Trimethylamine (Tma) And Trimethylamine-N-Oxide (Tmao) As Predictors Of Cardiovascular Mortality In Peripheral Artery Disease

Roncal, Carlos Guilhermo Piscoya; Martínez-Aguilar, E.; Orbe, Josune; Ravassa, Susana; Fernández-Montero, Alejandro; Pipaon, G. Saenz De; Ugarte, Andrés Varela de; Mendoza, Ander Estella-Hermoso de; Rodríguez, Jairo; Fernández-Alonso, S.; Fernández-Alonso, Leopoldo; Oyarzabal, Jorge Rivas; Paramo, J.A.

doi:10.1016/j.atherosclerosis.2019.06.716

Cited by 3 publications

(6 citation statements)

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“…Fourth , in contrast, concentrations of TMAO, carnitine and to a lesser extent choline were significant predictors of incident adverse events including either MI, CV-death, or all cause death. This finding is in concordance with previous reports where TMAO has been shown to be associated with all-cause and CV-death [ 1 , 2 , 4 , 10 , 20 – 22 ]. Moreover, significantly more adverse events (all-cause or CV death, or AMI) occurred in patients with high TMAO in combination with a hs-cTnT above the URL, a quantitative marker of cardiomyocyte injury strongly associated with future CV-death [ 23 , 49 ].…”

Section: Discussionsupporting

confidence: 94%

“…Fifth , time-dependent ROC curve analysis showed consistent moderate-to-good prognostic accuracy of TMAO and its precursors for all-cause and CV-death during follow-up. The prognostic value for TMAO persisted also in fully adjusted models, highlighting possible implications for routine clinical practice given similar observations in recent studies [ 4 , 20 , 27 , 36 ]. Overall, the prognostic accuracy for all-cause and CV-death was highest and most consistent for TMAO, and slightly lower and less consistent for its precursors and other outcomes.…”

Section: Discussionsupporting

confidence: 75%

“…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]. The consumption of red-meat and dairy products rich in choline, betaine, carnitine, and trimethyllysine leads to the production of trimethylamine (TMA) by certain intestinal microbiota [1,6,7].…”

Section: Introductionmentioning

confidence: 99%

“…TMAO was indicated in multiple studies to accelerate atherosclerosis and enhance platelet reactivity as well as thrombosis potential [3,[17][18][19]]. In addition, 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].…”

Section: Introductionmentioning

confidence: 99%

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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

Walter

et al. 2022

Clin Res Cardiol

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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. Graphical abstract

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Amrein

Walter

et al. 2022

Clin Res Cardiol

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“…Once TMA is produced, most TMA is oxidized into TMAO in the liver predominantly by the enzyme flavin-containing monooxygenase 3 ( 37 ). Some clinical studies have investigated the role of TMAO in predicting the prognostic outcomes and mortality of diverse diseases ( 38 – 40 ). In addition to its predictive value, TMAO has been implicated in the pathogenesis of various human diseases, including cardiovascular ( 41 ), kidney ( 42 ), metabolic ( 43 ) and neurological ( 44 ) disorders.…”

Section: Introductionmentioning

confidence: 99%

Roles of Gut Microbial Metabolites in Diabetic Kidney Disease

et al. 2021

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Diabetes is a highly prevalent metabolic disease that has emerged as a global challenge due to its increasing prevalence and lack of sustainable treatment. Diabetic kidney disease (DKD), which is one of the most frequent and severe microvascular complications of diabetes, is difficult to treat with contemporary glucose-lowering medications. The gut microbiota plays an important role in human health and disease, and its metabolites have both beneficial and harmful effects on vital physiological processes. In this review, we summarize the current findings regarding the role of gut microbial metabolites in the development and progression of DKD, which will help us better understand the possible mechanisms of DKD and explore potential therapeutic approaches for DKD.

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Diet, Trimethylamine Metabolism, and Mitochondrial DNA: An Observational Study

Bordoni

Malinowska

Petracci

et al. 2022

Molecular Nutrition Food Res

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Scope: Mitochondrial DNA copy number (mtDNAcn) and its methylation level in the D-loop area have been correlated with metabolic health and are suggested to vary in response to environmental stimuli, including diet. Circulating levels of trimethylamine-n-oxide (TMAO), which is an oxidative derivative of the trimethylamine (TMA) produced by the gut microbiome from dietary precursors, have been associated with chronic diseases and are suggested to have an impact on mitochondrial dynamics. This study is aimed to investigate the relationship between diet, TMA, TMAO, and mtDNAcn, as well as DNA methylation. Methods and results: Two hundred subjects with extreme (healthy and unhealthy) dietary patterns are recruited. Dietary records are collected to assess their nutrient intake and diets' quality (Healthy Eating Index). Blood levels of TMA and TMAO, circulating levels of TMA precursors and their dietary intakes are measured. MtDNAcn, nuclear DNA methylation long interspersed nuclear element 1 (LINE-1), and strand-specific D-loop methylation levels are assessed. There is no association between dietary patterns and mtDNAcn. The TMAO/TMA ratio is negatively correlated with d-loop methylation levels but positively with mtDNAcn. Conclusions: These findings suggest a potential association between TMA metabolism and mitochondrial dynamics (and mtDNA), indicating a new avenue for further research.

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Trimethylamine (Tma) And Trimethylamine-N-Oxide (Tmao) As Predictors Of Cardiovascular Mortality In Peripheral Artery Disease

Cited by 3 publications

References 0 publications

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

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

Roles of Gut Microbial Metabolites in Diabetic Kidney Disease

Diet, Trimethylamine Metabolism, and Mitochondrial DNA: An Observational Study

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