# Comprehensive analysis of risk factors and metabolic profiling in preclinical atherosclerosis: a cross-sectional study

## TL;DR

This study identifies risk factors and metabolic changes linked to early atherosclerosis, offering insights for prevention and early detection.

## Contribution

The study provides a comprehensive metabolomic profile of preclinical atherosclerosis and identifies key risk factors and metabolic pathways.

## Key findings

- Smoking, high-salt diet, hypertension, and diabetes are significant risk factors for preclinical atherosclerosis.
- PCA patients show elevated triglycerides, LDL-C, glucose, and uric acid levels compared to controls.
- Metabolomic analysis reveals lipid, inflammation, and amino acid metabolism as key pathways affected in PCA.

## Abstract

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.

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.

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 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.

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.