# Impact of Food Exposome on Atherosclerotic Plaque Stability: Metabolomic Insights from Human Carotid Endarterectomy Specimen

## TL;DR

This study uses metabolomics to show that plant-based diets, including coffee, may stabilize carotid plaques, while excessive niacin from processed foods could increase risk.

## Contribution

The study provides novel metabolomic evidence linking food exposome markers to carotid plaque stability.

## Key findings

- Caffeine metabolites like paraxanthine and methylxanthine are associated with plaque stability and higher HDL-cholesterol.
- Plant-based diet biomarkers such as N5-acetylornithine and gentisic acid correlate with stable plaques.
- N-methylpyridone carboxamides, linked to niacin excess, are associated with plaque vulnerability and higher CRP.

## Abstract

Carotid atherosclerotic stenosis (CAS) is a leading cause of ischemic stroke. Current understanding of plaque vulnerability remains largely confined to histopathological characterization. Consequently, identifying molecular determinants of plaque stability represents a major challenge to advance prevention strategies. Untargeted metabolomic analysis was performed using mass spectrometry coupled to liquid chromatography on carotid plaques removed from patients with CAS undergoing endarterectomy. To identify factors influencing plaque stability, we compared 42 asymptomatic with 30 symptomatic CAS patients. Associations between each annotated metabolite in plaques and asymptomatic CAS status were assessed using logistic regression models. Asymptomatic patients exhibited lower plasmatic levels of C-reactive protein (CRP) and higher HDL-cholesterol. Within the plaques, caffeine and its catabolites, paraxanthine and methylxanthine, were associated with plaque stability and were correlated with HDL-cholesterol. Additional plant-based diet biomarkers including N5-acetylornithine, gentisic acid, proline betaine, and homostachydrine were also associated with plaque stability. In contrast, N-methylpyridone carboxamides, reflecting niacin excess, involved in vascular inflammatory processes, were both associated with plaque vulnerability and also correlated with higher CRP. Our findings provide molecular evidence that plant-based diets, including coffee, promote carotid plaque stability, while excessive niacin intake, linked to processed foods, may be detrimental. Metabolomics offers new insights into food exposome-related vascular risk.