Use of the Behavioral Regulation in Exercise Questionnaire-2 to assess motivation for physical activity in persons with rheumatoid arthritis: an observational study.

Arthritis patients may show little motivation for physical activity (PA), resulting in a sedentary lifestyle. The primary objective of the study was to investigate whether motivation for PA and fulfillment of PA recommendations were associated with cardiorespiratory fitness in patients with RA. The exploratory objective was to study whether university students could be used as controls for RA patients in future studies of PA motivation. Peak oxygen uptake (VO2peak) was measured in 93 RA patients. The patients and 354 students filled in the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2). Data were analyzed using structural equation modeling with adjustment for age and sex. The BREQ-2 scores were also compiled to an overall motivational style "Relative Autonomy Index" as previously published. Mean VO2peak for the RA patients was 32.2 (SD: 9.6) mL × min-1 × kg-1. Only 29 patients (31%) fulfilled the current recommendations for PA. BREQ-2 scores were associated with measured VO2peak (standardized coefficient 0.33, p < 0.001). Whether a person fulfilled the current recommendations for PA was a significant mediator of this effect (standardized coefficients: mediated effect; 0.22, p = 0.001, remaining direct effect; 0.11, p = 0.18). The Relative Autonomy Index also significantly predicted measured VO2peak (standardized coefficient 0.30, p < 0.001). The underlying BREQ-2 factor structure was significantly different between RA patients and university students, and comparison of scores would not be adequate. Motivation for PA was significantly associated with measured VO2peak in RA patients. The effect was mediated by whether the patient fulfilled the current recommendations for PA. Addressing and stimulating motivation is important when intervening to increase PA and cardiovascular fitness in RA patients.

Faster age-related decline in cardiorespiratory fitness in rheumatoid arthritis patients: an observational study in the Trøndelag Health Study.

Primary aim: Compare change in estimated cardiorespiratory fitness (eCRF change) in rheumatoid arthritis (RA) patients with population-based age- and sex-matched controls during ~ 11-year follow-up and identify variables associated with eCRF change. Secondary aim: Compare eCRF level in RA patients and controls. eCRF change from the second (HUNT2 1995-1997) to the third (HUNT3 2006-2008) surveys of the Norwegian Trøndelag Health Study was compared between RA patients (n = 188) and controls (n = 26,202) attending both surveys. Predictors of eCRF change were identified by Lasso regression followed by multiple linear regression. Mean eCRF level in RA patients (n = 436) and controls (n = 67,910) was compared using age-adjusted linear regression stratified on sex, as well as two-sample t tests including RA patients (n = 432) and controls (n = 59,124) who attended either HUNT2, HUNT3 or both HUNT2 and HUNT3. The mean eCRF decline from HUNT2 to HUNT3 in RA patients was 8.3 mL min-1 kg-1 versus 6.7 mL min-1 kg-1 in controls (p < 0.001). The decline was faster in RA patients and larger with higher baseline age (standardized regression coefficient for RA patients: (- 0.482 × age + 0.044); controls: (- 0.367 × age, p < 0.001). The decline was also associated with smoking, cardiovascular disease, increasing body mass index, asthma, and hypertension. Mean differences in age-adjusted eCRF level for RA patients versus controls (p < 0.001): women HUNT2: - 3.2 mL min-1 kg-1; HUNT3: - 5.0 mL min-1 kg-1; men HUNT2: - 1.8 mL min-1 kg-1; HUNT3: - 4.0 mL min-1 kg-1. Higher age at baseline was associated with faster decline in eCRF. This change was more pronounced in RA patients than controls, indicating a larger negative effect on fitness of aging in RA. RA patients had lower eCRF compared to healthy individuals.

Relative importance of inflammation and cardiorespiratory fitness for all-cause mortality risk in persons with rheumatoid arthritis: the population-based Trøndelag Health Study.

