METHODS: Patients between 20 and 79 years of age with onset of RA from 1988 to 1993 (n = 550) were asked to participate in a 10-year followup examination. Two hundred sixteen patients in different age and sex groups from 6 different annual cohorts met during the period 1998-2003. Study variables included demographic variables, medication, swollen, tender and deformed joint counts, erythrocyte sedimentation rate, Disease Activity Score (DAS28), Health Assessment Questionnaire, and pain and fatigue on a 100 mm visual analog scale and Arthritis Impact Measurement Scale 2. Age- and sex-specific incidences of RA exceeding clinically important levels 10 years after disease onset were calculated using the Poisson distribution with 95% confidence intervals. Analysis of covariance and logistic regression were used to test the influence of time on 10-year DAS28 and presence of deformed joints. RESULTS: The average annual incidence of cases exceeding clinically important levels in disease activity and health status 10 years after disease onset increased with higher age and was highest among women. There was a tendency to lower disease activity 10 years after disease onset in the latest cohorts compared to the earliest cohorts. CONCLUSION: These results from population-based RA incidence cohorts provide important information to healthcare planners and support findings of secular decline in disease burden.

Associations between the PTPN22 1858C->T polymorphism and radiographic joint destruction in patients with rheumatoid arthritis: results from a 10-year longitudinal study.

OBJECTIVE: To investigate whether the PTPN22 1858T risk variant is associated with the rate of radiographic progression in rheumatoid arthritis (RA). METHODS: A longitudinally followed cohort of 238 Norwegian patients with RA (the EURIDISS cohort) was genotyped for the PTPN22 1858C-->T polymorphism. Radiographic damage was assessed by hand radiographs at baseline and after 1, 2, 5 and 10 years, and the radiographs were scored with the Sharp method modified by van der Heijde (Sharp-van der Heijde score) by a single experienced reader. Baseline serum levels of rheumatoid factor and anti-cyclic citrullinated peptide autoantibodies were also examined. RESULTS: The reported association between RA susceptibility and carriage of the T allele (34.4% in patients vs 21.4% in controls; odds ratio 1.92, 95% confidence interval 1.36 to 2.71, p = 0.0002) was confirmed. An association between annual progression rate of Sharp-van der Heijde score and T-allele carriers (p = 0.01),was also found, which was also present when only patients positive for the shared epitope were analysed (p = 0.03). This association was also maintained in multivariate analyses adjusting for shared epitope and demographic variables. CONCLUSIONS: An association between the PTPN22 risk variant and increased progression rate for structural damage was found. The results indicate that the PTPN22 gene may not only be associated with disease susceptibility, but also with disease progression.

Pain and psychological health status over a 10-year period in patients with recent onset rheumatoid arthritis.

OBJECTIVE: To examine rheumatoid arthritis (RA) with short disease duration over 10 years, and to identify factors that are associated with the course of pain, depression and anxiety. METHODS: A cohort of 238 patients with RA (age 20-70 years, mean disease duration 2.3 years, 68% rheumatoid factor positive) was followed with assessments at baseline and after 1, 2, 5 and 10 years. Self-reported health status was assessed by pain on a 100 mm visual analogue scale, the Arthritis Impact Measurement Scales (AIMS), the 28-item version of General Health Questionnaires, and the Health Assessment Questionnaire. We also examined the erythrocyte sedimentation ratio, grip strength (kg) and radiographic progression of the hands (van der Heijde modified Sharp score). Repeated measures analyses of variance were used to explore the effect of time on measures of outcome among completers, whereas repeated measures analyses using a mixed model were applied to identify factors that were longitudinally associated with pain, depression and anxiety. RESULTS: At the various assessment points 30% had a visual analogue scale pain score of > or =40 mm, 5-13% had an AIMS depression score of > or =4.0 and 20-30% had an AIMS anxiety score of > or =4.0. The perceived level of pain was explained longitudinally by anxiety, disease activity, physical function and female gender, depression by high disease activity and anxiety, whereas anxiety was explained by low disease activity and depression. CONCLUSION: More patients had increased levels of anxiety (20-30%) than increased levels of depression (5-13%). Several factors, including anxiety, but not depression, were associated with the course of pain.

Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis.

