Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure

Background: Little is known about the associations between choline metabolites (total choline, phosphatidylcholine, and glycine) and the incidence of heart failure (HF). Objectives: The purpose of this study was to assess the associations of choline metabolites with incident HF and examine the effec...

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Main Authors: Jie Li, MS, Jiang Li, PhD, Ying Sun, PhD, Yanqi Fu, MS, Xiao Tan, PhD, Ningjian Wang, MD, PhD, Yingli Lu, MD, PhD, Bin Wang, MD, PhD
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:JACC: Advances
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772963X24007257
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author Jie Li, MS
Jiang Li, PhD
Ying Sun, PhD
Yanqi Fu, MS
Xiao Tan, PhD
Ningjian Wang, MD, PhD
Yingli Lu, MD, PhD
Bin Wang, MD, PhD
author_facet Jie Li, MS
Jiang Li, PhD
Ying Sun, PhD
Yanqi Fu, MS
Xiao Tan, PhD
Ningjian Wang, MD, PhD
Yingli Lu, MD, PhD
Bin Wang, MD, PhD
author_sort Jie Li, MS
collection DOAJ
description Background: Little is known about the associations between choline metabolites (total choline, phosphatidylcholine, and glycine) and the incidence of heart failure (HF). Objectives: The purpose of this study was to assess the associations of choline metabolites with incident HF and examine the effect modification by genetic susceptibility. Methods: This prospective cohort study followed 245,072 participants from the UK Biobank from baseline (2006-2010) until March 30, 2023. Participants were free of cardiovascular diseases at baseline. Circulating choline metabolites were quantitated using nuclear magnetic resonance spectrometer. Cox proportional hazards models were fitted to assess the association of choline metabolites and genetics with incident HF. Two-sample Mendelian randomization analyses were implemented to confirm the findings in observational analysis. Results: During a median follow-up of 14.1 years, 5,468 incident HF cases were documented. Total choline and phosphatidylcholine were positively associated with HF risk (HR: 1.08 [95% CI: 1.04-1.12] and HR: 1.08 [95% CI: 1.05-1.12], per one SD increase, respectively). Compared with the lowest quartile group, the HR for the highest quartile group was 1.23 (95% CI: 1.12-1.35) for total choline and 1.23 (95% CI: 1.12-1.34) for phosphatidylcholine. Glycine was inversely associated with HF risk (HR: 0.97 [95% CI: 0.94-0.99], per one SD increase). Participants with high polygenic risk score and high total choline or phosphatidylcholine had the highest risk of HF, whereas participants with low polygenic risk score and high glycine had the lowest risk. No statistically significant interactions were observed between choline metabolites and genetic susceptibility to HF. The Mendelian randomization analysis supported the potential causal associations of total choline (OR: 1.71 [95% CI: 1.01-1.35]) and glycine (OR: 0.93 [95% CI: 0.88-0.99]) with HF. Conclusions: Circulating choline metabolites were associated with the risk of incident HF, independent of genetic susceptibility. Whether targeting the metabolic pathway of choline might be a potential strategy for improving heart health warrants further validation.
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spelling doaj-art-1fb68ceff76842f4963283d6d18f45f52024-12-16T05:39:10ZengElsevierJACC: Advances2772-963X2025-01-0141101445Choline Metabolites, Genetic Susceptibility, and Incident Heart FailureJie Li, MS0Jiang Li, PhD1Ying Sun, PhD2Yanqi Fu, MS3Xiao Tan, PhD4Ningjian Wang, MD, PhD5Yingli Lu, MD, PhD6Bin Wang, MD, PhD7Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Big Data in Health Science, School of Public Health, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Address for correspondence: Dr Yingli Lu, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Dr Bin Wang, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.Background: Little is known about the associations between choline metabolites (total choline, phosphatidylcholine, and glycine) and the incidence of heart failure (HF). Objectives: The purpose of this study was to assess the associations of choline metabolites with incident HF and examine the effect modification by genetic susceptibility. Methods: This prospective cohort study followed 245,072 participants from the UK Biobank from baseline (2006-2010) until March 30, 2023. Participants were free of cardiovascular diseases at baseline. Circulating choline metabolites were quantitated using nuclear magnetic resonance spectrometer. Cox proportional hazards models were fitted to assess the association of choline metabolites and genetics with incident HF. Two-sample Mendelian randomization analyses were implemented to confirm the findings in observational analysis. Results: During a median follow-up of 14.1 years, 5,468 incident HF cases were documented. Total choline and phosphatidylcholine were positively associated with HF risk (HR: 1.08 [95% CI: 1.04-1.12] and HR: 1.08 [95% CI: 1.05-1.12], per one SD increase, respectively). Compared with the lowest quartile group, the HR for the highest quartile group was 1.23 (95% CI: 1.12-1.35) for total choline and 1.23 (95% CI: 1.12-1.34) for phosphatidylcholine. Glycine was inversely associated with HF risk (HR: 0.97 [95% CI: 0.94-0.99], per one SD increase). Participants with high polygenic risk score and high total choline or phosphatidylcholine had the highest risk of HF, whereas participants with low polygenic risk score and high glycine had the lowest risk. No statistically significant interactions were observed between choline metabolites and genetic susceptibility to HF. The Mendelian randomization analysis supported the potential causal associations of total choline (OR: 1.71 [95% CI: 1.01-1.35]) and glycine (OR: 0.93 [95% CI: 0.88-0.99]) with HF. Conclusions: Circulating choline metabolites were associated with the risk of incident HF, independent of genetic susceptibility. Whether targeting the metabolic pathway of choline might be a potential strategy for improving heart health warrants further validation.http://www.sciencedirect.com/science/article/pii/S2772963X24007257choline metabolismgenetic riskheart failureMendelian randomizationprospective cohort
spellingShingle Jie Li, MS
Jiang Li, PhD
Ying Sun, PhD
Yanqi Fu, MS
Xiao Tan, PhD
Ningjian Wang, MD, PhD
Yingli Lu, MD, PhD
Bin Wang, MD, PhD
Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure
JACC: Advances
choline metabolism
genetic risk
heart failure
Mendelian randomization
prospective cohort
title Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure
title_full Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure
title_fullStr Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure
title_full_unstemmed Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure
title_short Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure
title_sort choline metabolites genetic susceptibility and incident heart failure
topic choline metabolism
genetic risk
heart failure
Mendelian randomization
prospective cohort
url http://www.sciencedirect.com/science/article/pii/S2772963X24007257
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