Association Between Systemic Inflammation Response Index (SIRI) and Cardiovascular Disease Mortality in Individuals with Anemia: Findings from NHANES 1999–2018

Background: Cardiovascular disease (CVD) is a leading cause of mortality in individuals with anemia. This study investigates the association between the Systemic Inflammation Response Index (SIRI) and CVD mortality in this population. Methods: Data from 3,212 participants with confirmed anemia from the NHANES 1999–2018 were analyzed. Participants were stratified by SIRI levels. Univariate and multivariate Cox regression analyses assessed the relationship between SIRI and CVD mortality, with subgroup analyses for various demographic and clinical factors. Results: Higher SIRI levels were associated with older age, male gender, and increased prevalence of chronic conditions, such as chronic kidney disease, diabetes, and hypertension. CVD mortality was significantly higher in the highest SIRI group (15.7%) compared to the lowest (4.9%, p < 0.001). SIRI was a significant predictor of CVD mortality (HR: 1.3, 95% CI: 1.25–1.36, p < 0.001). Participants in the highest SIRI quartile had a markedly increased risk (HR: 4.24, 95% CI: 2.96–6.07, p < 0.001). A non-linear relationship was observed with a threshold at SIRI 0.244, above which the risk steeply increased (HR: 4.807, 95% CI: 2.945–7.845, p < 0.001). Conclusions: Higher SIRI levels are strongly associated with increased CVD mortality in individuals with anemia, with a non-linear relationship. These findings highlight the role of systemic inflammation in CVD risk, suggesting that SIRI may be a valuable biomarker in this population.