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J Cell Mol Med. 2018 Jan;22(1):185-194. doi: 10.1111/jcmm.13307. Epub 2017 Aug 7.

Circulating trimethylamine N-oxide and the risk of cardiovascular diseases: a systematic review and meta-analysis of 11 prospective cohort studies.

Qi J1,2,3,4, You T1,2,3,4, Li J2, Pan T1,2,3,4, Xiang L5, Han Y2,3,4, Zhu L1,3,4.

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Cyrus Tang Medical Institute, Soochow University, Suzhou, Jiangsu, China.
Jiangsu Institute of Haematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Jiangsu Collaborative Innovation Centre of Haematology, Suzhou, China.
Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China.
Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.


Circulating trimethylamine N-oxide (TMAO), a canonical metabolite from gut flora, has been related to the risk of cardiovascular disorders. However, the association between circulating TMAO and the risk of cardiovascular events has not been quantitatively evaluated. We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating TMAO and subsequent cardiovascular events. Embase and PubMed databases were searched for relevant cohort studies. The overall hazard ratios for the developing of cardiovascular events (CVEs) and mortality were extracted. Heterogeneity among the included studies was evaluated with Cochran's Q Test and I2 statistics. A random-effect model or a fixed-effect model was applied depending on the heterogeneity. Subgroup analysis and meta-regression were used to evaluate the source of heterogeneity. Among the 11 eligible studies, three reported both CVE and mortality outcome, one reported only CVEs and the other seven provided mortality data only. Higher circulating TMAO was associated with a 23% higher risk of CVEs (HR = 1.23, 95% CI: 1.07-1.42, I2 = 31.4%) and a 55% higher risk of all-cause mortality (HR = 1.55, 95% CI: 1.19-2.02, I2 = 80.8%). Notably, the latter association may be blunted by potential publication bias, although sensitivity analysis by omitting one study at a time did not significantly change the results. Further subgroup analysis and meta-regression did not support that the location of the study, follow-up duration, publication year, population characteristics or the samples of TMAO affect the results significantly. Higher circulating TMAO may independently predict the risk of subsequent cardiovascular events and mortality.


cardiovascular events; meta-analysis; mortality; trimethylamine N-oxide

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