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J Am Heart Assoc. 2017 Sep 28;6(10). pii: e005705. doi: 10.1161/JAHA.117.005705.

Comprehensive Metabolomic Profiling and Incident Cardiovascular Disease: A Systematic Review.

Author information

1
Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
2
IDISNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain.
3
CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
4
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
5
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
6
The Broad Institute of MIT and Harvard, Cambridge, MA.
7
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
8
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
9
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA mamartinez@unav.es.
10
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Abstract

BACKGROUND:

Metabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease (CVD).

METHODS AND RESULTS:

We searched MEDLINE and EMBASE from inception to January 2016. Studies were eligible if they pertained to adult humans; followed an agnostic and/or comprehensive approach; used serum or plasma (not urine or other biospecimens); conducted metabolite profiling at baseline in the context of examining prospective disease; and included myocardial infarction, stroke, and/or CVD death in the CVD outcome definition. We identified 12 original articles (9 cohort and 3 nested case-control studies); participant numbers ranged from 67 to 7256. Mass spectrometry was the predominant analytical method. The number and chemical diversity of metabolites were very heterogeneous, ranging from 31 to >10 000 features. Four studies used untargeted profiling. Different types of metabolites were associated with CVD risk: acylcarnitines, dicarboxylacylcarnitines, and several amino acids and lipid classes. Only tiny improvements in CVD prediction beyond traditional risk factors were observed using these metabolites (C index improvement ranged from 0.006 to 0.05).

CONCLUSIONS:

There are a limited number of longitudinal studies assessing associations between comprehensive metabolomic profiles and CVD risk. Quantitatively synthesizing the literature is challenging because of the widely varying analytical tools and the diversity of methodological and statistical approaches. Although some results are promising, more research is needed, notably standardization of metabolomic techniques and statistical approaches. Replication and combinations of novel and holistic methodological approaches would move the field toward the realization of its promise.

KEYWORDS:

epidemiology; metabolomics; myocardial infarction; stroke

PMID:
28963102
PMCID:
PMC5721826
DOI:
10.1161/JAHA.117.005705
[Indexed for MEDLINE]
Free PMC Article

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