AUTHOR=Liu Li , Wang Fengrong , Jiang Lijie , Liu Tiehong , Dong Linlin , Zhang Tianjiao , Hu Guoling TITLE=Comprehensive analysis of risk factors and metabolic profiling in preclinical atherosclerosis: a cross-sectional study JOURNAL=Frontiers in Physiology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1677194 DOI=10.3389/fphys.2025.1677194 ISSN=1664-042X ABSTRACT=AimThis 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 MethodsData 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.ResultsSignificant 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 triglycerides, LDL-C, GLU, and UA in the PCA group compared to the control group. Metabolomic analysis identified 105 differential metabolites in positive ion mode (29 upregulated and 76 downregulated) and 105 differential metabolites in negative ion mode (39 upregulated and 66 downregulated). The primary metabolic differences between the groups were related to lipid metabolism, inflammation-mediated processes, and amino acid metabolism.ConclusionThe 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.