Trimethylamine-N-oxide has prognostic value in coronary heart disease: a meta-analysis and dose-response analysis

Yao, Miao-En; Liao, Pengda; Zhao, Xiaobo; Wang, Lei

doi:10.1186/s12872-019-01310-5

Cited by 64 publications

(56 citation statements)

References 40 publications

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“…In our study plasma TMAO was negatively associated with the presence of soft plaque, total plaque burden, and calcified plaque burden in univariate and multivariable models after adjusting for age, sex, and traditional risk factors. Whilst this finding contrasts with some prior studies that have found TMAO is associated with increased incidence of major adverse cardiovascular events in patients with established CAD, peripheral artery disease or chronic kidney disease, it is in keeping with other studies that have not confirmed an association with CAD and have suggested there may be a more nuanced relationship [ 39 , 40 , 41 ]. TMAO is generated through the oxidation of trimethylamine (TMA) by TMA monooxygenase present in some gut microbiota [ 42 ].…”

Section: Discussioncontrasting

confidence: 84%

Metabolic Signatures in Coronary Artery Disease: Results from the BioHEART-CT Study

Vernon

Tang

Kim

et al. 2021

Cells

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Despite effective prevention programs targeting cardiovascular risk factors, coronary artery disease (CAD) remains the leading cause of death. Novel biomarkers are needed for improved risk stratification and primary prevention. To assess for independent associations between plasma metabolites and specific CAD plaque phenotypes we performed liquid chromatography mass-spectrometry on plasma from 1002 patients in the BioHEART-CT study. Four metabolites were examined as candidate biomarkers. Dimethylguanidino valerate (DMGV) was associated with presence and amount of CAD (OR) 1.41 (95% Confidence Interval [CI] 1.12–1.79, p = 0.004), calcified plaque, and obstructive CAD (p < 0.05 for both). The association with amount of plaque remained after adjustment for traditional risk factors, ß-coefficient 0.17 (95% CI 0.02–0.32, p = 0.026). Glutamate was associated with the presence of non-calcified plaque, OR 1.48 (95% CI 1.09–2.01, p = 0.011). Phenylalanine was associated with amount of CAD, ß-coefficient 0.33 (95% CI 0.04–0.62, p = 0.025), amount of calcified plaque, (ß-coefficient 0.88, 95% CI 0.23–1.53, p = 0.008), and obstructive CAD, OR 1.84 (95% CI 1.01–3.31, p = 0.046). Trimethylamine N-oxide was negatively associated non-calcified plaque OR 0.72 (95% CI 0.53–0.97, p = 0.029) and the association remained when adjusted for traditional risk factors. In targeted metabolomic analyses including 53 known metabolites and controlling for a 5% false discovery rate, DMGV was strongly associated with the presence of calcified plaque, OR 1.59 (95% CI 1.26–2.01, p = 0.006), obstructive CAD, OR 2.33 (95% CI 1.59–3.43, p = 0.0009), and amount of CAD, ß-coefficient 0.3 (95% CI 0.14–0.45, p = 0.014). In multivariate analyses the lipid and nucleotide metabolic pathways were both associated with the presence of CAD, after adjustment for traditional risk factors. We report novel associations between CAD plaque phenotypes and four metabolites previously associated with CAD. We also identified two metabolic pathways strongly associated with CAD, independent of traditional risk factors. These pathways warrant further investigation at both a biomarker and mechanistic level.

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Section: Discussioncontrasting

confidence: 84%

Metabolic Signatures in Coronary Artery Disease: Results from the BioHEART-CT Study

Vernon

Tang

Kim

et al. 2021

Cells

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“…Three recent meta-analyses have established that elevated TMAO blood levels are related with increased CVD risks and all-cause mortality [98,102,103], nevertheless, some criticism exists about the TMAO and CVD relationship because fish could contain high concentrations of TMAO and TMA [104]. However, fish consumption is related with heart health [105][106][107].…”

Section: Diet Gut Microbiota and Cardiovascular Diseasesmentioning

confidence: 99%

The Gut Microbiota and Its Implication in the Development of Atherosclerosis and Related Cardiovascular Diseases

et al. 2020

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The importance of gut microbiota in health and disease is being highlighted by numerous research groups worldwide. Atherosclerosis, the leading cause of heart disease and stroke, is responsible for about 50% of all cardiovascular deaths. Recently, gut dysbiosis has been identified as a remarkable factor to be considered in the pathogenesis of cardiovascular diseases (CVDs). In this review, we briefly discuss how external factors such as dietary and physical activity habits influence host-microbiota and atherogenesis, the potential mechanisms of the influence of gut microbiota in host blood pressure and the alterations in the prevalence of those bacterial genera affecting vascular tone and the development of hypertension. We will also be examining the microbiota as a therapeutic target in the prevention of CVDs and the beneficial mechanisms of probiotic administration related to cardiovascular risks. All these new insights might lead to novel analysis and CVD therapeutics based on the microbiota.

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“…Surprisingly, TML levels were only 0.47 µmol/L in acute stroke patients and significantly lower compared with healthy controls. Our findings argue against a linear relationship of TML with vascular disease, but rather suggests a J-shaped relationship similar to TMAO with MACE (Yao et al 2020). Although we also observed higher TML levels in acute stroke patients with prevalent cardiovascular disease, the mean TML level for all patients with cerebral ischemia are of the lowest reported, so far.…”

Section: Discussionmentioning

confidence: 52%

Trimethyllysine, vascular risk factors and outcome in acute ischemic stroke (MARK–STROKE)

et al. 2021

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Trimethyllysine (TML) is involved in the generation of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO) by gut microbiota. In clinical studies, elevated TML levels predicted major adverse cardiovascular events (MACE) in patients with acute or stable coronary artery disease (CAD). In contrast to cardiovascular patients, the role of TML in patients with acute cerebral ischemia is unknown. Here, we evaluated circulating TML levels in 374 stroke patients from the prospective biomarkers in stroke (MARK-STROKE) study. Compared with 167 matched healthy controls, acute ischemic stroke patients had lower median TML plasma concentrations, i.e. 0.71 vs. 0.47 µmol/L (p < 0.001) and this difference persisted after adjusting for age and sex. TML plasma concentrations were associated with age, serum creatinine, glucose, cholesterol and lysine. Patients with prevalent arterial hypertension, atrial fibrillation or a history of myocardial infarction had increased TML levels, but this observation was not independent of age, sex and GFR. In 274 patients, follow-up data were available. During a median follow-up of 284 [25th-75th percentile: 198, 431] days, TML was not associated with incident MACE (stroke, myocardial infarction, death). In summary, our data suggests a different role of TML in acute ischemic stroke compared with CAD patients.

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Trimethylamine-N-oxide has prognostic value in coronary heart disease: a meta-analysis and dose-response analysis

Cited by 64 publications

References 40 publications

Metabolic Signatures in Coronary Artery Disease: Results from the BioHEART-CT Study

Metabolic Signatures in Coronary Artery Disease: Results from the BioHEART-CT Study

The Gut Microbiota and Its Implication in the Development of Atherosclerosis and Related Cardiovascular Diseases

Trimethyllysine, vascular risk factors and outcome in acute ischemic stroke (MARK–STROKE)

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