Li Jie, Li Jiang, Sun Ying, Fu Yanqi, Tan Xiao, Wang Ningjian, Lu Yingli, Wang Bin
Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
JACC Adv. 2024 Dec 14;4(1):101445. doi: 10.1016/j.jacadv.2024.101445. eCollection 2025 Jan.
Little is known about the associations between choline metabolites (total choline, phosphatidylcholine, and glycine) and the incidence of heart failure (HF).
The purpose of this study was to assess the associations of choline metabolites with incident HF and examine the effect modification by genetic susceptibility.
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.
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.
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.
关于胆碱代谢物（总胆碱、磷脂酰胆碱和甘氨酸）与心力衰竭（HF）发病率之间的关联，人们了解甚少。
本研究旨在评估胆碱代谢物与新发HF的关联，并研究遗传易感性的效应修饰作用。
这项前瞻性队列研究对英国生物银行的245,072名参与者进行了从基线（2006 - 2010年）至2023年3月30日的随访。参与者在基线时无心血管疾病。使用核磁共振光谱仪对循环胆碱代谢物进行定量分析。采用Cox比例风险模型评估胆碱代谢物和遗传学与新发HF的关联。实施两样本孟德尔随机化分析以证实观察性分析中的结果。
在中位随访14.1年期间，记录到5468例新发HF病例。总胆碱和磷脂酰胆碱与HF风险呈正相关（每增加一个标准差，风险比[HR]分别为1.08[95%置信区间（CI）：1.04 - 1.12]和1.08[95%CI：1.05 - 1.12]）。与最低四分位数组相比，总胆碱最高四分位数组的HR为1.23（95%CI：1.12 - 1.35），磷脂酰胆碱最高四分位数组的HR为1.23（95%CI：1.12 - 1.34）。甘氨酸与HF风险呈负相关（每增加一个标准差，HR为0.97[95%CI：0.94 - 0.99]）。多基因风险评分高且总胆碱或磷脂酰胆碱水平高的参与者发生HF的风险最高，而多基因风险评分低且甘氨酸水平高的参与者风险最低。未观察到胆碱代谢物与HF遗传易感性之间存在统计学显著的相互作用。孟德尔随机化分析支持总胆碱（比值比[OR]：1.71[95%CI：1.01 - 1.35]）和甘氨酸（OR：0.93[95%CI：0.88 - 0.99]）与HF之间的潜在因果关联。
循环胆碱代谢物与新发HF风险相关，独立于遗传易感性。靶向胆碱代谢途径是否可能是改善心脏健康的潜在策略，有待进一步验证。
