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J Am Coll Cardiol. 2014 Nov 4;64(18):1908-14. doi: 10.1016/j.jacc.2014.02.617. Epub 2014 Oct 27.

Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis.

Author information

1
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: tangw@ccf.org.
2
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
3
Department of Mathematics, Cleveland State University, Cleveland, Ohio.
4
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.

Abstract

BACKGROUND:

Altered intestinal function is prevalent in patients with heart failure (HF), but its role in adverse outcomes is unclear.

OBJECTIVES:

This study investigated the potential pathophysiological contributions of intestinal microbiota in HF.

METHODS:

We examined the relationship between fasting plasma trimethylamine-N-oxide (TMAO) and all-cause mortality over a 5-year follow-up in 720 patients with stable HF.

RESULTS:

The median TMAO level was 5.0 μM, which was higher than in subjects without HF (3.5 μM; p < 0.001). There was modest but significant correlation between TMAO concentrations and B-type natriuretic peptide (BNP) levels (r = 0.23; p < 0.001). Higher plasma TMAO levels were associated with a 3.4-fold increased mortality risk. Following adjustments for traditional risk factors and BNP levels, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio [HR]: 2.2; 95% 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).

CONCLUSIONS:

High TMAO levels were observed in patients with HF, and elevated TMAO levels portended higher long-term mortality risk independent of traditional risk factors and cardiorenal indexes.

KEYWORDS:

C-reactive protein; TMAO; cardiorenal; intestinal microbiota; mortality

Comment in

PMID:
25444145
PMCID:
PMC4254529
DOI:
10.1016/j.jacc.2014.02.617
[Indexed for MEDLINE]
Free PMC Article

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