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.Graphical abstract
Highlights
During the last decade, translational research has highlighted intestinal microbiota as possible mediators between dietary habits and both the development and progression of coronary artery disease (CAD) [1,2,3,4,5]
EGFR was significantly lower in patients with functionally relevant coronary artery disease (fCAD) and cystatin-C significantly higher in patients with fCAD
Too is the accurate and minimally invasive ability to identify those at increased risk for incident adverse events
Summary
Translational research has highlighted intestinal microbiota as possible mediators between dietary habits and both the development and progression of coronary artery disease (CAD) [1,2,3,4,5]. Recent studies have documented an association between plasma TMAO concentration and the risk of death, myocardial infarction (MI), and stroke in patients with either stable CAD or acute coronary syndromes [1, 2, 4, 10, 20,21,22]. 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. 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
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