Association of the Systemic Immune-inflammation Index with All-cause and Cardiovascular Mortality in Individuals with Rheumatoid Arthritis

The systemic immune-inflammation index (SII), a metric reflecting systemic inflammatory response and immune activation, remains underexplored concerning its correlation with mortality among rheumatoid arthritis (RA) patients. This study aimed to delineate the association between SII and both all-cause and cardiovascular mortality within the cohort of American adults diagnosed with RA, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The investigation extracted data from NHANES cycles between 1999 and 2018, identifying RA patients through questionnaire responses. The SII was computed based on complete blood counts, employing the formula: (platelets × neutrophils) / lymphocytes. The optimal SII cutoff value for significant survival outcomes was determined using maximally selected rank statistics. Multivariable Cox proportional hazards models assessed the relationship between SII levels and mortality (all-cause and cardiovascular) among RA patients, with subgroup analyses examining potential modifications by clinical confounders. Additionally, restricted cubic spline (RCS) analyses were conducted to explore the linearity of the SII-mortality association. The study encompassed 2070 American adults with RA, among whom 287 exhibited a higher SII (≥ 919.75) and 1783 a lower SII (< 919.75). Over a median follow-up duration of 108 months, 602 participants died. After adjustments for demographic, socioeconomic, and lifestyle variables, a higher SII was associated with a 1.48-fold increased risk of all-cause mortality (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.21-1.81, P < 0.001) and a 1.51-fold increased risk of cardiovascular mortality (HR = 1.51, 95% CI 1.04-2.18, P = 0.030) compared to a lower SII. Kaplan-Meier analyses corroborated significantly reduced survival rates within the higher SII cohort for both all-cause and cardiovascular mortality (P < 0.0001 and P = 0.0004). RCS analyses confirmed a positive nonlinear relationship between SII and mortality rates. In conclusion, the SII offers a straightforward indicator of the equilibrium between detrimental innate inflammation and beneficial adaptive immunity. Our investigation, utilizing a comprehensive and nationally representative sample, reveals that elevated SII levels independently forecast a greater risk of mortality from all causes, as well as cardiovascular-specific mortality, in individuals suffering from RA. These insights underscore the clinical relevance of the SII as an affordable and readily accessible biomarker. Its incorporation into regular clinical practice could significantly enhance the precision of risk assessment and forecasting for patients with RA, facilitating more tailored and effective management strategies. Specifically, patients with high SII levels could be identified for more stringent cardiovascular risk management, including closer monitoring, lifestyle interventions, and aggressive pharmacological treatments to mitigate their increased risk of mortality.