ArticleClinical chemistry2021
Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study.
Article in Clinical chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 5 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Gut microbiota-derived trimethylamine N-oxide and the incidence and recurrence of atrial fibrillation: a systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2026Pooled it
- Gut microbiome and atrial fibrillation: mechanistic insights metabolites and comorbidities. Systematic review.Gut microbes · 2025Pooled it
- Association of gut microbiome dysbiosis with the progression of atrial fibrillation: A systematic review.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2023Pooled it
- The heart and gut relationship: a systematic review of the evaluation of the microbiome and trimethylamine-N-oxide (TMAO) in heart failure.Heart failure reviews · 2022Pooled it
- Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies.Nutrients · 2022Pooled it
- Marked Changes in One-Carbon Metabolism on a Low-Carbohydrate High-Fat Diet: A Randomized Controlled Trial (CARBFUNC).The Journal of nutrition · 2026Trial
- Trimethylamine N-oxide and major adverse cardiac and cerebrovascular events: results of umbrella review and meta-analysis.Nutrition & metabolism · 2026Article
- Multi-Omics Genome-Wide to Explore the Formation and Development Targets for Intracranial Aneurysms.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Choline status and related health outcomes in humans: A scoping review.Nutrition and health · 2026Article
- Metabolic Signatures of Atrial Functional Impairment in Paroxysmal Atrial Fibrillation Patients: A CMR Strain-metabolomics Study.Journal of cardiovascular translational research · 2026Article
- The Mediterranean diet and cardiovascular disease.Cardiovascular research · 2025Review
- Dysregulation of the FGF21-Adiponectin Axis in a Large Cohort of Patients with Severe Obesity and Liver Disease.International journal of molecular sciences · 2025Article
- Urea, TMAO, betaine and other osmolytes as endogenous diuretics in heart failure and hypertension.Heart failure reviews · 2025Review
- Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health.Metabolites · 2025Review
- High-throughput untargeted metabolomic profiling of urinary biomarkers in acute myocarditis patients: a cross-sectional study.Scientific reports · 2025Article
- Recent advances in precision nutrition and cardiometabolic diseases.Revista espanola de cardiologia (English ed.) · 2025Review
- Systematic Mendelian Randomization Exploring Druggable Genes for Hemorrhagic Strokes.Molecular neurobiology · 2025Article
- Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure.JACC. Advances · 2025Article
- Pre-procedural TMAO as a predictor for recurrence of atrial fibrillation after catheter ablation.BMC cardiovascular disorders · 2024Observational
- Microbiome-Derived Trimethylamine N-Oxide (TMAO) as a Multifaceted Biomarker in Cardiovascular Disease: Challenges and Opportunities.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 2 countries.
Funding
Abstract
backgroundFew studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations.
methodsProspective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models.
resultsAfter adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30-2.63) and 1.57 (1.09-2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99-1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03-1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57-4.03), 1.65 (1.00-2.71) and 1.65 (1.04-2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF.
conclusionsOur findings support the role of the choline metabolic pathway in the pathogenesis of AF and HF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.