OBJECTIVE: Calprotectin is a major leucocyte protein, shown to correlate well with laboratory and clinical assessments in several inflammatory rheumatic diseases, and large concentrations of calprotectin have been found in synovial fluid from patients with rheumatoid arthritis (RA). The objective of the present study was to examine correlations between calprotectin and joint damage. METHODS: 145 patients with RA were analysed cross sectionally with laboratory (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28 and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs; modified Sharp's method) measurements, on the same day. RESULTS: Calprotectin showed a highly significant correlation with measures of joint damage; modified Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR, rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p = 0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any independent associations. Highly significant correlations (p<0.001) were also found between calprotectin and both laboratory and clinical markers of inflammation. CONCLUSION: Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.

Epidemiological aspects of rheumatoid arthritis: the sex ratio.

Many rheumatic diseases, including rheumatoid arthritis (RA) are more frequent in females than males. The objective of this article was to examine the female versus male perspective regarding prevalence/incidence, etiological factors, disease severity/outcomes, access to therapy and therapeutic responses. We also present results from some new analyses from the patient registers in Oslo to supplement existing literature in this area. We found that the prevalence of RA is higher in females than males, the incidence is 4-5 times higher below the age of 50, but above 60-70 years the female/male ratio is only about 2. Smoking is a consistent predictor of RA in males, but findings have been more inconsistent in females. We could not confirm that health status is worse in females than males when corrections were made for different disease duration and for the underlying tendency of healthy females to report worse subjective health status than males. Some studies and data presented here indicate that females have less access to health services. We also found that female sex reduces the likelihood of achieving treatment response with methotrexate and anti-tumor necrosis factor (anti-TNF) drugs by 30-50%. More research is needed to fully describe the differences between males and females regarding epidemiological data.

Positive affect as a factor of resilience in the pain-negative affect relationship in patients with rheumatoid arthritis.

OBJECTIVE: The purpose of this study is to examine positive affect (PA) as a factor of resilience in the relationships between pain and negative affect (NA) in a sample of patients with rheumatoid arthritis. METHODS: Forty-three patients (30 women; mean age, 57 years) were interviewed weekly by telephone for 8 weeks. Multilevel modeling was applied to study the within-week relationships among the variables. RESULTS: There was a Pain x PA interaction effect on NA (beta=-0.05, P<.01) indicating a weaker relationship between pain and NA in weeks with more PA. Pain (beta=0.37, P<.002), interpersonal stress (beta=2.42, P<.001), depression (beta=0.26, P<.01), average perceived stress (beta=10.80, P<.001), and also weekly PA (beta=-0.1, P<.01) had a main effect upon NA. CONCLUSION: Positive affect is most influential in reducing NA during weeks of higher pain and may be a factor of resilience, helping patients experiencing pain fluctuations as less distressful than at lower levels of PA.

Association of early radiographic damage with impaired physical function in rheumatoid arthritis: a ten-year, longitudinal observational study in 238 patients.

OBJECTIVE: To investigate the longitudinal relationship between physical disability, disease activity, and radiographic damage over 10 years in patients with rheumatoid arthritis (RA). METHODS: A cohort of 238 consecutively enrolled RA patients from the European Research on Incapacitating Disease and Social Support study (age range 20-70 years, mean disease duration 2.3 years, 68% rheumatoid factor [RF] positive) was followed up longitudinally for 10 years. Assessments at baseline and at years 1, 2, 5, and 10 comprised review of demographic variables, measurement of disease activity with the erythrocyte sedimentation rate (ESR), functional evaluations using the Health Assessment Questionnaire (HAQ) and grip strength (average value of the right and left hand), and radiographs of the hands scored by the van der Heijde modification of the Sharp method. Marginal modeling by generalized estimating equations was used to study the longitudinal relationship between the ESR and modified Sharp radiographic damage score with respect to explaining the HAQ score and grip strength. Age, sex, RF status, and disease duration were entered as covariates. RESULTS: The HAQ score and grip strength were longitudinally associated with the momentary modified Sharp/van der Heijde score as well as with progression in this score, independent of the ESR. Therefore, an increase of 10 units in the modified Sharp/van der Heijde score will result in a 0.03-unit increase in HAQ score and a 0.95-kg decrease in grip strength, after adjustment for the ESR. CONCLUSION: This 10-year observational study provides evidence that both radiographic damage and disease activity are independent contributors to impaired physical function in RA, both early and late in the disease process.