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Long-Term Physical Activity and Subsequent Risk for Rheumatoid Arthritis Among Women: A Prospective Cohort Study.

ABSTRACT: OBJECTIVE:To evaluate the effects of long-term physical activity on subsequent risk of rheumatoid arthritis (RA) in a prospective cohort study. METHODS:This study investigated physical activity and RA risk among women from the Nurses' Health Study II (1989-2015). Physical activity exposures and covariates were prospectively obtained using biennial questionnaires. Two rheumatologists independently reviewed the medical records of women who self-reported a new diagnosis of RA on biennial questionnaires and who screened positive for RA based on a supplemental survey. All incident RA cases met the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA. The primary analysis investigated the long-term cumulative average number of hours spent in recreational physical activity 2-8 years prior to the RA diagnosis, a time span chosen to reduce the potential for reverse causation bias, since early RA affects physical activity prior to diagnosis. Estimated Cox regression hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the risk of RA serologic phenotypes (all, seropositive, or seronegative) in relation to physical activity categories. The analyses were adjusted for body mass index (BMI) at age 18 years and time-varying potential confounders, and the mediating effect of updated BMI on the interaction between physical activity and RA risk was quantified. RESULTS:Among the 113,366 women analyzed, 506 incident RA cases (67.0% with seropositive RA) were identified during 2,428,573 person-years of follow-up. After adjustment for confounders, including smoking, dietary quality, and BMI at age 18 years, increasing cumulative average total hours of recreational physical activity was associated with a reduced risk of RA, as follows: HR 1.00 for <1 hour/week (reference), HR 1.00 (95% CI 0.78-1.29) for 1 to <2 hours/week, HR 0.92 (95% CI 0.72-1.17) for 2 to <4 hours/week, HR 0.84 (95% CI 0.63-1.12) for 4 to <7 hours/week, and HR 0.67 (95% CI 0.47-0.98) for ?7 hours/week (P for trend = 0.02). The proportion of the effect between physical activity and RA mediated by updated BMI was 14.0% (P = 0.002) for all RA and 20.0% (P = 0.001) for seropositive RA. CONCLUSION:Higher levels of physical activity were associated with reduced RA risk. These results add to the literature implicating metabolic factors in the pathogenesis of RA.

SUBMITTER: Liu X

PROVIDER: S-EPMC6717001 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Long-Term Physical Activity and Subsequent Risk for Rheumatoid Arthritis Among Women: A Prospective Cohort Study.

Liu Xinyi X Tedeschi Sara K SK Lu Bing B Zaccardelli Alessandra A Speyer Cameron B CB Costenbader Karen H KH Karlson Elizabeth W EW Sparks Jeffrey A JA

Arthritis & rheumatology (Hoboken, N.J.) 20190719 9

<h4>Objective</h4>To evaluate the effects of long-term physical activity on subsequent risk of rheumatoid arthritis (RA) in a prospective cohort study.<h4>Methods</h4>This study investigated physical activity and RA risk among women from the Nurses' Health Study II (1989-2015). Physical activity exposures and covariates were prospectively obtained using biennial questionnaires. Two rheumatologists independently reviewed the medical records of women who self-reported a new diagnosis of RA on bien ...[more]

