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Association between myeloperoxidase and the risks of ischemic stroke, heart failure, and atrial fibrillation: A Mendelian randomization study

  • Author Footnotes
    1 These authors contributed equally to this work.
    Yinan Wang
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Yiming Jia
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Qingyun Xu
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Ruirui Wang
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Lulu Sun
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Daoxia Guo
    Affiliations
    School of Nursing, Suzhou Medical College of Soochow University, Suzhou, China
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  • Mengyao Shi
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Pinni Yang
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Yu Wang
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Fanghua Liu
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Yonghong Zhang
    Correspondence
    Corresponding author. Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province 215123, China.
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
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  • Zhengbao Zhu
    Correspondence
    Corresponding author. Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province 215123, China.
    Affiliations
    Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:October 14, 2022DOI:https://doi.org/10.1016/j.numecd.2022.09.027

      Highlights

      • We investigated the association of MPO with the risks of ischemic stroke, HF, and AF from a genetic standpoint.
      • This is the first MR study assessing the potential causal role of MPO in the development of cardiovascular diseases.
      • MPO levels were causally associated with increased risks of ischemic stroke, CES, HF, and AF.
      • Decreasing MPO levels or inhibiting its activity might be a promising preventive target for cardiovascular diseases.

      Abstract

      Background and aims

      The causality between myeloperoxidase (MPO) and cardiovascular disease still remains unclear. We performed a two-sample Mendelian randomization (MR) study to estimate the potential causal effect of MPO on the risks of ischemic stroke, ischemic stroke subtypes, heart failure (HF), and atrial fibrillation (AF).

      Methods and results

      Seventeen independent single-nucleotide polymorphisms associated with MPO levels were identified as instrumental variables from a European-descent genome-wide association study. Summary-level data on ischemic stroke originated from the Multiancestry Genome-wide Association Study of Stroke Consortium with 440 328 European individuals. We used the inverse-variance weighted method to assess the potential causality of plasma MPO with ischemic stroke and its subtypes in the main analysis. Genetically determined higher plasma MPO concentration was significantly associated with increased risks of ischemic stroke (odds ratio [OR] per standard deviation [SD] increase, 1.05; 95% confidence interval [CI], 1.02–1.09; P = 0.002) and cardioembolic stroke (CES) (OR per SD increase, 1.10; 95% CI, 1.03–1.18; P = 0.005), but was not associated with risks of large artery stroke or small vessel stroke. In the secondary analysis, MPO was associated with a high risk of HF (OR per SD increase, 1.05; 95% CI, 1.02–1.07; P = 0.001) and AF (OR per SD increase, 1.04; 95% CI, 1.01–1.07; P = 0.004). MR-Egger regression showed no directional pleiotropy for all associations, and the sensitivity analyses further confirmed these findings.

      Conclusion

      High plasma MPO levels were potentially associated with increased risks of ischemic stroke, CES, HF, and AF, suggesting that MPO plays an important role in the development of cardiovascular disease.

      Keywords

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