OBJECTIVE: Inflammation and reduced cardiorespiratory fitness (CRF) are associated with increased mortality rates in rheumatoid arthritis (RA). We aimed at directly comparing the relative importance of inflammation and reduced CRF as mediators of all-cause mortality in persons with RA compared with controls, quantifying direct and indirect (mediated) effects. METHODS: Persons with (n=223, cases) and without (n=31 684, controls) RA from the third survey of the Trøndelag Health Study (HUNT3, 2006-2008) were included. Inflammation was quantified using C reactive protein (CRP) and estimated CRF (eCRF) was calculated using published formulae. All-cause mortality was found by linkage to the Norwegian Cause of Death Registry, with follow-up from inclusion in HUNT3 until death or 31 December 2018. Data were analysed using standardised equation modelling, permitting complex correlations among variables. RESULTS: Persons with RA had increased all-cause mortality rates (24.1% vs 9.9%, p<0.001). Both eCRF (p<0.001) and CRP ≥3 mg/L (p<0.001) were mediators of this excess mortality, rendering the direct effect of RA non-significant (p=0.19). The indirect effect of RA mediated by eCRF (standardised coefficient 0.006) was approximately three times higher than the indirect effect mediated by CRP (standardised coefficient 0.002) in a model adjusted for other mortality risk factors. CONCLUSION: Even with CRP concentrations <3 mg/L in all patients with RA, excess mortality mediated by low CRF would still play an important role. Improved inflammation control in RA does not necessarily lead to better CRF. Therefore, our study strongly supports recommendations for development and implementation of exercise programmes aimed at improving CRF in persons with RA.

Inflammation mediates approximately one quarter of excess relative all-cause mortality in persons with rheumatoid arthritis: the Trøndelag Health Study.

Inflammation may contribute to excess mortality in rheumatoid arthritis (RA) patients. We investigated associations to all-cause mortality of the inflammation markers high-sensitivity C-reactive protein (CRP), lactoferrin (neutrophil activation marker), and neopterin (monocyte activation marker). From the population-based Trøndelag Health Study (3rd wave 2006-2008), 316 RA patients and 43,579 controls were included. Lactoferrin and neopterin were quantified in a nested cohort (n = 283 RA patients, n = 3698 controls). Follow-up was until death found by linkage to the Norwegian Cause of Death Registry or 31.12.2018. All-cause mortality was analyzed using Cox regression and Cox regression-based mediation analysis. Having RA (hazard ratio (HR): 1.25, 95%CI: 1.00, 1.56, p = 0.048), and CRP ≥ 3 mg/L (HR: 1.50, 95%CI: 1.41, 1.60, p < 0.001) were associated with all-cause mortality. The overall excess relative mortality risk of having RA was 38%. CRP ≥ 3 mg/L mediated approximately 1/4 of this risk (p < 0.001). In the nested cohort, CRP ≥ 3 mg/L (HR: 1.51, 95%CI: 1.26, 1.80, p < 0.001) and neopterin (HR: 1.17, 95%CI: 1.01, 1.36, p = 0.031) were associated with all-cause mortality. In conclusion, CRP levels ≥ 3 mg/L mediated approximately a quarter of the 38% excess relative all-cause mortality risk associated with RA. Using definitions of RA remission with emphasis both on joint status and the level of general inflammation may help guide the most efficient treatment regimens.

Reduced cardiorespiratory fitness is a mediator of excess all-cause mortality in rheumatoid arthritis: the Trøndelag Health Study.

OBJECTIVES: Investigate if low cardiorespiratory fitness (CRF) was associated with and acted as a mediator of excess all-cause mortality rate in persons suffering from rheumatoid arthritis (RA) compared with the general population. METHODS: All-cause mortality was analysed using Cox regression modelling in patients with RA (n=348) and controls (n=60 938) who took part in the second (1995-1997) and third (2006-2008) waves of the longitudinal population-based Trøndelag Health Study in Norway. A mediation analysis was performed to investigate if excess relative risk of mortality in RA was mediated by low estimated CRF (eCRF). RESULTS: During the follow-up until 31 December 2018 (mean 19.3 years), the mortality rate among patients with RA (n=127, 36.5%) was higher than among controls (n=12 942, 21.2%) (p<0.001). Among controls and patients with RA, 51% and 26%, respectively, had eCRF above the median for their age and sex (p<0.001). The final Cox model included RA status and eCRF, adjusted for hypertension, body mass index, smoking, cholesterol, diabetes and creatinine. eCRF below median for sex and age category was associated with increased mortality (p<0.001). The total excess relative risk of mortality in patients with RA was 28% (95% CI 2% to 55%, p=0.035), in which RA itself contributed 5% and the direct and indirect contributions of low eCRF accounted for 23%. CONCLUSIONS: Low eCRF was an important mediator of the increased all-cause mortality rate found in RA. Our data indicate that patients with RA should be given advice to perform physical activity that increases CRF, along with optimised treatment with antirheumatic drugs, from the time of diagnosis.

