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Eur J Intern Med. 2016 Dec;36:67-73. doi: 10.1016/j.ejim.2016.08.017. Epub 2016 Aug 24.

Trimethylamine-N-oxide (TMAO) predicts fatal outcomes in community-acquired pneumonia patients without evident coronary artery disease.

Author information

1
University Department of Internal Medicine, Kantonsspital Aarau, Switzerland. Electronic address: manuel.ottiger@gmx.net.
2
University Department of Internal Medicine, Kantonsspital Aarau, Switzerland. Electronic address: manuela.nickler@ksa.ch.
3
Department of Laboratory Medicine, Kantonsspital Aarau, Switzerland. Electronic address: christian.steuer@pharma.ethz.ch.
4
University Department of Internal Medicine, Kantonsspital Aarau, Switzerland. Electronic address: jonas.odermatt@ksa.ch.
5
Department of Laboratory Medicine, Kantonsspital Aarau, Switzerland. Electronic address: andreas.huber@ksa.ch.
6
Endocrinology, Diabetology and Metabolism, University Hospital Basel, Switzerland. Electronic address: mirjam.christ@usb.ch.
7
Department of Internal Medicine, Kantonsspital Luzern, Switzerland. Electronic address: christoph.henzen@luks.ch.
8
Department of Internal Medicine, Kantonsspital Münsterlingen, Switzerland. Electronic address: claus.hoess@stgag.ch.
9
Department of Internal Medicine, Bürgerspital Solothurn, Switzerland. Electronic address: endodiab.bss@bluewin.ch.
10
Department of Internal Medicine, Kantonsspital Liestal, Switzerland. Electronic address: werner.zimmerli@unibas.ch.
11
University Department of Internal Medicine, Kantonsspital Aarau, Switzerland. Electronic address: happy.mueller@unibas.ch.
12
University Department of Internal Medicine, Kantonsspital Aarau, Switzerland. Electronic address: schuetzph@gmail.com.

Abstract

INTRODUCTION:

The pro-atherosclerotic metabolite trimethylamine-N-oxide (TMAO) is a risk factor for incident cardiovascular events and a potentially modifiable mediator of chronic inflammation through broad-spectrum antibiotic treatment by changing the microbiome. Whether TMAO is associated with adverse clinical outcomes in acute inflammatory community-acquired pneumonia (CAP) patients is unknown.

METHODS:

A total of 317 CAP patients from a previous Swiss multicenter trial were prospectively followed for a median of 6.1years. TMAO plasma levels were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We used Cox regression models to investigate associations between baseline TMAO levels and all-cause mortality.

RESULTS:

Six-year mortality was 45.1%, and 18.9% of the patients had coronary artery disease (CAD). Median admission TMAO (μmolL-1) levels were significantly higher in non-survivors compared to survivors (4.1 [interquartile range (IQR), 2.2-7.2] vs. 2.5 [IQR, 1.5-4.1]; p<0.001). A strong association between TMAO and 6-year all-cause mortality was found for patients without CAD (adjusted hazard ratio (HR) 1.9 ([95% CI 1.2-3.1]; p<0.05). In patients with known CAD, no such association was found (adjusted HR 0.6 (0.2-1.6); p=0.309, interaction p=0.009). In patients without antibiotic pretreatment receiving antibiotic treatment, TMAO significantly decreased from admission to day seven (median, 3.9 [IQR, 2.1-7.5] vs. 3.1 [IQR, 1.4-6.6]; p<0.01).

CONCLUSIONS:

TMAO is associated with long-term fatal outcomes in CAP patients without evident CAD and modifiable through antibiotic treatment. Whether chronic modulation of TMAO by targeting the microbiome reduces mortality risk needs to be evaluated in future interventional trials.

KEYWORDS:

Biomarker; Community-acquired pneumonia; Coronary artery disease; Mortality prediction; Trimethylamine-N-oxide

PMID:
27567042
DOI:
10.1016/j.ejim.2016.08.017
[Indexed for MEDLINE]

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