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

ABSTRACT: 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?-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.

SUBMITTER: Liff MH

PROVIDER: S-EPMC7835174 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Liff Marthe Halsan MH Hoff Mari M Wisløff Ulrik U Videm Vibeke V

Rheumatology international 20201009 2

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 = 2 ...[more]

PMID: 33037488

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Project description:BackgroundExercise training, including high-intensity interval training (HIIT), improves rheumatoid arthritis (RA) inflammatory disease activity via unclear mechanisms. Because exercise requires skeletal muscle, skeletal muscle molecular pathways may contribute. The purpose of this study was to identify connections between skeletal muscle molecular pathways, RA disease activity, and RA disease activity improvements following HIIT.MethodsRA disease activity assessments and vastus lateralis skeletal muscle biopsies were performed in two separate cohorts of persons with established, seropositive, and/or erosive RA. Body composition and objective physical activity assessments were also performed in both the cross-sectional cohort and the longitudinal group before and after 10 weeks of HIIT. Baseline clinical assessments and muscle RNA gene expression were correlated with RA disease activity score in 28 joints (DAS-28) and DAS-28 improvements following HIIT. Skeletal muscle gene expression changes with HIIT were evaluated using analysis of covariance and biological pathway analysis.ResultsRA inflammatory disease activity was associated with greater amounts of intramuscular adiposity and less vigorous aerobic exercise (both p < 0.05). HIIT-induced disease activity improvements were greatest in those with an older age, elevated erythrocyte sedimentation rate, low cardiorespiratory fitness, and a skeletal muscle molecular profile indicative of altered metabolic pathways (p < 0.05 for all). Specifically, disease activity improvements were linked to baseline expression of RA skeletal muscle genes with cellular functions to (1) increase amino acid catabolism and interconversion (GLDC, BCKDHB, AASS, PYCR, RPL15), (2) increase glycolytic lactate production (AGL, PDK2, LDHB, HIF1A), and (3) reduce oxidative metabolism via altered beta-oxidation (PXMP2, ACSS2), TCA cycle flux (OGDH, SUCLA2, MDH1B), and electron transport chain complex I function (NDUFV3). The muscle mitochondrial glycine cleavage system (GCS) was identified as critically involved in RA disease activity improvements given upregulation of multiple GCS genes at baseline, while GLDC was significantly downregulated following HIIT.ConclusionIn the absence of physical activity, RA inflammatory disease activity is associated with transcriptional remodeling of skeletal muscle metabolism. Following exercise training, the greatest improvements in disease activity occur in older, more inflamed, and less fit persons with RA. These exercise training-induced immunomodulatory changes may occur via reprogramming muscle bioenergetic and amino acid/protein homeostatic pathways.Trial registrationClinicalTrials.gov , NCT02528344 . Registered on 19 August 2015.

Dataset Information

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

Publications

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

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