Dynamic and Static Effects of the Systemic Inflammatory Response Index on All‐Cause Mortality in Individuals With Atherosclerotic Cardiovascular Disease: Evidence From National Health and Nutrition Examination Survey

<b>Objective:</b> This research focuses on analyzing the link between the systemic inflammatory response index (SIRI) and all-cause mortality in individuals with atherosclerotic cardiovascular disease (ASCVD) . <b>Methods:</b> This research analyzed data from 4693 patients using nine cycles of the National Health and Nutrition Examination Survey (NHANES). The connection between SIRI and mortality was determined by employing survey-weighted Cox models, with hazard ratios (HRs) and 95% confidence intervals (CIs) being computed. Kaplan-Meier method illustrated survival differences across SIRI levels. Sensitivity analyses involved restricted cubic splines (RCS), stratified analysis, and <i>E</i>-value calculations. Landmark analysis assessed survival differences at multiple follow-up intervals, while time-dependent receiver operating characteristic curves evaluated SIRI's prognostic value. Mediation analysis identified potential intermediaries impacting the SIRI-mortality relationship. <b>Results:</b> Over 406,564 person-months, 1933 deaths occurred. Adjusted Cox models discovered that higher SIRI was connected with elevated overall mortality [HR 1.192, (95% CI 1.131-1.256), <i>p</i> < 0.001]. Higher SIRI consistently showed lower survival probabilities. RCS and stratified analysis confirmed the robustness of these findings. Survival probability at different follow-up periods was considerably lower in those with higher SIRI. Additionally, SIRI demonstrated a prognostic value of 0.66 for all-cause mortality at 1 year and 3 years, and 0.65 at 5 years. Notably, serum uric acid (6.2%) partially mediated the connection between SIRI and mortality from all causes. <b>Conclusion:</b> In ASCVD patients, SIRI was robustly correlated with all-cause mortality, partially mediated by serum uric acid.