An Estimation Model for Cardiorespiratory Fitness in Adults with Rheumatoid Arthritis.

PURPOSE: Cardiopulmonary exercise testing of peak oxygen uptake (V˙O2peak) is the gold standard to measure cardiorespiratory fitness (CRF). For resource-intensive evaluation, equations estimating CRF (eCRF) may be used. The purpose was to investigate if an eCRF equation from a healthy population is useful in persons with rheumatoid arthritis (RA), and if necessary, develop new equations for eCRF in this group. METHODS: V˙O2peak results from 93 persons with RA were compared with eCRF calculated by an established equation for healthy individuals including age, sex, physical activity (PA index), resting HR (RHR), and waist circumference. Because of deviation from the observed V˙O2peak, new equations for eCRF in persons with RA were developed from regression analysis of variables associated with observed V˙O2peak. RESULTS: The established equation overestimated CRF (R = 0.48, root mean square error [RMSE] = 7.07). The new RA equation more accurately estimated CRF (R = 0.81, RMSE = 4.44) (female = 0, male = 1; never smoked = 0, ever smoked = 1): eCRF = 77.961 + (sex × 28.791) - (age × 0.358) - (age-sex interaction × 0.326) - (body mass index [BMI] × 0.700) - (RHR × 0.125) - (smoking × 1.854) + (PA index × 0.211) - (patient global RA assessment × 0.071). Alternative new RA equation (R = 0.79, RMSE = 4.63): eCRF = 77.851 + (sex × 25.460) - (age × 0.381) - (age-sex interaction × 0.254) - (BMI × 0.743) - (RHR × 0.115) - (smoking × 2.154) + (PA index × 0.209). CONCLUSIONS: The new RA equations better predicted CRF in individuals with RA, preventing overestimation in low-fit persons. The new equation should be preferred when estimating CRF in individuals with RA. The alternative equation, without patient global assessment, is useful for individuals with RA in population-based studies.

Cardiorespiratory fitness in patients with rheumatoid arthritis is associated with the patient global assessment but not with objective measurements of disease activity.

Objective: Patients with rheumatoid arthritis (RA) suffer from more cardiovascular disease (CVD), and develop cardiovascular risk factors at an earlier age than the general population. Cardiorespiratory fitness (CRF) is an important predictor of cardiovascular health. There are few data regarding CRF of RA patients, measured as peak oxygen uptake (VO2peak) by the gold standard method; cardiopulmonary exercise testing. We compared CRF in RA patients to those from a healthy population, and investigated if risk factors for CVD and RA-specific variables including subjective and objective disease activity measures were associated with CRF in RA patients. Methods: VO2peak tests of RA patients (n=93) were compared to those of an age-matched and gender-matched healthy population (n=4631) from the Nord-Trøndelag Health Study. Predictors of VO2peak were found using Lasso (least absolute shrinkage and selection operator) regression, followed by standardised multiple linear regression. Results: Women with RA ≥40 years and men with RA aged 40-49 years or 60-69 years had up to 20% lower CRF than the healthy population in the same age groups. By relative importance, body mass index (standardised coefficient=-0.25, p<0.001), physical activity level (coefficient=0.21, p<0.001), patient global assessment (PGA; coefficient=-0.14, p=0.006), systolic blood pressure (coefficient=-0.12, p=0.016), resting heart rate (coefficient=-0.11, p=0.032) and smoking (coefficient=-0.10, p=0.046) were significant predictors of CRF (R2=0.82, gender-adjusted and age-adjusted). Conclusion: CRF in RA patients was lower than in a healthy population. CRF was associated with common risk factors for CVD and the PGA score. Focusing on fitness in RA patients may improve cardiovascular health.