Increased plasma trimethylamine- N -oxide is associated with incident atrial fibrillation

Svingen, Gard Frodahl Tveitevåg; Zuo, Hui; Ueland, Per Magne; Seifert, Reinhard; Løland, Kjetil Halvorsen; Pedersen, Eva Ringdal; Schuster, Peter; Karlsson, Therese; Tell, Grethe S.; Schartum-Hansen, Hall; Olset, Hilde; Svenningsson, Mads Malm; Strand, Elin; Nilsen, Dennis W.T.; Nordrehaug, Jan Erik; Dhar, Indu; Nygård, Ottar

doi:10.1016/j.ijcard.2018.04.128

Cited by 79 publications

(81 citation statements)

References 33 publications

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“…The flowchart of the literature search and study selection is presented in Figure S1. From these studies, six studies were cohort, five were cross‐sectional, and one was a nested‐case‐control study . The studies were independently analysed according to design, disease status, and TMAO sample type (plasma or serum).…”

Section: Resultsmentioning

confidence: 99%

“…However, all included studies for dose‐response meta‐analysis were performed in plasma samples except for the study by Stubbs et al; therefore, subgrouping according to TMAO sample source was not possible to perform. In total, five studies were included for dose‐response meta‐analysis of the association between TMAO and BMI while the Svingen GFT study was included as two independent studies. The characteristics of included studies are presented in Table .…”

Section: Resultsmentioning

confidence: 99%

“…When the number of individuals in each category of TMAO were not provided in the manuscript, we assumed that equal numbers of participants were enrolled in each group. A study by Svingen et al with two different protocols and results (Western Norway Coronary Angiography Cohort [WECAC] and community‐based Hordaland Health Study [HUSK]) were analysed as two independent studies in our analysis.…”

Section: Methodsmentioning

confidence: 99%

“…The included studies analysed healthy individuals, patients with CVD, cohort, and cross‐sectional studies separately. Therefore, five studies were included while the study by Svingen et al was included as two independent studies. The median point in each TMAO category was also identified.…”

Section: Methodsmentioning

confidence: 99%

“…TMAO substrate metabolites are abundant in foods rich in carnitine, choline, and lecithin, including egg yolks, milk, dairy products, organ and muscle meats, and seafood such as mollusks, crustaceans, and fish . Recently, several studies have found a possible role for TMAO in chronic disease including CVD and mortality diabetes, chronic kidney disease and metabolic syndrome . In a cross‐sectional study among 1286 Canadians, the highest quintile of serum TMAO was associated with increased prevalent CVD after adjustment for potential confounders (OR, 9.33; CI, 1.88‐46.37; P = .006).…”

Section: Introductionmentioning

confidence: 99%

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Gut microbiota‐derived metabolite trimethylamine N‐oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose‐response meta‐ analysis

et al. 2020

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Summary It has been suggested that trimethylamine N‐oxide (TMAO) is associated with increased risk of diabetes and cardiovascular disease (CVD) morbidity and mortality. However, it is not known whether increased TMAO concentrations is associated with obesity. In the current study, we summarized the evidence related to the association of circulating TMAO with the risk of obesity measurements, including body mass index (BMI), waist circumference (WC), and waist‐to‐hip ratio (WHR) in a two‐class and dose‐response meta‐analysis of observational studies. A systematic search carried out in PubMed, SCOPUS, Cochrane, and ProQuest through September 30, 2019 resulted in 12 eligible studies which were included in the current meta‐synthesis. In these studies, BMI was reported but there were no reports of WC or WHR. Meta‐analysis of two‐class variables and dose‐response meta‐analysis of continuous variables were performed. Subgroup analysis and meta‐regression were also performed to identify the source of heterogeneity. There was a dose‐response association between circulating TMAO concentration and increased BMI in studies involving healthy individuals (P nonlinearity = .007), while no evidence of departure from linearity was observed according to study design or among patients with CVD. Results showed the highest category of TMAO was associated with 0.56 kg/m2 increase in BMI (weighted mean difference [WMD], 0.563; CI, 0.026‐1.100; P = .04). The results of the current meta‐analysis revealed a positive association between circulating TMAO and obesity as presented by increased BMI. Moreover, a dose‐dependent association between circulating TMAO and obesity was also identified in apparently healthy individuals. This is the first meta‐analysis to reveal positive dose‐dependent associations between circulating TMAO concentration and obesity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gut microbiota‐derived metabolite trimethylamine N‐oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose‐response meta‐ analysis

et al. 2020

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Human Gut Microbiota in Cardiovascular Disease

Ronen,

Rokach,

Abedat

et al. 2024

Comprehensive Physiology

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The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N ‐oxide (TMAO), short‐chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449‐5490, 2024.

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Trimethylamine N‐oxide as a risk marker for ischemic stroke in patients with atrial fibrillation

Liang

Dong

Guo

et al. 2018

J Biochem & Molecular Tox

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Trimethylamine N-oxide (TMAO) is an independent risk factor of cardiovascular disease. Our objective was to explore the relation between TMAO and ischemic stroke (IS) in patients with atrial fibrillation (AF). A total of 68 patients with AF with IS and 111 ones without IS were enrolled. The plasma levels of TMAO remarkably increased in IS-AF patients (8.25 ± 1.58 µM) compared with patients with AF (2.22 ± 0.09 µM, P < 0.01). The receiver operating characteristic analysis revealed that the best cutoff value of TMAO to predict IS in patients with AF was 3.53 µM with 75.0% sensitivity and 92.8% specificity (area under the curve: 0.917, 95% confidence intervals: 0.877-0.957). Univariate and multivariate logistic regression analysis showed that TMAO was an independent predictor in IS. The level of TMAO was correlated with the CHA2DS2-VASc score. In conclusion, TMAO was an independent predictor of IS, which could potentially refine stroke stratification in patients with AF.

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Increased plasma trimethylamine- N -oxide is associated with incident atrial fibrillation

Cited by 79 publications

References 33 publications

Gut microbiota‐derived metabolite trimethylamine N‐oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose‐response meta‐ analysis

Gut microbiota‐derived metabolite trimethylamine N‐oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose‐response meta‐ analysis

Human Gut Microbiota in Cardiovascular Disease

Trimethylamine N‐oxide as a risk marker for ischemic stroke in patients with atrial fibrillation

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