Combined effects of heavy metals and volatile organic compounds on oxidative stress and cardiovascular risk.

Background: Oxidative stress contributes to early cardiovascular disease (CVD) but is rarely assessed clinically. Oxidative balance score (OBS) summarizes pro-/antioxidant factors, yet its relevance to CVD is understudied. Additionally, pollutants such as heavy metals (HMs) and volatile organic compounds (VOCs) raise oxidative stress but are often studied individually, limiting real-world applicability. The study aims to determine associations of HM + VOC exposures with OBS, and OBS with CVD. Methods: We analyzed NHANES 2011-2020 adults aged ≥20. Exposure to HMs + VOCs was determined via urine metabolites. OBS was calculated using 24-h dietary recall, physical activity, BMI, and serum cotinine. Associations between OBS and HM + VOC exposure were assessed using quantile g-computation and Bayesian Kernel Machine Regression, with subgroup analyses for age, sex, race/ethnicity, and monthly poverty level index. The relationship between OBS and CVD was determined via adjusted logistic regression, and mediation between OBS and CVD by various atherogenic indices was tested. Results: Among 6516 participants, higher OBS (lower oxidative stress) was associated with lower odds of CVD (OR = 0.969), with significant mediation via atherogenic indices. Combined HM + VOC exposure was significantly associated with reduced OBS (higher oxidative stress) with stronger associations among those who were female, aged 20-59, Mexican American, Non-Hispanic Asian, and with the highest income. Cadmium, Conclusion: HM + VOC mixture exposure was significantly associated with OBS, indicating increased oxidative stress as pollutant exposure increases. Higher OBS was significantly associated with lower odds of CVD. Future studies should investigate causal mechanisms underlying pollutants, OBS, and CVD.