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Updated: Dec 8, 2025
Murine Fecal Isolation and Microbiota Transplantation
Published on: May 26, 2023
Gut microbiota-derived trimethylamine N-oxide is associated with poor prognosis in patients with heart failure
Wensheng Li1, Anqing Huang1, Hailan Zhu1
1Shunde Hospital of Southern Medical University, Foshan (Guangdong), China.
Objective:
Gut microbiota-produced trimethylamine N-oxide (TMAO) is a risk factor for cardiovascular events. However, conflicting findings regarding the link between plasma TMAO level and prognosis for patients with heart failure have been reported. We examined the association of plasma TMAO concentration with risk of major adverse cardiac events (MACEs) and all-cause mortality in patients with heart failure.
Study Design:
Meta-analysis of prospective clinical studies.
Data Sources:
We searched electronic databases (PubMed, EMBASE) for published prospective studies examining associations between plasma TMAO level and MACEs and all-cause mortality in adults with heart failure.
Data Synthesis:
Hazard ratios (HRs) with 95% confidence intervals for associations between TMAO level and outcomes were estimated in random effects models. In seven eligible studies including a total of 6879 patients (median follow-up, 5.0 years) and adjusted for multiple risk factors, higher plasma TMAO level was associated with greater risks of MACEs (TMAO tertile 3 v tertile 1: HR, 1.68; 95% CI, 1.44-1.96; per SD increment: HR, 1.26; 95% CI, 1.18-1.36) and of all-cause mortality (TMAO tertile 3 v tertile 1: HR, 1.67; 95% CI, 1.17-2.38; per SD increment: HR, 1.26; 95% CI, 1.07-1.48). Higher TMAO level was also associated with greater risk of MACEs after adjusting for estimated glomerular filtration rate (eGFR; six studies included); however, the heterogeneity of studies in which risk was adjusted for eGFR was significant (I2 = 76%).
Conclusions:
Elevated plasma TMAO level in patients with heart failure is associated with poorer prognoses. This association is only partially mediated by renal dysfunction.
Insights
Higher trimethylamine N-oxide (TMAO) levels in heart failure patients predict worse outcomes, including major adverse cardiac events and death. This link is partly explained by kidney function but remains significant overall.
Area of Science:
- Cardiology
- Metabolomics
- Renal Medicine
Background:
- Gut microbiota-derived trimethylamine N-oxide (TMAO) is implicated in cardiovascular disease.
- Previous studies on TMAO's prognostic value in heart failure patients have yielded conflicting results.
Purpose of the Study:
- To investigate the association between plasma TMAO concentration and the risk of major adverse cardiac events (MACEs) and all-cause mortality in heart failure patients.
Main Methods:
- A meta-analysis of seven prospective clinical studies was conducted.
- Data from 6879 heart failure patients with a median follow-up of 5.0 years were analyzed.
- Hazard ratios (HRs) were estimated using random-effects models, adjusting for multiple risk factors and, in some analyses, estimated glomerular filtration rate (eGFR).
Main Results:
- Elevated plasma TMAO levels were significantly associated with increased risks of MACEs (HR, 1.68; 95% CI, 1.44-1.96 for highest vs. lowest tertile) and all-cause mortality (HR, 1.67; 95% CI, 1.17-2.38 for highest vs. lowest tertile).
- These associations persisted after adjusting for eGFR, although significant heterogeneity was observed in eGFR-adjusted analyses (I² = 76%).
Conclusions:
- Higher plasma TMAO levels are linked to poorer prognosis in heart failure patients.
- Renal dysfunction partially mediates this association but does not fully explain the observed prognostic value of TMAO.
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