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

Abstract Aims To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). Methods and results We used untargeted one-dimensional (1D) serum metabolic profiling by proton...

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Veröffentlicht in:European heart journal Jg. 40; H. 34; S. 2883 - 2896
Hauptverfasser: Tzoulaki, Ioanna, Castagné, Raphaële, Boulangé, Claire L, Karaman, Ibrahim, Chekmeneva, Elena, Evangelou, Evangelos, Ebbels, Timothy M D, Kaluarachchi, Manuja R, Chadeau-Hyam, Marc, Mosen, David, Dehghan, Abbas, Moayyeri, Alireza, Ferreira, Diana L Santos, Guo, Xiuqing, Rotter, Jerome I, Taylor, Kent D, Kavousi, Maryam, de Vries, Paul S, Lehne, Benjamin, Loh, Marie, Hofman, Albert, Nicholson, Jeremy K, Chambers, John, Gieger, Christian, Holmes, Elaine, Tracy, Russell, Kooner, Jaspal, Greenland, Philip, Franco, Oscar H, Herrington, David, Lindon, John C, Elliott, Paul
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Oxford University Press 07.09.2019
Schlagworte:
Adult
Aged
Cardiovascular Diseases - blood
Cardiovascular Diseases - etiology
Carotid Artery Diseases - blood
Carotid Artery Diseases - complications
Carotid Artery Diseases - metabolism
Coronary Artery Disease - blood
Coronary Artery Disease - complications
Coronary Artery Disease - metabolism
Female
Humans
Male
Middle Aged
Prospective Studies
Proton Magnetic Resonance Spectroscopy
Intima-media thickness
Metabolomics
Epidemiological studies
Metabolic phenotyping
Coronary artery calcium
Atherosclerosis
ISSN:0195-668X, 1522-9645, 1522-9645
Online-Zugang:Volltext
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Zusammenfassung:Abstract Aims To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). Methods and results 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). Conclusion 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.
Bibliographie:ObjectType-Article-1
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content type line 23
ISSN:0195-668X
1522-9645
1522-9645
DOI:10.1093/eurheartj/ehz235