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Circulation. 2018 Feb 20;137(8):841-853. doi: 10.1161/CIRCULATIONAHA.117.029468.

Metabolic Predictors of Incident Coronary Heart Disease in Women.

Author information

1
Division of Preventive Medicine (N.P.P., F.G., J.E.M., N.R.C., C.M.A., K.M.R.) npaynter@partners.org.
2
Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst (R.B.).
3
Division of Preventive Medicine (N.P.P., F.G., J.E.M., N.R.C., C.M.A., K.M.R.).
4
Department of Epidemiology (D.D.W., J.E.M., N.R.C.).
5
Department of Nutrition (D.D.W., M.A.M.-G.), Harvard T.H. Chan School of Public Health, Boston, MA.
6
Fred Hutchinson Cancer Research Center, Seattle, WA (L.F.T.).
7
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA (S.G., A.A.D., K.B., K.A.P., J.S., C.B.C.).
8
Department of Preventive Medicine and Public Health, University of Navarra Medical School, Pamplona, Spain (M.A.M.-G.).
9
Department of Internal Medicine, Institut d'Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, University of Barcelona, Spain (R.E.).
10
Division of Women's Health (K.M.R.), Brigham and Women's Hospital, Boston, MA.

Abstract

BACKGROUND:

Although metabolomic profiling offers promise for the prediction of coronary heart disease (CHD), and metabolic risk factors are more strongly associated with CHD in women than men, limited data are available for women.

METHODS:

We applied a liquid chromatography-tandem mass spectrometry metabolomics platform to measure 371 metabolites in a discovery set of postmenopausal women (472 incident CHD cases, 472 controls) with validation in an independent set of postmenopausal women (312 incident CHD cases, 315 controls).

RESULTS:

Eight metabolites, primarily oxidized lipids, were significantly dysregulated in cases after the adjustment for matching and CHD risk factors in both the discovery and validation data sets. One oxidized phospholipid, C34:2 hydroxy-phosphatidylcholine, remained associated with CHD after further adjustment for other validated metabolites. Subjects with C34:2 hydroxy-phosphatidylcholine levels in the highest quartile had a 4.7-fold increase in CHD odds in comparison with the lowest quartile; C34:2 hydroxy-phosphatidylcholine also significantly improved the area under the curve (P<0.01) for CHD. The C34:2 hydroxy-phosphatidylcholine findings were replicated in a third replication data set of 980 men and women (230 cardiovascular events) with a stronger association observed in women.

CONCLUSIONS:

These data replicate known metabolite predictors, identify novel markers, and support the relationship between lipid oxidation and subsequent CHD.

KEYWORDS:

coronary disease; lipids; metabolomics; risk; women

PMID:
29459470
PMCID:
PMC5854187
[Available on 2019-02-20]
DOI:
10.1161/CIRCULATIONAHA.117.029468

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