PT  - JOURNAL ARTICLE
AU  - Videm, Vibeke
AU  - Liff, Marthe Halsan
AU  - Hoff, Mari
TI  - Relative importance of inflammation and cardiorespiratory fitness for all-cause mortality risk in persons with rheumatoid arthritis: the population-based Trøndelag Health Study
AID  - 10.1136/rmdopen-2023-003194
DP  - 2023 Aug 01
TA  - RMD Open
PG  - e003194
VI  - 9
IP  - 3
4099  - http://rmdopen.bmj.com/content/9/3/e003194.short
4100  - http://rmdopen.bmj.com/content/9/3/e003194.full
SO  - RMD Open2023 Aug 01; 9
AB  - Objective Inflammation and reduced cardiorespiratory fitness (CRF) are associated with increased mortality rates in rheumatoid arthritis (RA). We aimed at directly comparing the relative importance of inflammation and reduced CRF as mediators of all-cause mortality in persons with RA compared with controls, quantifying direct and indirect (mediated) effects.Methods Persons with (n=223, cases) and without (n=31 684, controls) RA from the third survey of the Trøndelag Health Study (HUNT3, 2006–2008) were included. Inflammation was quantified using C reactive protein (CRP) and estimated CRF (eCRF) was calculated using published formulae. All-cause mortality was found by linkage to the Norwegian Cause of Death Registry, with follow-up from inclusion in HUNT3 until death or 31 December 2018. Data were analysed using standardised equation modelling, permitting complex correlations among variables.Results Persons with RA had increased all-cause mortality rates (24.1% vs 9.9%, p<0.001). Both eCRF (p<0.001) and CRP ≥3 mg/L (p<0.001) were mediators of this excess mortality, rendering the direct effect of RA non-significant (p=0.19). The indirect effect of RA mediated by eCRF (standardised coefficient 0.006) was approximately three times higher than the indirect effect mediated by CRP (standardised coefficient 0.002) in a model adjusted for other mortality risk factors.Conclusion Even with CRP concentrations <3 mg/L in all patients with RA, excess mortality mediated by low CRF would still play an important role. Improved inflammation control in RA does not necessarily lead to better CRF. Therefore, our study strongly supports recommendations for development and implementation of exercise programmes aimed at improving CRF in persons with RA.Data are available upon reasonable request. Data from the HUNT Study are available upon reasonable request from the HUNT Research Centre (https://www.ntnu.edu/hunt/data), following approval from the Regional Research Ethics Committee. However, restrictions apply to the availability of the data for the present paper, which were used under license for the current study and are not publicly available, in accordance with Norwegian law.