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ORIGINAL RESEARCH article

Front. Physiol.

Sec. Metabolic Physiology

Volume 16 - 2025 | doi: 10.3389/fphys.2025.1677194

Comprehensive Analysis of Risk Factors and Metabolic Profiling in Preclinical Atherosclerosis: A Cross-Sectional Study

Provisionally accepted
Li  LiuLi Liu1*Fengrong  WangFengrong Wang2Lijie  JiangLijie Jiang1Tiehong  LiuTiehong Liu1Linlin  DongLinlin Dong1Tianjiao  ZhangTianjiao Zhang1Guoling  HuGuoling Hu1
  • 1Affiliated Zhongshan Hospital of Dalian University, Dalian, China
  • 2Liaoning University of Traditional Chinese Medicine Affiliated Hospital, Shenyang, China

The final, formatted version of the article will be published soon.

Aim: This study aimed to explore the factors influencing preclinical atherosclerosis (PCA) and provide evidence-based recommendations for its prevention. Non-targeted metabolomics technology was utilized to identify potential metabolic biomarkers associated with PCA. Materials and Methods: Data on general conditions, risk factors, and metabolic biochemical test results were collected from both the PCA group patients and the control group people. Blood plasma metabolites were analyzed using LC-MS/MS, which is a powerful technique that couples the separation power of liquid chromatography (LC) with the highly sensitive and specific detection of tandem mass spectrometry (MS/MS), making it indispensable for the comprehensive and accurate metabolic profiling required in preclinical atherosclerosis studies. Metabolites were annotated using the HMDB and LIPIDMaps databases, and differential metabolite pathways were enriched using the KEGG database. Results: Significant differences were observed between the two groups in terms of BMI, diet habits, smoking, physical activity, hypertension, and diabetes. Multivariate analysis identified smoking, high-salt diet, hypertension, and diabetes as significant risk factors for PCA. Biochemical blood tests revealed significantly elevated levels of TG, LDL-C, GLU, and UA in the PCA group compared to the control group. Metabolomic analysis identified 2 105 differential metabolites in positive ion mode (29 up-regulated and 76 down-regulated) and 105 differential metabolites in negative ion mode (39 up-regulated and 66 down-regulated). The primary metabolic differences between the groups were related to lipid metabolism, inflammation-mediated processes, and amino acid metabolism. Conclusion: The incidence of PCA is influenced by smoking, unhealthy diet habits, hypertension, and diabetes. PCA patients frequently exhibit abnormalities in lipid metabolism, glucose metabolism, and purine metabolism. Metabolomic studies indicate that the metabolic differences in PCA primarily involve lipid metabolism, energy metabolism, and amino acid metabolism.

Keywords: preclinical, Atherosclerosis, Risk factors, Metabolomics, Mass Spectrometry

Received: 31 Jul 2025; Accepted: 20 Oct 2025.

Copyright: © 2025 Liu, Wang, Jiang, Liu, Dong, Zhang and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Li Liu, frtolily@126.com

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