Effects of age and sex on all-cause mortality among NHANES participants with metabolic syndrome and rheumatoid arthritis.

BACKGROUND

Epidemiological studies have established a strong association between metabolic syndrome (MetS), rheumatoid arthritis (RA), and increased risk of cardiovascular disease (CVD) and all-cause mortality. However, comprehensive data evaluating the influence of age and sex on all-cause mortality among patients diagnosed concurrently with these conditions remain limited.

METHODS

Data from 1,290 adults diagnosed with both MetS and RA were obtained from nine cycles of the NHANES database (2001–2018). Associations between age, sex, and their subgroups with mortality risk were assessed using Cox proportional hazards models adjusted for complex survey weighting. Analyses included unadjusted, partially adjusted, and fully adjusted models. Additional analytical methods included restricted cubic spline (RCS) modeling, Kaplan–Meier survival analysis, E-value sensitivity testing, and the Boruta algorithm to rank predictor importance.

RESULTS

Individuals aged ≥ 65 years demonstrated a significantly higher risk of all-cause mortality compared to younger participants (HR = 3.32, 95% CI: 2.03–5.44; p < 0.001). Overall, males exhibited significantly greater all-cause mortality than females (HR = 1.98, 95% CI: 1.15–3.43; p = 0.014). Interaction analysis revealed an additive interaction between age and sex. Older females had a 4.16-fold greater mortality risk compared with younger females (95% CI: 2.18–7.95; p < 0.001), whereas older males exhibited a 6.88-fold increased risk (95% CI: 3.63–13.02; p < 0.001). RCS analysis confirmed a linear association between age and all-cause mortality, indicating incremental risk with advancing age. Kaplan–Meier survival curves revealed the lowest survival probability among older males and the highest among younger females. E-value sensitivity analysis confirmed the robustness of these findings. The Boruta algorithm ranked age and sex as the most influential predictors of all-cause mortality. Subgroup analyses, proportional hazards assumption checks, and multicollinearity diagnostics further supported the reliability of these results.

CONCLUSION

This study is the first to demonstrate a significant additive interaction between advanced age and sex among individuals with concurrent MetS and RA, substantially amplifying all-cause mortality risk. Mortality risk rose incrementally with age, particularly in males, providing critical evidence for stratified risk assessment and targeted interventions within this vulnerable patient population.