Large-scale plasma metabolic profiling identifies signatures and biomarkers associated with air pollution and arrhythmias: A prospective cohort study from UK Biobank

IF 6.6 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2026-10-15 DOI:10.1016/j.ecoenv.2026.120919

Hongguang Wu, Nan He, Peiyao Li, Juda Hu, Jing Chen, Xiaohong Li, Xiangming Hu, Yangning Zhang, Jin Bu, Ye Ma, Alwadi Yazan, Petros Koutrakis, Feiying He, Yanqiu Ou

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引用次数: 0

Abstract

Background

Air pollution is an established modifiable risk factor for cardiac arrhythmia, yet the metabolic mechanisms underlying this association remain poorly understood. This study aimed to elucidate how air pollutants promote arrhythmias through metabolic pathway perturbations.

Methods

We conducted a prospective analysis of 449,068 UK Biobank participants without baseline arrhythmia. Exposures to PM_2.5, PM₁₀, NO₂, and NO_x were assessed using land use regression models. Plasma metabolomic profiling including 170 metabolites via 1H-NMR was performed at baseline. Elastic net regression, Cox proportional hazards models, and mediation analysis were employed to identify pollutant-associated metabolic signatures, quantify their mediating effects, and characterize pathway enrichment across different kinds of arrhythmias.

Results

During a median follow-up of 16.31 years, a total of 47,381 arrhythmia cases were identified. All four pollutants were prospectively associated with increased arrhythmia risk (hazard ratios ranged from 1.015 to 1.257 per 10 μg/m³). The derived metabolomic signatures significantly mediated these associations between different air pollutants and arrhythmia (mediation proportions: PM_2.5-related, 11.19%; PM₁₀-related, 5.19%; NO₂-related, 7.44%; NO_x-related, 9.82%). Pathway enrichment analysis consistently identified lipid metabolism, ketone body metabolism, and amino acid metabolism as core affected pathways. Notably, compared to atrial fibrillation and supraventricular tachycardia, the ketone body metabolic pathway appeared to account for a larger proportion of the association with intraventricular block.

Conclusions

This study suggests that air pollution increases arrhythmia risk through distinct, subtype-specific metabolic perturbations, providing novel insights into the metabolic pathways linking environmental pollutants to different arrhythmia subtypes.

查看原文本刊更多论文

大规模血浆代谢分析识别与空气污染和心律失常相关的特征和生物标志物：来自英国生物银行的一项前瞻性队列研究。

背景：空气污染是心律失常的一个确定的可改变的危险因素，然而这种关联背后的代谢机制仍然知之甚少。本研究旨在阐明空气污染物如何通过代谢途径的扰动促进心律失常。方法：我们对449,068名无基线心律失常的英国生物银行参与者进行了前瞻性分析。利用土地利用回归模型评估PM2.5、PM10、NO2和NOx的暴露情况。在基线时通过1H-NMR进行血浆代谢组学分析，包括170种代谢物。采用弹性网回归、Cox比例风险模型和中介分析来识别污染物相关的代谢特征，量化其中介作用，并表征不同类型心律失常的途径富集。结果：在中位随访16.31年期间，共发现47,381例心律失常病例。所有四种污染物都与心律失常风险增加相关（风险比范围为1.015至1.257 / 10 μg/m3）。衍生的代谢组学特征显著介导了不同空气污染物与心律失常之间的关联（介导比例：pm2.5相关，11.19%；pm10相关，5.19%；no2相关，7.44%；nox相关，9.82%）。途径富集分析一致认为脂质代谢、酮体代谢和氨基酸代谢是核心影响途径。值得注意的是，与心房颤动和室上性心动过速相比，酮体代谢途径似乎在与室内传导阻滞的关联中占更大的比例。结论：本研究表明，空气污染通过不同的亚型特异性代谢扰动增加心律失常风险，为将环境污染物与不同心律失常亚型联系起来的代谢途径提供了新的见解。

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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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.