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

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Qi, Jiaqian, You, Tao, Li, Jing, Pan, Tingting, Xiang, Li, Han, Yue, Zhu, Li·2018·Journal of Cellular and Molecular Medicine
DOI 10.1111/jcmm.13307PMC PMC5742728
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Abstract

Abstract 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.

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  • Elevated circulating TMAO levels are associated with both CVD and mortality risks across multiple cohorts and continents, supporting clinical prognostic value.

    “Notably, a clinical prognostic value of TMAO has been supported by multiple meta-analyses reaffirming that elevated circulating TMAO levels are associated with both CVD and mortality risks across multiple cohorts and continents.[10][11][12]”

    From Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women (2019) · cites this paper as [11]

  • Meta-analyses confirm a strong clinical association between increased TMAO levels and incident adverse cardiovascular events and mortality risks in multiple populations.

    “several recent meta-analyses confirm a strong clinical association between increased levels of TMAO and incident adverse cardiovascular event and mortality risks in multiple populations25–27.”

    From Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential (2018) · cites this paper as [27]

  • Meta-analyses have concluded that a strong relationship exists between elevated circulating trimethylamine N-oxide levels and both cardiovascular disease risk and mortality in multiple cohorts on different continents.

    “While not all studies have observed the relationship between heightened TMAO levels and incident CVD risks, examination of extant clinical studies with TMAO in multiple meta-analyses have concluded that a strong relationship indeed exists between elevated circulating TMAO levels and both CVD risk and mortality in multiple cohorts on different continents105–107.”

    From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [106]

  • These observations have been replicated in multiple independent observational cohorts across a spectrum of CKD patients.

    “These observations have since been replicated in multiple independent observational cohorts across a spectrum of CKD patients199–203.”

    From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [202]

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Cited by

Sorted by citations

Authors
Qi, J., You, T., Li, J., Pan, T., Xiang, L., Han, Y., & Zhu, L.
Affiliations
  • Soochow University (CN)
  • First Affiliated Hospital of Soochow University (CN)
  • Department of Cardiology The Second Affiliated Hospital of Soochow University Suzhou China
Corresponding author
  • Han, Yue
  • Zhu, Li
ORCID
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2017-08-07
Volume
22
Issue
1
Pages
185-194
ISSN
  • 1582-1838 (ISSN-L)
  • 1582-4934
DOI
10.1111/jcmm.13307
PMC
PMC5742728
OpenAlex
W2744560242
Cited by
268
References
7
Citations by year
2026: 22 · 2025: 31 · 2024: 25 · 2023: 25 · 2022: 36 · 2021: 48 · 2020: 36 · 2019: 24 · 2018: 20 · 2017: 1
FWCI
2.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81620108001, 81370373, 81270591, 81670132, 91439112)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
Keywords
trimethylamine N-oxide, cardiovascular events, all-cause mortality, gut microbiota metabolites, cardiovascular risk prediction, prospective cohort
MeSH terms
Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Humans, Male, Methylamines, Middle Aged, Prospective Studies, Risk Factors

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