Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease.

Adult Aged Cardiovascular Diseases / blood Carotid Artery Diseases / blood Coronary Artery Disease / blood Female Humans Male Middle Aged Prospective Studies Proton Magnetic Resonance Spectroscopy
Atherosclerosis Coronary artery calcium Epidemiological studies Intima-media thickness Metabolic phenotyping Metabolomics

Journal

European heart journal
ISSN: 1522-9645
Titre abrégé: Eur Heart J
Pays: England
ID NLM: 8006263

Informations de publication

Date de publication:
07 09 2019
Historique:
received: 22 08 2018
revised: 21 11 2018
accepted: 13 05 2019
pubmed: 19 5 2019
medline: 18 11 2020
entrez: 19 5 2019
Statut: ppublish

Résumé

To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). 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). 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.

Identifiants

DOI: 10.1093/eurheartj/ehz235 PMID: 31102408 PMC: PMC7963131
pubmed: 31102408
pii: 5490734
doi: 10.1093/eurheartj/ehz235
pmc: PMC7963131
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2883-2896

Subventions

Organisme : NHLBI NIH HHS
ID : HHSN268201500003C
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95163
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001079
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133932
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95169
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95159
Pays : United States
Organisme : Medical Research Council
ID : MR/L01632X/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : N01HC95167
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000040
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95166
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : Department of Health
ID : HPRU-2012-10141
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : N01HC95160
Pays : United States
Organisme : NIH HHS
ID : HHSN263201500003I
Pays : United States
Organisme : Medical Research Council
ID : MR/L01341X/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : N01HC95164
Pays : United States
Organisme : NHLBI NIH HHS
ID : N02HL64278
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95162
Pays : United States
Organisme : NHLBI NIH HHS
ID : N02 HL64278
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95168
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01 HC095159
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95165
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95161
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001420
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500003I
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL111362
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

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Auteurs

Ioanna Tzoulaki (I)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, UK.
Department of Hygiene and Epidemiology, University of Ioannina Medical School, University Campus Road 455 00, Ioannina, Greece.
Dementia Research Institute, Imperial College London, Norfolk Place, London, UK.

Raphaële Castagné (R)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
LEASP, UMR 1027, Inserm-Université Toulousse III Paul Sabatier, Toulousse, France.

Claire L Boulangé (CL)

Metabometrix Ltd, Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK.
Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, South Kensington Campus, London, UK.

Ibrahim Karaman (I)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, UK.
Dementia Research Institute, Imperial College London, Norfolk Place, London, UK.

Elena Chekmeneva (E)

Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, South Kensington Campus, London, UK.

Evangelos Evangelou (E)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, UK.
Department of Hygiene and Epidemiology, University of Ioannina Medical School, University Campus Road 455 00, Ioannina, Greece.

Timothy M D Ebbels (TMD)

Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, South Kensington Campus, London, UK.

Manuja R Kaluarachchi (MR)

Metabometrix Ltd, Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK.
Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, South Kensington Campus, London, UK.

Marc Chadeau-Hyam (M)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, UK.

David Mosen (D)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, UK.

Abbas Dehghan (A)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, UK.
Dementia Research Institute, Imperial College London, Norfolk Place, London, UK.

Alireza Moayyeri (A)

Farr Institute of Health Informatics Research, University College London Institute of Health Informatics, 222 Euston Road, London, UK.

Diana L Santos Ferreira (DLS)

MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfiled Grove, Bristol, UK.

Xiuqing Guo (X)

Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA.
Department of Medicine, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA.

Jerome I Rotter (JI)

Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA.
Department of Medicine, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA.

Kent D Taylor (KD)

Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA.
Department of Medicine, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA.

Maryam Kavousi (M)

Department of Epidemiology, Erasmus University Medical Center, University Medical Center Rotterdam, CA Rotterdam, the Netherlands.

Paul S de Vries (PS)

Department of Epidemiology, Erasmus University Medical Center, University Medical Center Rotterdam, CA Rotterdam, the Netherlands.
Department of Epidemiology, Human Genetics, and Environmental Sciences, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, 1200 Pressler Street, Houston, TX, USA.

Benjamin Lehne (B)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.

Marie Loh (M)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.

Albert Hofman (A)

Department of Epidemiology, Erasmus University Medical Center, University Medical Center Rotterdam, CA Rotterdam, the Netherlands.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA.

Jeremy K Nicholson (JK)

Metabometrix Ltd, Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK.
Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, South Kensington Campus, London, UK.

John Chambers (J)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
London North West Healthcare NHS Trust, Northwick Park Hospital, Watford Rd, Harrow, UK.

Christian Gieger (C)

German Research Centre for Environmental Health, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D Neuherberg, Germany.

Elaine Holmes (E)

Metabometrix Ltd, Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK.
Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, South Kensington Campus, London, UK.

Russell Tracy (R)

M.D. College of Medicine University of Vermont, The Robert Larner, Given Medical Bldg, E-126, 89 Beaumont Ave, Burlington, VT, USA.

Jaspal Kooner (J)

Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA.
National Heart & Lung Institute, Faculty of Medicine, Imperial College London, Guy Scadding Building, Dovehouse St, Chelsea, London, UK.

Philip Greenland (P)

Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, 680 North Lake Shore Drive, Suite, 1400, Chicago, IL, USA.

Oscar H Franco (OH)

Department of Medicine, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, USA.
Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, Bern, Switzerland.

David Herrington (D)

Section on Cardiovascular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA.

John C Lindon (JC)

Metabometrix Ltd, Imperial Incubator, Bessemer Building, Prince Consort Road, London, UK.
Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, South Kensington Campus, London, UK.

Paul Elliott (P)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, UK.
Dementia Research Institute, Imperial College London, Norfolk Place, London, UK.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Serum metabolic signatures of coronary and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Serum metabolic signatures of coronary and...
questionsmedicales.fr › Maladies cardiovasculaires › Serum metabolic signatures of coronary and...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Angiopathies intracrâniennes › Artériopathies carotidiennes › Serum metabolic signatures of coronary and...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Ischémie myocardique › Maladie coronarienne › Maladie des artères coronaires › Serum metabolic signatures of coronary and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Serum metabolic signatures of coronary and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Serum metabolic signatures of coronary and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Serum metabolic signatures of coronary and...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Analyse spectrale › Spectroscopie par résonance magnétique › Spectroscopie par résonance magnétique du proton › Serum metabolic signatures of coronary and...