Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected functionally relevant coronary artery disease (fCAD).
Cardiovascular death
Functionally relevant coronary artery disease (fCAD)
Gut microbiota
Incident major adverse cardiac events (mace)
Myocardial infarction
Trimethylamine N-oxide (TMAO)
Journal
Clinical research in cardiology : official journal of the German Cardiac Society
ISSN: 1861-0692
Titre abrégé: Clin Res Cardiol
Pays: Germany
ID NLM: 101264123
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
12
05
2021
accepted:
10
02
2022
pubmed:
28
2
2022
medline:
3
6
2022
entrez:
27
2
2022
Statut:
ppublish
Résumé
Trimethylamine 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. Among 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. Concentrations 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]). TMAO 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. NCT01838148.
Sections du résumé
BACKGROUND
BACKGROUND
Trimethylamine 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.
METHODS
METHODS
Among 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.
RESULTS
RESULTS
Concentrations 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]).
CONCLUSION
CONCLUSIONS
TMAO 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 REGISTRATION
BACKGROUND
NCT01838148.
Identifiants
pubmed: 35220448
doi: 10.1007/s00392-022-01992-6
pii: 10.1007/s00392-022-01992-6
pmc: PMC9151506
doi:
Substances chimiques
Methylamines
0
Betaine
3SCV180C9W
trimethyloxamine
FLD0K1SJ1A
Choline
N91BDP6H0X
Carnitine
S7UI8SM58A
Banques de données
ClinicalTrials.gov
['NCT01838148']
Types de publication
Clinical Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
692-704Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL103866
Pays : United States
Informations de copyright
© 2022. The Author(s).
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