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@article{Tzoulaki:2019:eurheartj/ehz235,
author = {Tzoulaki, I and Castagné, R and Boulangé, CL and Karaman, I and Chekmeneva, E and Evangelou, E and Ebbels, TMD and Kaluarachchi, MR and Chadeau-Hyam, M and Mosen, D and Dehghan, A and Moayyeri, A and Ferreira, DLS and Guo, X and Rotter, JI and Taylor, KD and Kavousi, M and De, Vries PS and Lehne, B and Loh, M and Hofman, A and Nicholson, JK and Chambers, J and Gieger, C and Holmes, E and Tracy, R and Kooner, J and Greenland, P and Franco, OH and Herrington, D and Lindon, JC and Elliott, P},
doi = {eurheartj/ehz235},
journal = {European Heart Journal},
pages = {2883--2896},
title = {Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease},
url = {http://dx.doi.org/10.1093/eurheartj/ehz235},
volume = {40},
year = {2019}
}

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TY  - JOUR
AB  - 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 atherosclero
AU  - Tzoulaki,I
AU  - Castagné,R
AU  - Boulangé,CL
AU  - Karaman,I
AU  - Chekmeneva,E
AU  - Evangelou,E
AU  - Ebbels,TMD
AU  - Kaluarachchi,MR
AU  - Chadeau-Hyam,M
AU  - Mosen,D
AU  - Dehghan,A
AU  - Moayyeri,A
AU  - Ferreira,DLS
AU  - Guo,X
AU  - Rotter,JI
AU  - Taylor,KD
AU  - Kavousi,M
AU  - De,Vries PS
AU  - Lehne,B
AU  - Loh,M
AU  - Hofman,A
AU  - Nicholson,JK
AU  - Chambers,J
AU  - Gieger,C
AU  - Holmes,E
AU  - Tracy,R
AU  - Kooner,J
AU  - Greenland,P
AU  - Franco,OH
AU  - Herrington,D
AU  - Lindon,JC
AU  - Elliott,P
DO  - eurheartj/ehz235
EP  - 2896
PY  - 2019///
SN  - 1522-9645
SP  - 2883
TI  - Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease
T2  - European Heart Journal
UR  - http://dx.doi.org/10.1093/eurheartj/ehz235
UR  - http://hdl.handle.net/10044/1/68576
VL  - 40
ER  -

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