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.