Age modifies the prognostic relevance of extracellular water-to-total body water ratio in rheumatoid arthritis: a retrospective cohort study.

BACKGROUND

Clinicians often recognise broader deterioration in a patient's overall condition that is not fully captured by conventional disease-specific measures. Ageing is associated with reduced physiological reserve and altered body fluid distribution. However, objective markers that capture these changes remain limited. Because the extracellular water-to-total body water ratio (ECW/TBW) reflects fluid distribution, we hypothesised that its prognostic relevance is age-dependent rather than uniform.

METHODS

In this retrospective cohort study, 186 adults with rheumatoid arthritis underwent bioelectrical impedance analysis in 2017 and were followed until December 2025. The primary outcome was a composite of all-cause death or transition to do-not-attempt-resuscitation/best supportive care (DNAR/BSC) status. Cox proportional hazards models including an age × ECW/TBW interaction term were used. Age-stratified analyses used the cohort median age (68 years).

RESULTS

During a median follow-up of 95.2 months, 17 participants experienced death or transition to DNAR/BSC status. Age was strongly associated with risk (HR per 10-year increase 2.53, 95% CI 1.47-4.34; p < 0.001). In age-adjusted models, ECW/TBW was not independently associated with the outcome (HR per 0.01 increase 1.10, 95% CI 0.88-1.37; p = 0.40). In contrast, the age × ECW/TBW interaction was significant (HR 1.22, 95% CI 1.05-1.42; p = 0.010), suggesting that the association between ECW/TBW and the outcome differed according to age. Elevated ECW/TBW was associated with higher risk among older participants (HR 3.10, 95% CI 1.21-8.63; p = 0.018), but not among younger individuals. In competing-risk analyses, elevated ECW/TBW was associated with a higher cumulative incidence of non-planned admissions among older participants (Gray's test p = 0.014).

CONCLUSIONS

The prognostic relevance of ECW/TBW appeared to vary by age, emerging primarily in later life rather than functioning as a uniform risk marker. These exploratory findings suggest that ECW/TBW may reflect aspects of age-related physiological vulnerability and may help identify older individuals at increased risk of non-planned hospitalisations and other unstable clinical trajectories. As a simple non-invasive measure, ECW/TBW may complement disease activity-centred assessment, although external validation is required.