Abstract
Introduction:
In the US, African Americans (AA) have higher cardiovascular disease (CVD) morbidity and mortality than whites. Recent evidence suggests that the CVD development may be related to circulating metabolite alterations, which might contribute to racial disparities in CVD risk.
Hypothesis:
We tested the hypothesis that metabolomic profile of AAs differ from that of whites.
Methods:
Metabolomic profiling in plasma samples of 2,128 women from the Women’s Health Initiative (WHI) was performed using liquid chromatography-tandem mass spectrometry, and 422 known metabolites were measured. The discovery set included 834 women (138 AAs) from the WHI Observational Study. The replication set included 1,294 women (156 AAs) from the WHI Hormone Therapy Trials. Linear regression models were applied to individually estimate the association of race (AA vs. white) with each metabolite, adjusting for age, body mass index, education, income, healthy eating index-2005, physical activity, smoking, alcohol intake, hypertension, diabetes, depression, and medications. Metabolites with a false discovery rate-adjusted
P
<0.05 in the discovery set were then replicated in the replication set with a Bonferroni corrected
P
<0.05 indicating statistical significance.
Results:
We identified 178 metabolites that significantly differed between AAs and whites in both discovery and replication sets, the majority of which were lipids, followed by amino acids and their derivatives (Panel A). For the 178 metabolites, the mean levels of 126 metabolites differed between AAs and Whites by at least 0.5 standard deviation units; 9 of these metabolites (1 triacylglycerol, 3 phosphatidylcholines, 2 phosphatidylethanolamine plasmalogens, and 3 cholesteryl esters) had mean differences exceeding 1-standard deviation unit (Panel B).
Conclusions:
Metabolomic profiles significantly differed between AAs and whites, especially lipid metabolites, and these race-associated alterations may contribute to racial disparities in cardiovascular risk.