Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease
-
- Ioanna Tzoulaki
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Raphaële Castagné
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Claire L Boulangé
- Metabometrix Ltd , Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK
-
- Ibrahim Karaman
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Elena Chekmeneva
- Imperial College London Division of Computational and Systems Medicine, Department of Surgery and Cancer, , South Kensington Campus, London, UK
-
- Evangelos Evangelou
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Timothy M D Ebbels
- Imperial College London Division of Computational and Systems Medicine, Department of Surgery and Cancer, , South Kensington Campus, London, UK
-
- Manuja R Kaluarachchi
- Metabometrix Ltd , Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK
-
- Marc Chadeau-Hyam
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- David Mosen
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Abbas Dehghan
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Alireza Moayyeri
- Farr Institute of Health Informatics Research, University College London Institute of Health Informatics , 222 Euston Road, London, UK
-
- Diana L Santos Ferreira
- University of Bristol MRC Integrative Epidemiology Unit, School of Social and Community Medicine, , Oakfield House, Oakfiled Grove, Bristol, UK
-
- Xiuqing Guo
- Institute for Translational Genomics and Population Sciences Department of Pediatrics, , Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA
-
- Jerome I Rotter
- Institute for Translational Genomics and Population Sciences Department of Pediatrics, , Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA
-
- Kent D Taylor
- Institute for Translational Genomics and Population Sciences Department of Pediatrics, , Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA
-
- Maryam Kavousi
- Erasmus University Medical Center, University Medical Center Rotterdam Department of Epidemiology, , CA Rotterdam, the Netherlands
-
- Paul S de Vries
- Erasmus University Medical Center, University Medical Center Rotterdam Department of Epidemiology, , CA Rotterdam, the Netherlands
-
- Benjamin Lehne
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Marie Loh
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Albert Hofman
- Erasmus University Medical Center, University Medical Center Rotterdam Department of Epidemiology, , CA Rotterdam, the Netherlands
-
- Jeremy K Nicholson
- Metabometrix Ltd , Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK
-
- John Chambers
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
-
- Christian Gieger
- German Research Centre for Environmental Health , Helmholtz Zentrum München, Ingolstädter Landstraße 1, D Neuherberg, Germany
-
- Elaine Holmes
- Metabometrix Ltd , Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK
-
- Russell Tracy
- M.D. College of Medicine University of Vermont , The Robert Larner, Given Medical Bldg, E-126, 89 Beaumont Ave, Burlington, VT, USA
-
- Jaspal Kooner
- Department of Epidemiology, Harvard T.H. Chan School of Public Health , 677 Huntington Avenue, Boston, MA, USA
-
- Philip Greenland
- Northwestern University Department of Preventive Medicine, , Feinberg School of Medicine, 680 North Lake Shore Drive, Suite, 1400, Chicago, IL, USA
-
- Oscar H Franco
- Institute for Translational Genomics and Population Sciences Department of Medicine, , Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA
-
- David Herrington
- Wake Forest University School of Medicine, Medical Center Boulevard Section on Cardiovascular Medicine, Department of Internal Medicine, , Winston-Salem, NC, USA
-
- John C Lindon
- Metabometrix Ltd , Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK
-
- Paul Elliott
- Imperial College London Department of Epidemiology and Biostatistics, School of Public Health, , Norfolk Place, London, UK
Description
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Aims</jats:title> <jats:p>To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and results</jats:title> <jats:p>We used untargeted one-dimensional (1D) serum metabolic profiling by proton nuclear magnetic resonance spectroscopy (1H NMR) among 3867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3569 participants from the Rotterdam and LOLIPOP studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 1H NMR measured metabolites were associated with CAC and/or IMT, P = 1.3 × 10−14 to 1.0 × 10−6 (discovery) and P = 5.6 × 10−10 to 1.1 × 10−2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched chain, and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine, and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide, and lactate as well as apolipoprotein B (P < 0.05).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis.</jats:p> <jats:p /> </jats:sec>
Journal
-
- European Heart Journal
-
European Heart Journal 40 (34), 2883-2896, 2019-05-18
Oxford University Press (OUP)
- Tweet
Details 詳細情報について
-
- CRID
- 1360017290218470528
-
- ISSN
- 15229645
- 0195668X
-
- Data Source
-
- Crossref