| Title: | Neutrophil-mediated effects of S100A12 on major adverse cardiovascular events: Insights from the UK biobank |
| Journal: | American Journal of Preventive Cardiology |
| Published: | 30 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40978300/ |
| DOI: | https://doi.org/10.1016/j.ajpc.2025.101278 |
Publication 19618
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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.</p>
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.</p>
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.</p>
Conclusion: Elevated S100A12 levels are independently associated with increased MACEs risk, with neutrophil count serving as a significant mediator.</p>
5 Authors
- Qingqing Zhang
- Xiangwei Ding
- Yanling Xu
- Yongping Lin
- Yucheng Wu
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