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Cited by 242Gut microbiota and healthAtherosclerosis and Cardiovascular DiseasesNutritional Studies and Diet

Plasma Trimethylamine N -Oxide, a Gut Microbe–Generated Phosphatidylcholine Metabolite, Is Associated With Atherosclerotic Burden

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Senthong, Vichai, Li, Xinmin S., Hudec, Timothy, Coughlin, John, Wu, Yuping, Levison, Bruce, Wang, Zeneng, Hazen, Stanley L. +1 more·2016·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2016.03.546PMC PMC4893167
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Abstract

Background Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is associated with adverse outcomes.Objectives This study sought to examine the relationship between plasma TMAO levels and the complexity and burden of CAD and degree of subclinical myonecrosis.Methods We studied 353 consecutive stable patients with evidence of atherosclerotic CAD detected by elective coronary angiography between 2012 and 2014. Their high-sensitivity cardiac troponin T (hs-cTnT) levels were measured. SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) scores and lesion characteristics were used to quantify atherosclerotic burden. Fasting plasma TMAO was measured by mass spectrometry.Results In this prospective cohort study, the median TMAO level was 5.5 μM (interquartile range [IQR]: 3.4 to 9.8 μM), the median SYNTAX score was 11.0 (IQR: 4.0 to 18.5), and 289 (81.9%), 40 (11.3%), and 24 (6.8%) patients had low (0 to 22), intermediate (23 to 32), and high (≥33) SYNTAX scores, respectively. Plasma TMAO levels correlated (all p < 0.0001) with the SYNTAX score (r = 0.61), SYNTAX score II (r = 0.62), and hs-cTnT (r = 0.29). Adjusting for traditional risk factors, body mass index, medications, lesion characteristic, renal function, and high-sensitivity C-reactive protein, elevated TMAO levels remained independently associated with a higher SYNTAX score (odds ratio [OR]: 4.82; p < 0.0001), SYNTAX score II (OR: 1.88; p = 0.0001), but were not associated with subclinical myonecrosis (OR: 1.14; p = 0.3147). Elevated TMAO level was an independent predictor of the presence of diffuse lesions, even after adjustments for traditional risk factors and for hs-cTnT (OR: 2.05; 95% confidence interval: 1.45 to 2.90; p = 0.0001).Conclusions Fasting plasma TMAO levels are an independent predictor of a high atherosclerotic burden in patients with CAD.

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  • Plasma TMAO was strongly associated with long-term mortality in heart failure patients.

    “Plasma TMAO concentrations were strongly associated with long-term mortality in heart failure patients, with advanced left-ventricular diastolic dysfunction, and with atherosclerosis burden in patients with atherosclerotic coronary artery disease (100, 101, 109, 111, 120).”

    From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [100]

  • Circulating levels of trimethylamine N-oxide associate with cardiovascular disease and predict outcomes in multiple cardiovascular disease phenotypes, including peripheral artery disease, coronary artery disease, acute coronary syndrome, and heart failure.

    “Circulating levels of TMAO have been shown to associate with CVD and predict outcomes in the presence of multiple CVD phenotypes, including peripheral artery disease (PAD)96, coronary artery disease (CAD)97, acute coronary syndrome (ACS)97–99, and heart failure100–104.”

    From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [97]

  • TMAO levels are highly related to coronary atherosclerotic burden and plaque complexity as monitored by the SYNTAX score.

    “In line with these findings, recent studies reveal that TMAO levels are highly related to the coronary atherosclerotic burden and plaque complexity as monitored by the SYNTAX score.19”

    From Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factors (2017) · cites this paper as [19]

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Authors
Senthong, V., Li, X. S., Hudec, T., Coughlin, J., Wu, Y., Levison, B., Wang, Z., Hazen, S. L., & Tang, W. H. W.
Affiliations
  • Cleveland Clinic (US)
  • Cleveland State University (US)
Corresponding author
Tang, W.H. Wilson
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2016-06
Volume
67
Issue
22
Pages
2620-2628
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/j.jacc.2016.03.546
PMC
PMC4893167
OpenAlex
W2408838284
Cited by
242
References
9
Citations by year
2026: 7 · 2025: 10 · 2024: 31 · 2023: 16 · 2022: 37 · 2021: 22 · 2020: 35 · 2019: 26 · 2018: 25 · 2017: 27 · 2016: 6
FWCI
14.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • EngagedScholarship @ Cleveland State University (Cleveland State University) (submittedVersion, cc-by-nc-nd)
Funders
  • Office of Dietary Supplements (R01 HL103866, R01DK106000, P20 HL113452)
  • Pfizer
  • Cleveland Clinic
  • Case Western Reserve University (UL1TR000439)
  • Georgia Clinical and Translational Science Alliance
  • Esperion Therapeutics
  • National Institutes of Health (UL1TR000439)
  • National Heart, Lung, and Blood Institute (R01HL103931, R01HL126827, P20HL113452, P01HL076491, P01HL098055, R01HL130819, R01HL103866)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106000)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords
trimethylamine N-oxide, phosphatidylcholine metabolism, gut microbiota, coronary artery disease, atherosclerotic burden, SYNTAX score, high-sensitivity troponin T, diffuse coronary lesions, coronary angiography, coronary heart disease risk prediction, dyslipidemia
MeSH terms
Aged, Coronary Artery Disease, Female, Humans, Male, Methylamines, Middle Aged, Severity of Illness Index, Mass Spectrometry, Cohort Studies, Biomarkers, Coronary Angiography, Troponin T

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