Neutrophil-mediated effects of S100A12 on major adverse cardiovascular events: Insights from the UK biobank

IF 5.9 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

American journal of preventive cardiology Pub Date : 2025-09-01 DOI:10.1016/j.ajpc.2025.101278

Qingqing Zhang , Xiangwei Ding , Yanling Xu , Yongping Lin , Yucheng Wu

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引用次数: 0

Abstract

Background

S100A12, a pro-inflammatory protein primarily secreted by neutrophils, has been implicated in vascular inflammation and atherosclerosis. However, its role in major adverse cardiovascular events (MACE) remains unclear. This study aimed to investigate the association between plasma S100A12 levels and MACE risk, and to assess the potential mediating role of neutrophil count in this relationship.

Methods

We conducted a prospective cohort study using data from the UK Biobank (N = 47,106). Participants with prior MACE or missing S100A12 or neutrophil count data were excluded. MACE was defined as a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Cox proportional hazards models were used to assess the association between S100A12 and MACE risk, adjusting for demographics, lifestyle factors, metabolic parameters, and genetic predisposition. Mediation analysis was conducted to evaluate the indirect effect of neutrophil count on this association.

Results

During a median follow-up of 15.3 years, 2,250 (4.8 %) participants experienced MACE, with a total follow-up time of 695,581.4 patient-years. Higher S100A12 levels were significantly associated with an increased risk of MACE (HR: 1.115, 95 % CI: 1.050–1.183, P < 0.0001), with a dose‒response relationship observed across tertiles (P for trend < 0.0001). The association remained robust after adjusting for multiple covariates and in sensitivity analyses. Subgroup analyses showed consistent results across age, sex, and metabolic risk factors. Mediation analysis revealed that neutrophil count mediated 44.10 % of the association between S100A12 and MACE (P < 0.0001), supporting a neutrophil-driven inflammatory mechanism.

Conclusion

Elevated S100A12 levels are independently associated with increased MACEs risk, with neutrophil count serving as a significant mediator.

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中性粒细胞介导的S100A12对主要不良心血管事件的影响：来自英国生物银行的见解

ds100a12是一种主要由中性粒细胞分泌的促炎蛋白，与血管炎症和动脉粥样硬化有关。然而，其在主要不良心血管事件（MACE）中的作用尚不清楚。本研究旨在探讨血浆S100A12水平与MACE风险之间的关系，并评估中性粒细胞计数在这一关系中的潜在中介作用。方法采用来自英国生物银行（UK Biobank）的数据进行前瞻性队列研究（N = 47,106）。既往有MACE或缺少S100A12或中性粒细胞计数数据的参与者被排除在外。MACE被定义为非致死性心肌梗死、非致死性卒中和心血管死亡的复合。使用Cox比例风险模型评估S100A12与MACE风险之间的关系，调整人口统计学、生活方式因素、代谢参数和遗传易感性。进行中介分析以评估中性粒细胞计数对这种关联的间接影响。结果在15.3年的中位随访期间，2250名（4.8%）参与者经历了MACE，总随访时间为695,581.4患者年。较高的S100A12水平与MACE风险增加显着相关（HR: 1.115, 95% CI: 1.050-1.183, P < 0.0001），并且在各组间观察到剂量-反应关系（P为趋势<； 0.0001）。在调整了多个协变量和敏感性分析后，这种关联仍然是稳健的。亚组分析显示，不同年龄、性别和代谢危险因素的结果一致。中介分析显示，中性粒细胞计数介导了S100A12与MACE之间44.10%的关联（P < 0.0001），支持中性粒细胞驱动的炎症机制。结论S100A12水平升高与mace风险增加独立相关，中性粒细胞计数是一个重要的中介。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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