TY - JOUR
T1 - Urinary levels of trimethylamine-N-oxide and incident coronary heart disease
T2 - A prospective investigation among urban Chinese adults
AU - Yu, Danxia
AU - Shu, Xiao Ou
AU - Rivera, Emilio S.
AU - Zhang, Xianglan
AU - Cai, Qiuyin
AU - Calcutt, Marion W.
AU - Xiang, Yong Bing
AU - Li, Honglan
AU - Gao, Yu Tang
AU - Wang, Thomas J.
AU - Zheng, Wei
N1 - Funding Information:
The parent cohort studies were supported by grants from the National Institutes of Health UM1 CA182910 to Zheng and UM1 CA173640 to Shu. Yu was supported by Vanderbilt University Medical Center Faculty Research Scholars Program. The urine sample preparation was performed at the Survey and Biospecimen Shared Resource (Cai), which is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA068485). The bioanalytical methods development (Rivera and Calcutt) was supported in part by a Vanderbilt University Trans-Institutional Program Award to Dr Kevin L. Schey. The funding agencies had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the article; or decision to submit the article for publication. The contents of this article are solely responsibility of the authors and do not represent the official views of the Tennessee Department of Health.
Publisher Copyright:
© 2019 The Authors.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Background-—Trimethylamine-N-oxide (TMAO), a diet-derived, gut microbial–host cometabolite, has been associated with adverse cardiovascular outcomes in patient populations; however, evidence is lacking from prospective studies conducted in general populations and non-Western populations. Methods and Results-—We evaluated urinary levels of TMAO and its precursor metabolites (ie, choline, betaine, and carnitine) in relation to risk of coronary heart disease (CHD) among Chinese adults in a nested case–control study, including 275 participants with incident CHD and 275 individually matched controls. We found that urinary TMAO, but not its precursors, was associated with risk of CHD. The odds ratio for the highest versus lowest quartiles of TMAO was 1.91 (95% CI, 1.08–3.35; P trend =0.008) after adjusting for CHD risk factors including obesity, diet, lifestyle, and metabolic diseases and 1.75 (95% CI, 0.96–3.18; P trend =0.03) after further adjusting for potential confounders or mediators including central obesity, dyslipidemia, inflammation, and intake of seafood and deep-fried meat or fish, which were associated with TMAO level in this study. The odds ratio per standard deviation increase in log-TMAO was 1.30 (95% CI, 1.03–1.63) in the fully adjusted model. A history of diabetes mellitus modified the TMAO– CHD association. A high TMAO level (greater than or equal to versus lower than the median) was associated with odds ratios of 6.21 (95% CI, 1.64–23.6) and 1.56 (95% CI, 1.00–2.43), respectively, among diabetic and nondiabetic participants (P interaction =0.02). Diabetes mellitus status also modified the associations of choline, betaine, and carnitine with risk of CHD; significant positive associations were found among diabetic participants, but null associations were noted among total and nondiabetic participants. Conclusions-—Our study suggests that TMAO may accelerate the development of CHD, highlighting the importance of diet–gut microbiota–host interplay in cardiometabolic health.
AB - Background-—Trimethylamine-N-oxide (TMAO), a diet-derived, gut microbial–host cometabolite, has been associated with adverse cardiovascular outcomes in patient populations; however, evidence is lacking from prospective studies conducted in general populations and non-Western populations. Methods and Results-—We evaluated urinary levels of TMAO and its precursor metabolites (ie, choline, betaine, and carnitine) in relation to risk of coronary heart disease (CHD) among Chinese adults in a nested case–control study, including 275 participants with incident CHD and 275 individually matched controls. We found that urinary TMAO, but not its precursors, was associated with risk of CHD. The odds ratio for the highest versus lowest quartiles of TMAO was 1.91 (95% CI, 1.08–3.35; P trend =0.008) after adjusting for CHD risk factors including obesity, diet, lifestyle, and metabolic diseases and 1.75 (95% CI, 0.96–3.18; P trend =0.03) after further adjusting for potential confounders or mediators including central obesity, dyslipidemia, inflammation, and intake of seafood and deep-fried meat or fish, which were associated with TMAO level in this study. The odds ratio per standard deviation increase in log-TMAO was 1.30 (95% CI, 1.03–1.63) in the fully adjusted model. A history of diabetes mellitus modified the TMAO– CHD association. A high TMAO level (greater than or equal to versus lower than the median) was associated with odds ratios of 6.21 (95% CI, 1.64–23.6) and 1.56 (95% CI, 1.00–2.43), respectively, among diabetic and nondiabetic participants (P interaction =0.02). Diabetes mellitus status also modified the associations of choline, betaine, and carnitine with risk of CHD; significant positive associations were found among diabetic participants, but null associations were noted among total and nondiabetic participants. Conclusions-—Our study suggests that TMAO may accelerate the development of CHD, highlighting the importance of diet–gut microbiota–host interplay in cardiometabolic health.
KW - Cardiovascular disease risk factors
KW - Chinese
KW - Gut microbiota
KW - Metabolomics
KW - Nested case-control study
KW - Nutrition
KW - Prospective cohort study
KW - Trimethylamine-N-oxide
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U2 - 10.1161/JAHA.118.010606
DO - 10.1161/JAHA.118.010606
M3 - Article
C2 - 30606084
AN - SCOPUS:85059497493
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 1
M1 - e010606
ER -