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

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Title: Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease
Authors: Tzoulaki, I
Karaman, I
Dehghan, A
Ebbels, T
Holmes, E
Chambers, J
Kooner, J
Evangelou, E
Boulange, C
Kaluarachchi, M
Chadeau, M
Chekmeneva, E
Castagne, R
Loh, M
Lindon, J
Elliott, P
Item Type: Journal Article
Abstract: Aims: To characterise 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 (1H) nuclear magnetic resonance (NMR) spectroscopy among 3,867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3,569 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 NMR measured metabolites were associated with CAC and/or IMT, P =1.3x10-14 to 6.5x10-6 (discovery), P =4.2x10-14 to 4.4x10-2 (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.
Issue Date: 18-May-2019
Date of Acceptance: 15-Feb-2019
ISSN: 1522-9645
Publisher: Oxford University Press (OUP)
Journal / Book Title: European Heart Journal
Copyright Statement: This paper is embargoed until publication. Once published it will be available fully open access.
Sponsor/Funder: Commission of the European Communities
Imperial College Healthcare NHS Trust- BRC Funding
National Institutes of Health
National Institutes of Health
Health Data Research Uk
Funder's Grant Number: 305422
RDB03 79560
Health Data Research UK
Keywords: 1102 Cardiovascular Medicine And Haematology
Cardiovascular System & Hematology
Publication Status: Accepted
Embargo Date: publication subject to indefinite embargo
Appears in Collections:Division of Surgery
Faculty of Medicine
Epidemiology, Public Health and Primary Care

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