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.
journal_name
Circulationjournal_title
Circulationauthors
Paynter NP,Balasubramanian R,Giulianini F,Wang DD,Tinker LF,Gopal S,Deik AA,Bullock K,Pierce KA,Scott J,Martínez-González MA,Estruch R,Manson JE,Cook NR,Albert CM,Clish CB,Rexrode KMdoi
10.1161/CIRCULATIONAHA.117.029468subject
Has Abstractpub_date
2018-02-20 00:00:00pages
841-853issue
8eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.117.029468journal_volume
137pub_type
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