Low estimated cardiorespiratory fitness (CRF) has been shown to be an important mediator of the increased all-cause mortality rate reported among patients with rheumatoid arthritis (RA). Data derived from the second wave (HUNT2) and third wave (HUNT3) of the longitudinal, population-based Trøndelag Health Study — conducted in the northern region of Trøndelag County in Norway — were used to examine all-cause mortality in patients with RA. Results of the analysis were published in the journal RMD Open.

Recognizing that low CRF is independently associated with all-cause mortality in the general population, the researchers sought to explore whether low CRF is linked to and acts as a mediator of excess all-cause mortality in individuals with RA. The current study used Cox regression modeling to analyze all-cause mortality in 348 patients with RA and 60,938 control patients who participated in wave 2 (1995 to 1997) and wave 3 (2006 to 2008) of  the Trøndelag Health Study.

Of the 348 participants with RA, 71.0% were seropositive, 26.7% were seronegative, and 2.3% had an unknown serologic status. Among these 3 groups of patients, RA disease duration of less than 3 years, 4 to 9 years, and 10 years or longer was 27.9%, 49.7%, and 19.8%, respectively. The mean patient follow-up was 19.3 years, during which time 13,069 participants died.

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The all-cause mortality rate was significantly higher among patients with RA compared with control group participants (36.5% vs 21.2%, respectively; P <.001). In control group participants and in patients with RA, 51% and 26%, respectively, had baseline estimated CRF above the median for their age and sex (P <.001). Estimated CRF that was below the median for an individual’s sex and age category was associated with increased mortality (P <.001). The total excess relative risk for mortality was 28% (95% CI, 2% to 55%; P =.035) in patients with RA, with RA itself contributing 5% and the direct and indirect contributions of low estimated CRF accounting for 23% of this relative risk.

Low fitness was strongly associated with mortality in both arms. Of the 127 patients with RA who died, 4% of them belonged to the high-fitness category, as opposed to 8.8% of the control group participants (P =.054). The total time at risk was 1,158,878 person-years — that is, 5596 person-years for those with RA and 1,153,281 person-years for control group participants.

The investigators concluded that along with optimal medical care, a focus on the improvement and follow-up of CRF needs to be an essential part of standard treatment for RA beginning at the time of diagnosis.


Liff MH, Hoff M, Wisloff U, Videm V. Reduced cardiorespiratory fitness is a mediator of excess all-cause mortality in rheumatoid arthritis: the Trøndelag Health Study. RMD Open. 2021;7(1):e001545. doi:10.1136/rmdopen-2020-001545