PMID: 30920773

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Project description:Background/Purpose: Prior studies show an independent association between greater physical activity and lower inflammatory markers among adults in the general population, but the impact of physical activity on systemic inflammation in people with rheumatoid arthritis (RA) hasn’t been thoroughly investigated. We therefore aimed to determine whether physical activity behavior associates with differential expression of inflammatory genes in RA. Methods: Data derive from baseline assessments for a prospective observational cohort of patients with RA. At each study visit, we obtained detailed clinical information, collected peripheral whole blood for subsequent RNA sequencing (RNA-seq), and provided participants with actigraphs (GT9X ActiGraph Link device) to objectively measure physical activity by wearing the device at home for 7 consecutive 24-hour periods. Participants were categorized into three physical activity groups based on the highest (“active”), middle (“intermediate”), and lowest (“inactive”) tertiles for percentage of time spent in moderate/vigorous physical activity (metabolic equivalent (MET) level ≥2.00) across the sample. Results: There were 35 patients with complete clinical, actigraphy, and transcriptomic data available for analysis. The participants had a mean age of 56 years, were 90% female, and self-reported the following racial/ethnic identities: 32% white, 11% African American, 8% Asian, 40% Hispanic. Participants spent 48%, 41%, and 12% of time awake in sedentary, light, and moderate physical activity, respectively. None of the participants achieved vigorous activity. The patients in the most active group were younger but did not otherwise significantly differ by clinical and demographic characteristics compared to the other physical activity groups. However, in the differential gene expression analysis comparing the highest versus lowest physical activity tertiles, there were 365 up- and 402 down-regulated genes at an adjusted P value < 0.1. Gene set enrichment analysis revealed that the most physically active patients exhibited downregulation of diverse innate and adaptive immune signaling pathways. Assessment of upstream cytokine activation states demonstrated inhibition of type I, II and III interferons and activation of EPO in the highest physical activity tertile patients. Conclusion: Among a racially and ethnically diverse RA cohort, participants who spent more time in moderately intense physical activity had down-regulation of genes involved in both innate and adaptive immune signaling compared to those who were more sedentary. These findings provide mechanistic evidence to support a disease-modifying effect of physical activity in RA.

Project description:BackgroundUncertainty remains concerning association between long-term physical activity and incident type 2 diabetes mellitus (DM). We intended to evaluate physical activity participation over a 6-year span and assess association with subsequent 10-year incident DM risk, as well as examine mediation role by obesity.MethodsA total of 9757 community-dwelling adults aged ≥ 50 years in England were included in the population-based cohort. Physical activity participation, including trajectories and cumulative participation were assessed using weighted Z score over a 6-year span from wave 1 (2002-2003) to wave 4 (2008-2009). Incident DM recorded over a 10-year span from wave 4 (2008-2009) to wave 9 (2018-2019) was outcome.Results5 distinct activity trajectories were identified, including persistently low (N=3037, incident DM=282), initially low then improving (1868, 90), initially high then declining (325, 20), persistently moderate (2489, 170), and persistently high (2038, 108). Compared with persistently low, participants of initially low then improving, persistently moderate and high were associated with lower incident DM risk, with multivariable-adjusted hazard ratios (HR) of 0.41 (95% confidence interval [CI]: 0.32 to 0.53, P<0.001), 0.70 (95% CI: 0.56 to 0.89, P=0.004) and 0.49 (95% CI: 0.37 to 0.65, P <0.001), respectively. Elevated cumulative activity was also associated with lower DM risk, with each quintile increment in cumulative weighted Z score corresponding to HR of 0.76 (95% CI: 0.71 to 0.82, P <0.001). Mediation analysis found that body mass index, waist circumference and change in body mass index mediate 10% (P <0.001), 17% (P <0.001) and 9% (P <0.001) of the observed association between activity and incident DM, respectively.ConclusionsFor middle aged and older adults, both gradually improved and persistently active participation in physical activity were associated with subsequent lower risk of incident DM, with obesity playing a potential mediator. Strategies focusing on improving and maintaining active participation in physical activity might be beneficial from DM prevention perspective.

Project description:ObjectiveTo evaluate rheumatoid arthritis (RA) disease activity and risk of RA-associated interstitial lung disease (RA-ILD).MethodsWe investigated disease activity and risk of RA-ILD using the Brigham RA Sequential Study (BRASS, 2003-2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA-ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA-ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA-ILD, using annually updated DAS28 data, with adjustment for known RA-ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules.ResultsAmong 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA-ILD during a mean ± SD follow-up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28-3.82) for RA-ILD compared to the remission/low disease activity group. Risk of RA-ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61-3.28) for low disease activity, 2.08 (95% CI 1.06-4.05) for moderate disease activity, and 3.48 (95% CI 1.64-7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA-ILD increased by 35% (95% CI 14-60%). Results were similar in analyses that included follow-up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules.ConclusionActive articular RA was associated with an increased risk of developing RA-ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA-ILD development.

Dataset Information

Long-Term Physical Activity and Subsequent Risk for Rheumatoid Arthritis Among Women: A Prospective Cohort Study.

Publications

Long-Term Physical Activity and Subsequent Risk for Rheumatoid Arthritis Among Women: A Prospective Cohort Study.

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