Tang Haoxian, Huang Jingtao, Lin Hanyuan, Zhang Xuan, Yang Qinglong, Luo Nan, Lin Mengyue, Tian Cuihong, Wu Shiwan, Hong Jianan, Wen Jiasheng, Jiang Liwen, Chen Pan, Chen Xiaojing, Tang Junshuang, Zhang Youti, Yi Kaihong, Tan Xuerui, Chen Yequn
Shantou University Medical College, Shantou, Guangdong, China.
Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou, Guangdong, China.
J Transl Med. 2025 Mar 22;23(1):359. doi: 10.1186/s12967-025-06375-9.
Understanding the evolving patterns of cardiovascular disease (CVD) burden attributable to ambient particulate matter pollution (APMP) is essential. Furthermore, research on the underlying mechanisms has mostly been limited to laboratory and animal models, with few large-scale population-based studies.
Using data from the Global Burden of Disease Study (GBD) 2021, we analyzed disability-adjusted life years and mortality for CVD attributable to APMP (measured as particulate matter [PM]) from 1990 to 2021. We examined shifts in burden between APMP and household air pollution (HAP), regional disparities by socio-demographic index (SDI), and predicted trends using a Bayesian age-period-cohort model. Additionally, we used UK Biobank (UKB) data (metabolomics: 230,000 + participants; proteomics: 50,000 +) to identify biomarkers mediating the association between PM exposure and CVD outcomes, and further analyzed their biological roles. Metabolic and proteomic signatures were constructed using regression and elastic net models, with predictive performance assessed via time-dependent receiver operating characteristic analysis. Life expectancy was evaluated using flexible parametric survival models. Subgroup analysis was conducted by age, sex, lifestyle, socioeconomic status, and genetic susceptibility.
In 2021, the global CVD absolute burden attributable to APMP was more than double that of 1990, with significant regional disparities. The burden shifted from HAP to APMP, with 15% of CVD cases globally attributed to APMP. The CVD burden attributable to APMP increased with age and is projected to rise through 2030. In the UKB, approximately 30 metabolites, including albumin, mediated the association between PM exposure and CVD outcomes, primarily involving lipid and fatty acids metabolism. Over 60 proteins, including growth differentiation factor-15 and trefoil factor 2, mediated the association with CVD outcomes, enriched in cytokine-receptor interaction and leukocyte migration pathways. Metabolic and proteomic signatures outperformed PM alone in predicting 1-, 5-, and 10-year CVD outcomes. Participants in the lowest decile of PM exposure, metabolic, and proteomic signatures had longer life expectancy than those in the highest decile.
The CVD burden attributable to APMP remains a critical public health concern. This study presents a novel approach for identifying and managing susceptible populations through metabolomic and proteomic perspectives.
了解由环境颗粒物污染（APMP）导致的心血管疾病（CVD）负担的演变模式至关重要。此外，对潜在机制的研究大多局限于实验室和动物模型，大规模的基于人群的研究较少。
利用全球疾病负担研究（GBD）2021的数据，我们分析了1990年至2021年因APMP（以颗粒物[PM]衡量）导致的CVD的伤残调整生命年和死亡率。我们研究了APMP和家庭空气污染（HAP）之间负担的变化、社会人口指数（SDI）导致的区域差异，并使用贝叶斯年龄-时期-队列模型预测趋势。此外，我们使用英国生物银行（UKB）的数据（代谢组学：230,000多名参与者；蛋白质组学：50,000多名）来识别介导PM暴露与CVD结局之间关联的生物标志物，并进一步分析它们的生物学作用。使用回归和弹性网络模型构建代谢和蛋白质组学特征，并通过时间依赖性受试者工作特征分析评估预测性能。使用灵活的参数生存模型评估预期寿命。按年龄、性别、生活方式、社会经济地位和遗传易感性进行亚组分析。
2021年，全球因APMP导致的CVD绝对负担比1990年增加了一倍多，存在显著的区域差异。负担从HAP转移到APMP，全球15%的CVD病例归因于APMP。因APMP导致的CVD负担随年龄增加，预计到2030年还会上升。在UKB中，约30种代谢物，包括白蛋白，介导了PM暴露与CVD结局之间的关联，主要涉及脂质和脂肪酸代谢。60多种蛋白质，包括生长分化因子-15和三叶因子2，介导了与CVD结局的关联，富集于细胞因子-受体相互作用和白细胞迁移途径。代谢和蛋白质组学特征在预测1年、5年和10年CVD结局方面比单独的PM表现更好。PM暴露、代谢和蛋白质组学特征处于最低十分位数的参与者的预期寿命比最高十分位数的参与者更长。
因APMP导致的CVD负担仍然是一个关键的公共卫生问题。本研究提出了一种通过代谢组学和蛋白质组学视角识别和管理易感人群的新方法。
