The Medical journal of AustraliaSep 22, 2020

Gut bacteria chemical trimethylamine N-oxide linked to worse outcomes in heart failure patients

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 3, 2026

Abstract

In a meta-analysis of seven studies with 6,879 heart failure patients, higher plasma TMAO levels were associated with a 1.68-fold increased risk of major adverse cardiac events.

Higher plasma TMAO concentration is linked to increased risk of all-cause mortality (1.67-fold increase for highest TMAO tertile).
The association between TMAO levels and risks of major adverse cardiac events and mortality persisted after adjusting for multiple risk factors.
Greater TMAO levels correlate with poorer prognoses in heart failure patients, independent of renal function in some cases.
Significant variability was observed in studies adjusting for kidney function, indicating potential differences in patient populations or methodologies.

Simplified

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 (I = 76%). 2

CONCLUSIONS: Elevated plasma TMAO level in patients with heart failure is associated with poorer prognoses. This association is only partially mediated by renal dysfunction.

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Gut bacteria chemical trimethylamine N-oxide linked to worse outcomes in heart failure patients

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