The combined impact of inflammation and oxidative balance on mortality risk in rheumatoid arthritis patients: A retrospective cohort study.

Oxidative stress and systemic inflammation play pivotal roles in rheumatoid arthritis (RA) progression. However, the combined impact of oxidative balance and inflammatory status on mortality risk in RA patients remains insufficiently investigated. This study aimed to explore these potential associations. We analyzed data from 24,552 participants in the National Health and Nutrition Examination Survey (NHANES, 2007-2018). Oxidative balance was assessed using the oxidative balance score (OBS), while inflammatory status was evaluated via the systemic inflammation response index (SIRI). Cox proportional-hazards models, Kaplan-Meier survival curves, and mediation analysis were employed to examine independent and joint associations. After adjusting for confounders, each 1-point increase in the OBS was associated with a 4 % reduction in mortality (HR = 0.96, 95 % CI 0.92-1.00, P = .047), and participants in the high OBS group exhibited a 37 % lower mortality risk than those with low OBS (HR = 0.63, 95 % CI 0.42-0.94, P = .023). Whereas every 1-unit rise in the SIRI elevated the risk by 14 % (HR = 1.14, 95 % CI 1.04-1.25, P = .005), and individuals in the high SIRI group faced more than double the risk seen in their low SIRI counterparts (HR = 2.30, 95 % CI 1.18-4.49, P = .014). A potential protective effect of an antioxidant-oriented diet and lifestyle was suggested only in patients with systemic inflammation, although the association did not reach conventional statistical significance (HR = 0.59, 95% CI 0.34-1.01, P = .053). No significant benefit was observed among patients without systemic inflammation. Spearman correlation revealed a weak inverse association between OBS and SIRI (R = -0.095, P = .007). Mediation analysis confirmed that antioxidants attenuate mortality risk in RA patients by reducing inflammatory response, with a mediation proportion of 14.6% (P <.001). Antioxidants exhibit protective effects against inflammation-related mortality in RA patients, suggesting that enhancing oxidative balance may serve as a potential intervention strategy to prevent RA associated deaths.