# Metabolic Signatures of Air Pollution and Major Adverse Cardiovascular Events in Patients Undergoing Cardiac Catheterization

## TL;DR

This study finds that air pollution is linked to specific metabolic changes that increase the risk of major cardiovascular events in patients.

## Contribution

The study identifies specific metabolites that mediate the cardiovascular risks associated with air pollutants like CO and NOx.

## Key findings

- Higher CO exposure was associated with a 24% increased risk of major adverse cardiovascular events.
- 1-oleoyl-rac-glycerol was linked to all pollutants and cardiovascular outcomes like myocardial infarction and stroke.
- NOx's effect on cardiovascular events was partially mediated by choline.

## Abstract

Air pollution is an environmental risk factor for coronary artery disease. The molecular mechanisms linking fine particulate matter (PM2.5), nitrogen oxide (NOx), and carbon monoxide (CO) to coronary artery disease prognosis remains unclear.

The objective of the study was to investigate the molecular pathways linking air pollution to cardiovascular risk by analyzing the metabolome, focusing on the mediating role of metabolites.

We analyzed data from the Emory Cardiovascular Biobank, including 244 participants with metabolomic profiling, air pollution data, and a median follow-up of 9.8 (IQR: 4.6-12.2) years. Metabolomic profiling was performed via liquid chromatography-high- resolution mass spectrometry, and pollutants (PM2.5, NOx, CO) were estimated based on residence. Linear regression assessed pollutant-metabolite associations, adjusting for demographics and clinical factors. Competing risk models examined major adverse cardiovascular events (MACE), and Cox models evaluated all-cause mortality. Pathway and mediation analyses explored pollution-related metabolites.

Per IQR higher in CO was associated with a 24% higher risk in MACE (subdistribution HR [sHR]: 1.24; 95% CI: 1.03-1.49; P = 0.02), whereas PM2.5 (sHR: 1.05; 95% CI: 0.86-1.30; P = 0.62) and NOx (sHR: 1.19; 95% CI: 0.99-1.44; P = 0.068) suggested a modest but not significant elevated risk. Both NOx and CO demonstrated associations with cardiovascular mortality, whereas NOx was associated with congestive heart failure. 1-oleoyl-rac-glycerol was associated with all pollutants and linked to myocardial infarction and stroke. Mediation analysis showed NOx’s effect on MACE was mediated by choline.

Air pollution links to metabolic changes that contribute to cardiovascular disease progression and MACE.