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Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure
1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
JACC. Advances
|January 10, 2025
Summary
Higher levels of total choline and phosphatidylcholine are linked to increased heart failure (HF) risk, while glycine shows a protective association. These choline metabolites are associated with HF risk, independent of genetic factors.
Area of Science:
- Cardiovascular Medicine
- Metabolomics
- Genetics
Background:
- The relationship between choline metabolites (total choline, phosphatidylcholine, glycine) and heart failure (HF) incidence is not well understood.
- Investigating these associations is crucial for identifying novel risk factors and potential therapeutic targets for HF.
Purpose of the Study:
- To assess the associations between circulating choline metabolites and incident heart failure (HF).
- To examine whether genetic susceptibility modifies the relationship between choline metabolites and HF risk.
Main Methods:
- A prospective cohort study of 245,072 UK Biobank participants (2006-2010 to 2023), free of cardiovascular disease at baseline.
- Quantification of choline metabolites using nuclear magnetic resonance and analysis of incident HF risk using Cox proportional hazards models.
- Mendelian randomization analyses were employed to investigate potential causal relationships.
Main Results:
- Over 14.1 years, 5,468 incident HF cases were identified. Total choline and phosphatidylcholine showed a positive association with HF risk (HR: 1.08 per SD increase).
- Glycine demonstrated an inverse association with HF risk (HR: 0.97 per SD increase).
- Mendelian randomization supported potential causal links for total choline and glycine with HF.
Conclusions:
- Circulating choline metabolites are associated with incident HF risk, independently of genetic predisposition.
- Targeting choline metabolism pathways may represent a future strategy for heart health improvement, requiring further validation.
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