Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-N-oxide in Patients with Heart Failure: Refining the Gut Hypothesis

By W. H. W. Tang, Zeneng Wang, Yiying Fan, B. Levison, Jennie E. Hazen, Lillian M. Donahue, Yuping Wu, S. L. Hazen. Journal of the American College of Cardiology, 2014

670 citations recorded by the source corpus.

BACKGROUND Altered intestinal function is prevalent in patients with heart failure (HF), but its role in adverse outcomes is unclear. OBJECTIVE This study investigated the potential pathophysiologic contributions of intestinal microbiota in HF. METHODS We examined the relationship between fasting plasma trimethylamine-N-oxide (TMAO) and all-cause mortality over 5-year follow-up in 720 stable subjects with HF. RESULTS Median TMAO level was 5.0 μM, which was higher than in non-HF subjects (3.5 -μM; p < 0.001). There was modest but significant correlation between TMAO and B-type natriuretic peptide (BNP) (r = 0.23; p < 0.001). Higher plasma TMAO level was associated with a 3.4-fold increased mortality risk. Following adjustments for traditional risk factors and BNP, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio [HR]: 2.2; 95% confidence interval [CI]: 1.42 to 3.43; p < 0.001), as well as following the addition of estimated glomerular filtration rate to the model (HR: 1.75; 95% CI: 1.07 to 2.86; p < 0.001). CONCLUSION High TMAO levels are observed in patients with HF and elevated TMAO levels portend higher long-term mortality risk independent of traditional risk factors.

Subfields: Biological Psychiatry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a87731b6a941954aa52a9a56166cbd8e61a6e440

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Citations in the corpus

The Gut Microbiota and Inflammation: An Overview (2020, positive): “A similar TMAO and CRP relationship was noted in a different study examining a population of patients with heart failure [121].”
Understanding the Holobiont: How microbial metabolites affect human health and shape the immune system (2017, result): “These observations were further corroborated and extended by subsequent studies from the same group and others (Li et al., 2017; Mente et al., 2015; Tang et al., 2013, 2014, 2015; Trøseid et al., 2015; Wang et al., 2014b).”
Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis (2015, background): “…TMAO levels are associated with risks for both prevalent atherosclerotic heart disease and incident major adverse cardiac events in multiple independent cohorts (Koeth et al., 2013; Lever et al., 2014; Mente et al., 2015; Tang et al., 2013, 2014; Trøseid et al., 2015; Wang et al., 2011, 2014b).”
Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk (2016, neutral): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript studies (Wang et al., 2011; Tang et al., 2013; Tang et al., 2014; Lever et al., 2014; Tang et al., 2015).”
Gut Microbiota in Cardiovascular Health and Disease (2017, background): “In addition to the clear link between TMAO and atherosclerotic CVD risk, TMAO levels have also more recently been linked to heart failure development and poor prognosis in patients with heart failure.(8,22,60,89) We recently observed that circulating TMAO levels are higher in patients with heart fai”