Paper Information

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.

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.

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.