Unraveling the choline pathway in heart failure risk and outcomes: A systematic review and meta-analysis

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.

A systematic search of MEDLINE, EMBASE, and PubMed was conducted.

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.

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.