【摘要】 目的：颈动脉粥样硬化(carotid atherosclerosis,CAS)斑块是脑卒中的独立危险因素，血管慢性炎症参与其病理过程。本研究旨在通过探讨全身免疫炎症指数(systemic immune-inflammation index,SII)与CAS的相关性，分析二者关联性的性别差异，为动脉粥样硬化早期防控提供依据。方法：研究为单中心横断面研究，选取2023年1月至12月于中南大学湘雅医院参加健康体检并完成颈动脉超声测量的成年人为研究对象，其中检出CAS者为CAS组，未检出CAS者为正常对照组。收集人口学信息、人体测量数据及实验室检查数据，按SII四分位数分为Quartile 1～4组。构建4个二元Logistic回归模型逐步校正混杂因素，分析SII与CAS的相关性，并按性别进行分层分析。采用Bootstrap法(5 000次抽样)，以白细胞、单核细胞为中介变量进行性别分层中介效应分析，通过敏感性分析验证结果稳健性。结果：共纳入19 788名研究对象，其中检出CAS患者7 567例(38.24%)。CAS组的男性占比、年龄、腰围、收缩压、舒张压、空腹血糖、白细胞计数均显著高于正常对照组(均P<0.001)；高密度脂蛋白胆固醇水平显著低于正常对照组(P<0.001)。二元Logistic回归分析显示结果存在性别异质性，在调整年龄和性别后(模型2),SII高分位(Quartile 4)组的SII与CAS风险呈显著正相关[比值比(odd ratio,OR)=1.26,95%置信区间(confidence interval,CI)1.14～1.39,P<0.01]，二者关联性在进一步调整代谢危险因素(模型3)后依然存在(OR=1.18,95%CI 1.07～1.31,P<0.01)，但在最终调整C反应蛋白、白细胞及单核细胞计数等炎症指标后(模型4)，二者关联性在总人群和男性中大幅减弱并失去统计学意义(P>0.05)；但是在女性群体中，Quartile 2组(OR=1.19,95%CI 1.02～1.39)和Quartile 4组(OR=1.20,95%CI 1.01～1.43)的SII与CAS的关联性在所有调整模型中均显著存在(均P<0.05)。中介分析结果显示，在总人群中，白细胞计数起完全中介作用(间接效应β=0.03,95%CI 0.01～0.05,P<0.01；效应占比为46.3%)，单核细胞计数则起部分中介作用(间接效应β=0.01,95%CI 0～0.02,P<0.01；效应占比为18.9%)。在男性中，炎症细胞的中介作用被显著放大，白细胞为完全中介作用(间接效应β=0.04,95%CI 0.02～0.06,P<0.01；效应占比为74.3%)，单核细胞计数起部分中介作用(间接效应β=0.01,95%CI 0～0.02,P<0.05；效应占比为24.2%)。在女性中，单核细胞(β=0,95%CI 0～0,P>0.05)和白细胞计数(β=0.01,95%CI 0～0.02,P>0.05)的中介效应无统计学意义；在调整所有混杂因素后，SII对CAS的直接效应均具有统计学意义(均P<0.05)。敏感性分析验证结果稳健。结论：SII与CAS的相关性存在显著性别异质性，高SII是女性CAS的独立关联因素，以直接效应为主，不依赖白细胞、单核细胞中介；男性中SII通过白细胞完全中介及单核细胞部分中介影响CAS。这提示SII在不同性别CAS评估中的差异化价值，为“性别靶向”筛查及干预提供数据支撑。更多还原

【Abstract】 Objective: Carotid atherosclerosis(CAS) plaques are independent risk factors for stroke, and chronic vascular inflammation is involved in their pathogenesis. This study aims to explore the association between the systemic immune-inflammation index(SII) and CAS, analyze sex-specific differences in this association, and provide evidence for the early prevention and control of atherosclerosis.Methods: This single-center cross-sectional study included adults who underwent health examinations and completed carotid ultrasound assessments at Xiangya Hospital of Central South University between January and December 2023, among whom those with CAS were classified as a CAS group, and those without CAS were classified as a normal control group. Demographic characteristics, anthropometric measurements, and laboratory data were collected. Participants were categorized into Quartile 1 to 4 based on SII. Four binary logistic regression models were constructed to progressively adjust for confounders and evaluate the association between SII and CAS, with further stratification by sex. Mediation analyses stratified by sex. Mediation analyses stratified by sex were performed using the Bootstrap method(5 000 resamplings), with white blood cell and monocyte counts as mediators. Sensitivity analyses were conducted to verify robustness.Results: A total of 19 788 participants were included, of whom 7 567(38.24%) had CAS. Compared with controls, individuals with CAS had significantly higher proportions of males, age, waist circumference, systolic and diastolic blood pressure, fasting glucose, and white blood cell count(all P<0.001), and significantly lower high-density lipoprotein cholesterol levels(P<0.001). Logistic regression revealed notable sex heterogeneity. After adjusting for age and sex(Model 2), higher SII(Quartile 4) was significantly associated with increased CAS risk [odds ratio(OR)=1.26, 95% confidence interval(CI) 1.14 to 1.39, P<0.01]. This association persisted after further adjustment for metabolic risk factors(Model 3; OR=1.18, 95% CI 1.07 to 1.31, P<0.01). However, after additional adjustment for inflammatory markers such as C-reactive protein, white blood cell, and monocyte counts(Model 4), the association was substantially attenuated and became non-significant in the overall population and in men(P>0.05). Notably, among women, SII remained significantly associated with CAS across all models in both Quartile 2(OR=1.19, 95% CI 1.02 to 1.39) and Quartile 4(OR=1.20, 95% CI 1.01 to 1.43) groups(all P<0.05). Mediation analysis showed that in the overall population, white blood cell count exerted a complete mediating effect(indirect effect β=0.03, 95% CI 0.01 to 0.05, P<0.01; accounting for 46.3% of the total effect), while monocyte count partially mediated the association(indirect effect β=0.01, 95% CI 0 to 0.02, P<0.01; accounting for 18.9% of the total effect). Among men, the mediating role of inflammatory cells was amplified, with white blood cell count serving as a complete mediator(indirect effect β=0.04, 95% CI 0.02 to 0.06, P<0.01; accounting for 74.3% of the total effect) and monocyte count as a significant partial mediator(indirect effect β =0.01, 95% CI 0 to 0.02, P<0.05; accounting for 24.2% of the total effect). Among women, the mediating effect of monocyte count(β=0, 95% CI 0 to 0, P>0.05), and white blood cell count(β =0.01, 95% CI 0 to 0.02, P>0.05) were not statistically significant. After adjusting for all confounding factors, the direct effect of SII on CAS remained statistically significant in all cases(all P<0.05). Sensitivity analyses confirmed the robustness of the findings.Conclusion: A significant sex-specific heterogeneity exists in the association between SII and CAS. High SII is an independent correlate of CAS in women, driven primarily by direct effects and not mediated by white blood cell or monocyte counts. In men, SII influences CAS predominantly through complete mediation by white blood cells and partial mediation by monocytes. These findings suggest the differentiated value of SII in CAS risk assessment across sexes and provide evidence to support sex-targeted screening and intervention strategies.更多还原