Systemic inflammation markers independently associated with increased mortality in individuals with hyperuricemia: Results from the NHANES prospective cohort study

Abstract

Background

Hyperuricemia is associated with increased systemic inflammation. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are novel systemic inflammation markers and prognostic markers. However, no studies have evaluated the association between the SII/SIRI and mortality risk in individuals with hyperuricemia. This study aimed to investigate the predictive value of the SII and SIRI for all-cause and cardiovascular mortality in a large cohort of hyperuricemia patients.

Methods

We conducted a prospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2020. Hyperuricemia was defined as serum uric acid (SUA) levels of ≥7 mg/dL in men and ≥6 mg/dL in women. The SII and SIRI were calculated based on complete blood count parameters. Associations with all-cause and cardiovascular mortality were analyzed using Cox proportional hazards models. Nonlinearity and effect modification were assessed using restricted cubic splines (RCS) and interaction analysis.

Results

Among the 6181 participants with hyperuricemia aged 20 years and older, over a total 181 months of follow-up, there were 936 all-cause deaths, of which 195 were cardiovascular mortality. In the fully adjusted models, the hazard ratios (HRs) were 1.73 (95% CI 1.42-2.13) for the SII and 2.18 (95% CI 1.82-2.62) for the SIRI with all-cause mortality. The adjusted HRs were 2.08 (95% CI 1.37-3.14) for the SII and 2.32 (95% CI 1.56-3.45) for the SIRI with cardiovascular mortality. Spline models identified nonlinear U-shaped (SII) and J-shaped (SIRI) relationships of inflammation markers with mortality.

Conclusions

Elevated SII and SIRI are independent predictors of mortality in hyperuricemia patients. These inflammatory biomarkers may improve risk stratification in this high-risk population. Further research should evaluate utility in guiding preventive interventions.