Key result
Elevated circulating choline is linked to a ~33% higher incidence of heart failure.
Why the study?
The relationship between circulating choline metabolites and heart failure development and adverse outcomes, as well as the underlying mechanisms, was not fully evaluated.
Are elevated circulating levels of choline and its metabolites associated with an increased risk of heart failure development and adverse clinical outcomes?
Meta-Analysis (n=267,569)
Are elevated circulating levels of choline and its metabolites associated with an increased risk of heart failure development and adverse clinical outcomes?
Elevated circulating levels of choline and phosphatidylcholine are associated with an increased risk of developing heart failure, highlighting potential novel therapeutic targets.
May link choline metabolites to HF risk; hypothesis-generating and requires prospective trials before practice change.
BACKGROUND: The objectives of this systematic review and meta-analysis were to (i) evaluate the relationship between circulating levels choline and its metabolites, phosphatidylcholine (PC), trimethylamine N-oxide (TMAO), betaine, and dimethylglycine (DMG) with heart failure (HF) development and its adverse clinical outcomes (ii) explore potential mechanisms that link them to HF. METHODS: A systematic search of MEDLINE, EMBASE, and PubMed was conducted. RESULTS: Nine prospective cohort studies (n = 267,569) were analysed. Elevated choline and PC were significantly associated with an increased incidence of HF respectively HR 1.33 (95 % CI 1.07-1.66, p = 0.0107) and HR 1.25 (95 % CI 1.16-1.34, p < 0.0001). In established HF, elevated betaine levels were significantly associated with a composite of adverse clinical outcomes (HR 1.15, 95 % CI 1.02-1.30, p = 0.0206). The molecular mechanisms linking choline and PC to HF include the hydrolysis of PC into lysophosphatidylcholine which can produce inflammation and cardiomyocyte apoptosis. Several metabolites and pathways are intriguing therapeutic targets, including lysophosphatidylcholine acyltransferase 1, phospholipase A2, choline trimethylamine lyase, and the phosphatidylethanolamine N-methyltransferase pathway. CONCLUSIONS: Choline metabolites are implicated in HF development and progression. Understanding the mechanism whereby choline metabolism leads to HF may lead to novel therapeutic targets for HF management and prevention.
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Shokravi et al. (2025) conducted a meta-analysis in Heart failure (n=267,569). Elevated circulating choline was evaluated on Incidence of heart failure (HR 1.33, 95% CI 1.07-1.66, p=0.0107). Elevated circulating choline was significantly associated with an increased incidence of heart failure (HR 1.33; 95% CI 1.07-1.66; p=0.0107).
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