Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study

Guasch‐Ferré, Marta; Hu, Frank B.; Ruíz-Canela, Miguel; Bulló, Mònica; Toledo, Estefanía; Wang, Dong D.; Corella, Dolores; Gómez‐Gracia, Enrique; Fiol, Miquel; Estruch, Ramón; Lapetra, José; Fitó, Montserrat; Arós, Fernando; Serra‐Majem, Lluís; Ros, Emilio; Dennis, Courtney; Liang, Liming; Clish, Clary B.; Martínez‐González, Miguel A.; Salas‐Salvadó, Jordi

doi:10.1161/jaha.117.006524

Cited by 108 publications

(94 citation statements)

References 46 publications

(125 reference statements)

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“…Chronic consumption of diets rich in red meat increased both plasma and urine TMAO levels (21). In this study of a Chinese population, the median of TMAO levels was 1.45 µmol/L (interquartile range: 0.94-2.32), which was lower than that in western populations (7,22,23), and similar to that in another study conducted in Chinese populations (24).…”

Section: Discussionsupporting

confidence: 75%

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Circulating metabolites from the choline pathway and acute coronary syndromes in a Chinese case-control study

Dai

Tian

et al. 2020

Preprint

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Background Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consumes a different dietary pattern than their Western counterparts. Methods We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. Results After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.78(1.45-2.21)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 2.24 (1.36-3.71), p <0.001 for trend]. Per 1-SD increment in metabolite score was positively associated with higher odds of ACS [OR (95% CI), 1.76 (1.44-2.17)], and per 1-SD increment in the betaine/choline ratio was inversely associated with the odds of ACS [OR (95% CI), 0.49 (0.39-0.60)]. Conclusions Among our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese.

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Section: Discussionsupporting

confidence: 75%

“…As the metabolic precursors of TMAO, choline (the precursor of betaine) and betaine have also been linked with the risk of CVD in several studies (23,(28)(29)(30)(31). The major fate of dietary choline is conversion to phosphatidylcholine, which is essential in the secretion of very-low-density lipoproteins from the liver (32).…”

Section: Discussionmentioning

confidence: 99%

Circulating metabolites from the choline pathway and acute coronary syndromes in a Chinese case-control study

Dai

Tian

et al. 2020

Preprint

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“…Metabolites related to the choline pathway were identified in several studies in synovial tissue, synovial fluid, and blood (serum/plasma) samples in both animal models and human studies. Diet is the main source of choline [162], whose metabolites (trimethylamine-N-oxide, TMAO) have already been related with cardiovascular inflammation [121,163]. Choline and other dietary trimethylamine (TMA) containing species like carnitine are metabolized to TMA by the gut microbiota.…”

Section: Pro-inflammatory Metabolitesmentioning

confidence: 99%

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

Coras

Murillo-Saich

Gumá

2020

Cells

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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved the treatment of RA, patients often inquire about dietary interventions to improve RA symptoms, as they perceive pain and/or swelling after the consumption or avoidance of certain foods. There is evidence that some foods have pro- or anti-inflammatory effects mediated by diet-related metabolites. In addition, recent literature has shown a link between diet-related metabolites and microbiome changes, since the gut microbiome is involved in the metabolism of some dietary ingredients. But diet and the gut microbiome are not the only factors linked to circulating pro- and anti-inflammatory metabolites. Other factors including smoking, associated comorbidities, and therapeutic drugs might also modify the circulating metabolomic profile and play a role in RA pathogenesis. This article summarizes what is known about circulating pro- and anti-inflammatory metabolites in RA. It also emphasizes factors that might be involved in their circulating concentrations and diet-related metabolites with a beneficial effect in RA.

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“…Also, by CT heart scanning, we cannot disclose the calcified plaques Betaine is a nutrient that acts as osmolyte and methyl group donor to maintain organ function [83]. Low plasma levels of betaine associate with cardiovascular events [84]. While the direct vascular effect of betaine remains to be explored [85,86], an indirect protective role on vascular health could be speculated given To compare RLS with traditional statistical methods, we performed univariate Spearman's rank correlation and multivariate logistic regression.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic features of vascular calcification in chronic kidney disease

et al. 2019

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Background Patients with chronic kidney disease stage 5 (CKD5) are predisposed to vascular calcification (VC), but the combined effect of factors associated with VC was sparsely investigated. We applied the relaxed linear separability (RLS) feature selection model to identify features that concomitantly associate with VC in CKD5 patients. Methods Epigastric arteries collected during surgery from living donor kidney transplant recipients were examined to score the histological extent of medial VC. Sixty‐two phenotypic features in 152 patients were entered into RLS model to differentiate between no–minimal VC (n = 93; score 0‐1) and moderate–extensive VC (n = 59; score 2‐3). The subset of features associated with VC was selected on the basis of cross‐validation procedure. The strength of association of the selected features with VC was expressed by the absolute value of ‘RLS factor’. Results Among 62 features, a subset of 17 features provided optimal prediction of VC with 89% of patients correctly classified into their groups. The 17 features included traditional risk factors (diabetes, age, cholesterol, BMI and male sex) and markers of bone metabolism, endothelial function, metabolites, serum antibodies and mitochondrial‐derived peptide. Positive RLS factors range from 1.26 to 4.05 indicating features associated with increased risk of VC, and negative RLS factors range from −0.95 to −1.83 indicating features associated with reduced risk of VC. Conclusion The RLS model identified 17 features including novel biomarkers and traditional risk factors that together concomitantly associated with medial VC. These results may inform further investigations of factors promoting VC in CKD5 patients.

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Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study

Cited by 108 publications

References 46 publications

Circulating metabolites from the choline pathway and acute coronary syndromes in a Chinese case-control study

Circulating metabolites from the choline pathway and acute coronary syndromes in a Chinese case-control study

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

Phenotypic features of vascular calcification in chronic kidney disease

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