Dissecting the connection between volatile organic compounds and cardiovascular disease: immune cell-mediated mechanism

BACKGROUND: Volatile organic compounds (VOCs) are increasingly recognized as environmental pollutants with detrimental effects on human health. However, their specific effect on cardiovascular disease remains insufficiently explored. OBJECTIVE: This study aims to investigate the association between urinary VOC metabolites and cardiovascular disease risk, while evaluating whether monocytes may partially explain. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were analyzed. Three statistical models were employed to evaluate the association between VOC metabolites and cardiovascular disease risk. Mediation analysis was used to quantify the contribution of monocytes. Transcriptomic analysis and pathway enrichment were conducted to identify biological pathways linked to VOC exposure and immune dysregulation. RESULTS: All three models consistently demonstrated significant positive associations between urinary DHBMA, HPMMA, and ATCA and the risk of angina and coronary heart disease. Stratified analyses identified several high-risk subgroups-normal-weight adults (BMI <25 kg/m²), moderately active individuals (3-6), both low-income (PIR ≤1) and high-income (PIR >3) populations, and current drinkers-who exhibited the strongest VOC-CVD relationships. Mediation analysis showed that monocyte-related pathways accounted for 13.1 %-112.4 % of these associations. Finally, transcriptomic profiling revealed significant enrichment of NF-κB and AGE-RAGE signaling pathways, underscoring their roles in VOC-induced inflammation and immune dysregulation. CONCLUSION: Our study shows that higher levels of urinary DHBMA, HPMMA, and ATCA are associated with increased cardiovascular risk through monocyte-driven inflammation. Importantly, normal-weight and moderately active adults, socioeconomically vulnerable groups, and drinkers emerge as high-risk subpopulations. These findings suggest the need for targeted public health interventions, such as improving indoor air quality, reducing VOC emissions, and addressing monocyte-mediated inflammation, to reduce VOC-related cardiovascular risks.