Open AccessPlasma metabolites mediate the effect of HbA1c on incident cardiovascular disease
Author(s) -
Dong Xuesi,
Zhou Wei,
Li Hu,
Fan Yuanming,
Yin Xiaojian,
Li Yong,
Chen Feng,
Ma Gaoxiang
Publication year - 2019
Publication title -
clinical cardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.263
H-Index - 72
eISSN - 1932-8737
pISSN - 0160-9289
DOI - 10.1002/clc.23243
Subject(s) - medicine , metabolism , endocrinology , metabolite , pharmacology
Background We aim to discover whether HbA1c affects incident cardiovascular disease (CVD) through regulating endogenous metabolites. Methods and Results Totally, 2019 plasma samples were analyzed by liquid chromatography‐quadrupole time‐of‐flight mass spectrometry. Logistic regression and linear regression were used to screen metabolites which were associated with both CVD and HbA1c. The VanderWeele's mediation approach was performed to assess the direct effect and indirect effect (IE) in the counterfactual model. Forty‐eight metabolites showed an association with both HbA1c and CVD risk. Forty‐four of the 48 metabolites worked as mediators mediated in HbA1c's effect on CVD (odds ratio [OR] IE from 0.997 to 6.098, false discovery rate q < 0.05, mediated proportion from 0.4% to 85.4%). Pathway enrichment analysis indicated that different metabolic pathway showed significant IE (butanoate metabolism OR IE = 1.058, mediated proportion = 16.0%; alanine, aspartate and glutamate metabolism OR IE = 1.082, mediated proportion = 21.8%; TCA (citric acid) cycle metabolism OR IE = 1.048, mediated proportion = 13.8%; phenylalanine metabolism OR IE = 1.067, mediated proportion = 18.4%; glycerophospholipid metabolism OR IE = 3.007, mediated proportion = 82.2%; all the P < .01). Conclusions Our findings suggest that metabolites mediate the effect of HbA1c on incident CVD and provide a new study sight into pathogenesis of CVD.