{
  "abstract": "Background Ambient air pollution is associated with heart failure (HF), but underlying biological mechanisms remain unclear. We aimed to elucidate metabolic pathways linking air pollution exposure with HF.Methods This prospective cohort study analysed 229 812 UK Biobank participants with nuclear magnetic resonance metabolomics data. Air pollution score was constructed by fine particulate matter, coarse particulate matter, nitrogen dioxide and nitrogen oxides. Air pollution-associated metabolic signatures were identified using elastic net regression among 251 circulating metabolites. Cox regression evaluated associations between metabolic signatures and incident HF risk. Mediation analysis quantified metabolic signatures’ role in air pollution–HF relationships.Results During median 13.1-year follow-up, 8986 participants (3.9%) developed HF. We identified 53 metabolic metabolites reflecting air pollution exposure, comprising lipoprotein metabolism markers (22.6%), fatty acids (17.0%) and amino acids (13.2%), which were used to construct the air pollution-related metabolic signatures score. After adjustment for confounding factors, each SD increase in the metabolic signatures was associated with 8% elevated HF risk (HR 1.08, 95% CI 1.06 to 1.11). Participants in the highest quantile showed a 24% increased HF risk compared with those in the lowest quantile (HR 1.24, 95% CI 1.16 to 1.3). The metabolic signatures mediated 13.08% (95% CI 12.15% to 15.71%) of air pollution–HF associations, with lipoprotein metabolism and fatty acid signatures as primary mediators.Conclusions Air pollution was associated with increased HF risk, with metabolic perturbations appearing to play a mediating role. These metabolic signatures provide insights into potential mechanisms linking air pollution to cardiovascular outcomes.",
  "authors": [
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Chaojun Yang"
    },
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Zhixing Fan"
    },
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Jing Zhang"
    },
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Hui Wu"
    },
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Zeng Ping"
    },
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Huibo Wang"
    },
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Ying Yang"
    },
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Qi Li"
    },
    {
      "affiliations": [
        "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China",
        "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, Hubei, China",
        "Interdisciplinary Institute for Advanced Medicine and Engineering, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China"
      ],
      "name": "Jian Yang"
    }
  ],
  "title": "Air pollution-related metabolic profiles and subsequent heart failure risk",
  "uid": "6fb50fd8-cc5e-5cb3-b336-e0996548245e"
}