Evidence map›Paper›PMID 35220448›Full record

Observational studyClinical research in cardiology : official journal of the German Cardiac Society2022

Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected functionally relevant coronary artery disease (fCAD).

Melissa Amrein, Xinmin S Li, Joan Walter, Zeneng Wang, Tobias Zimmermann, Ivo Strebel, Ursina Honegger, Kathrin Leu, Ibrahim Schäfer, Raphael Twerenbold and 10 more

Registry-linked trialOpen access · hybridAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Clinical research in cardiology : official journal of the German Cardiac Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01838148 (BASEL VIII Trial - Biochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia), which is not on this map. Cited by 22 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 2 pooled it
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01838148 recruitingnot on this map

BASEL VIII Trial - Biochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia

TypeobservationalSponsorUniversity Hospital, Basel, SwitzerlandRan2004 to 2025Enrolled4,000ConditionsCoronary Artery Disease, Angina, Stable, Exercise Test, Biological Markers
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.

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  9. Trimethylamine-Annals of medicine · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 4 countries.

Melissa Amrein *Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.ORCID http://orcid.org/0000-0003-4522-0894
Xinmin S Li *Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Joan WalterDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Zeneng WangDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Tobias ZimmermannDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Ivo StrebelDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Ursina HoneggerDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Kathrin LeuDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Ibrahim SchäferDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Raphael TwerenboldDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Christian PuelacherDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Noemi GlarnerDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Thomas NestelbergerDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Luca KoechlinDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Benjamin CeresaDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Philip HaafDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Adam BakulaDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Michael ZellwegerDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Stanley L HazenDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Christian MuellerDepartment of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland. christian.mueller@usb.ch.
University of Basel · CHCleveland Clinic Lerner College of Medicine · USCleveland Clinic · USUniversity of British Columbia · CA

Funding

Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
NHLBI NIH HHS R01 HL103866
6 · The paper itself

Abstract

backgroundTrimethylamine N-oxide (TMAO) has been associated with cardiovascular outcomes. However, the diagnostic value of TMAO and its precursors have not been assessed for functionally relevant coronary artery disease (fCAD) and its prognostic potential in this setting needs to be evaluated.

methodsAmong 1726 patients with suspected fCAD serum TMAO, and its precursors betaine, choline and carnitine, were quantified using liquid chromatography tandem mass spectrometry. Diagnosis of fCAD was performed by myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography blinded to marker concentrations. Incident all-cause death, cardiovascular death (CVD) and myocardial infarction (MI) were assessed during 5-years follow-up.

resultsConcentrations of TMAO, betaine, choline and carnitine were significantly higher in patients with fCAD versus those without (TMAO 5.33 μM vs 4.66 μM, p < 0.001); however, diagnostic accuracy was low (TMAO area under the receiver operating curve [AUC]: 0.56, 95% CI [0.53-0.59], p < 0.001). In prognostic analyses, TMAO, choline and carnitine above the median were associated with significantly (p < 0.001 for all) higher cumulative events for death and CVD during 5-years follow-up. TMAO remained a significant predictor for death and CVD even in full models adjusted for renal function (HR = 1.58 (1.16, 2.14), p = 0.003; HR = 1.66 [1.07, 2.59], p = 0.025). Prognostic discriminative accuracy for TMAO was good and robust for death and CVD (2-years AUC for CVD 0.73, 95% CI [0.65-0.80]).

conclusionTMAO and its precursors, betaine, choline and carnitine were significantly associated with fCAD, but with limited diagnostic value. TMAO was a strong predictor for incident death and CVD in patients with suspected fCAD. CLINICAL

trial registrationNCT01838148.

Indexed as

Cardiovascular DiseasesCoronary Artery DiseaseGastrointestinal MicrobiomeBetaineCarnitineCholineHeart Disease Risk FactorsHumansMethylaminesRisk FactorsBetaineCarnitineCholineMethylaminestrimethyloxamineCardiovascular deathFunctionally relevant coronary artery disease (fCAD)Gut microbiotaIncident major adverse cardiac events (mace)Myocardial infarctionTrimethylamine N-oxide (TMAO)

Identifiers

PMID35220448
PMCPMC9151506
OpenAlexW4214700498

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.