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
Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Clin Res Cardiol. 2022 Jun;111(6):692-704. doi: 10.1007/s00392-022-01992-6. Epub 2022 Feb 26.
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.
氧化三甲胺（TMAO）与心血管疾病预后相关。然而，尚未评估TMAO及其前体对于功能相关冠状动脉疾病（fCAD）的诊断价值，且在此背景下其预后潜力有待评估。
在1726例疑似fCAD患者中，采用液相色谱串联质谱法定量检测血清TMAO及其前体甜菜碱、胆碱和肉碱。fCAD的诊断通过心肌灌注单光子发射断层扫描（MPI-SPECT）和冠状动脉造影进行，且检测人员对标志物浓度不知情。在5年随访期间评估全因死亡、心血管死亡（CVD）和心肌梗死（MI）事件。
fCAD患者的TMAO、甜菜碱、胆碱和肉碱浓度显著高于无fCAD患者（TMAO：5.33 μM对4.66 μM，p<0.001）；然而，诊断准确性较低（TMAO的受试者工作特征曲线下面积[AUC]：0.56，95%CI[0.53-0.59]，p<0.001）。在预后分析中，高于中位数的TMAO、胆碱和肉碱与5年随访期间死亡和CVD的累积事件显著增加相关（所有p<0.001）。即使在调整肾功能的完整模型中，TMAO仍然是死亡和CVD的显著预测因子（HR = 1.58[1.16, 2.14]，p = 0.003；HR = 1.66[1.07, 2.59]，p = 0.025）。TMAO对死亡和CVD的预后判别准确性良好且稳健（CVD的2年AUC为0.73，95%CI[0.65-0.80]）。
TMAO及其前体甜菜碱、胆碱和肉碱与fCAD显著相关，但诊断价值有限。TMAO是疑似fCAD患者发生死亡和CVD的有力预测因子。
NCT01838148。
