• Jian Xiong, Ying Liao, Liyuan Yang, Ying Wei, Dehua Li, Yi Zhao, Qianhua Zheng, Wenchuan Qi, and Fanrong Liang.
• College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.
• Postgrad Med J. 2024 Jun 4.

PurposeWe aimed to explore the causal relationship between human serum metabolites and angina pectoris.MethodsThis study used two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and angina pectoris. The analytical methods employed to reduce study bias included inverse variance weighted, MR-Egger, and weighted median method. A comprehensive sensitivity analysis was performed using the leave-one-out method, while instrumental variable pleiotropy was tested with MR-Pleiotropy RESidual Sum and Outlier. Metabolic pathways of angina-associated metabolites were analysed on the MetaboAnalyst metabolomics analysis tool platform.ResultsIn this study, 42 serum metabolites were found to be strongly associated with angina pectoris. They mainly belonged to seven groups: amino acids, carbohydrates, cofactors and vitamins, lipids, nucleotides, unknown metabolites, and exogenous substances. Pipecolate posed the highest risk for the development of angina pectoris among the 42 serum metabolites. The main metabolic pathways associated with angina pectoris were glycine, serine, threonine metabolism, primary bile acid biosynthesis, and caffeine metabolism.ConclusionWe identified 25 high-risk and 17 protective human serum metabolites associated with angina pectoris. Their associated major metabolic pathways were also determined. The serum metabolite pipecolate was significantly and positively correlated with the risk of angina pectoris. This finding may serve as a valuable reference for testing serum markers associated with angina pectoris.© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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