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.