Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected functionally relevant coronary artery disease (fCAD)
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Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected functionally relevant coronary artery disease (fCAD). / Amrein, Melissa; Li, Xinmin S; Walter, Joan; Wang, Zeneng; Zimmermann, Tobias; Strebel, Ivo; Honegger, Ursina; Leu, Kathrin; Schäfer, Ibrahim; Twerenbold, Raphael; Puelacher, Christian; Glarner, Noemi; Nestelberger, Thomas; Koechlin, Luca; Ceresa, Benjamin; Haaf, Philip; Bakula, Adam; Zellweger, Michael; Hazen, Stanley L; Mueller, Christian.
In: CLIN RES CARDIOL, Vol. 111, No. 6, 06.2022, p. 692-704.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected functionally relevant coronary artery disease (fCAD)
AU - Amrein, Melissa
AU - Li, Xinmin S
AU - Walter, Joan
AU - Wang, Zeneng
AU - Zimmermann, Tobias
AU - Strebel, Ivo
AU - Honegger, Ursina
AU - Leu, Kathrin
AU - Schäfer, Ibrahim
AU - Twerenbold, Raphael
AU - Puelacher, Christian
AU - Glarner, Noemi
AU - Nestelberger, Thomas
AU - Koechlin, Luca
AU - Ceresa, Benjamin
AU - Haaf, Philip
AU - Bakula, Adam
AU - Zellweger, Michael
AU - Hazen, Stanley L
AU - Mueller, Christian
N1 - © 2022. The Author(s).
PY - 2022/6
Y1 - 2022/6
N2 - 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: 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: 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: 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: NCT01838148.
AB - 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: 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: 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: 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: NCT01838148.
KW - Betaine/metabolism
KW - Cardiovascular Diseases/diagnosis
KW - Carnitine
KW - Choline/metabolism
KW - Coronary Artery Disease/diagnosis
KW - Gastrointestinal Microbiome
KW - Heart Disease Risk Factors
KW - Humans
KW - Methylamines/metabolism
KW - Risk Factors
U2 - 10.1007/s00392-022-01992-6
DO - 10.1007/s00392-022-01992-6
M3 - SCORING: Journal article
C2 - 35220448
VL - 111
SP - 692
EP - 704
JO - CLIN RES CARDIOL
JF - CLIN RES CARDIOL
SN - 1861-0684
IS - 6
ER -
