Comparative value of novel inflammatory indices in predicting incident carotid atherosclerosis: SIRI outperforms other markers in a general population

Background Systemic inflammation is a core driver of carotid atherosclerosis (CAS). Although various inflammatory indices derived from routine blood tests have been associated with prevalent CAS, most existing evidence is limited to cross-sectional designs, and a systematic head-to-head comparison of their predictive value is lacking. This study aimed to bridge this gap by evaluating the associations of six composite inflammatory indices with the risk of incident CAS to identify the optimal predictive marker. Methods We conducted a prospective cohort study comprising 12,289 participants free of CAS at baseline from a health screening center in Beijing. Six inflammatory indices—Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Systemic Immune-Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), Aggregate Index of Systemic Inflammation (AISI), and Neutrophil Percentage-to-Albumin Ratio (NPAR)—were calculated based on baseline data. Cox proportional hazards models, restricted cubic splines, and Random Survival Forest (RSF) models were utilized to assess associations and predictive performance. Mediation analysis was performed to investigate the role of Body Mass Index (BMI). Results During follow-up, 2,432 (19.8%) participants developed CAS. After multivariable adjustment, all six inflammatory indices were independently associated with an increased risk of CAS. Among them, SIRI demonstrated the most robust predictive value; participants in the highest quartile of SIRI had a 46% higher risk compared to those in the lowest quartile (Hazard Ratio [HR] = 1.46, 95% Confidence Interval [CI]: 1.30–1.64, P < 0.001). RSF analysis confirmed the superior predictive importance of SIRI. Notably, a significant sex interaction was observed ( P for interaction = 0 .031), with a more pronounced association found in men. Furthermore, mediation analysis revealed that BMI partially mediated this association. Conclusion Our findings identify SIRI as a robust and independent predictor of CAS development, outperforming other common inflammatory indices. As a readily available and cost-effective biomarker, SIRI offers significant potential for enhancing early risk stratification for subclinical atherosclerosis in clinical practice.