Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease.
Eur Heart J
; 40(34): 2883-2896, 2019 09 07.
Article
em En
| MEDLINE
| ID: mdl-31102408
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
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Doenças Cardiovasculares
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Doenças das Artérias Carótidas
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article