Associations of sympathetic activation with exposure to volatile organic compounds: A cross-sectional study

Volatile organic compounds (VOCs) are ubiquitous gaseous chemicals emitted from multiple sources and present in both indoor and outdoor air. VOC exposures have been linked to detrimental cardiometabolic effects; nevertheless, the underlying mechanisms remain unclear. In this study, we evaluated the relationship between VOC exposure and sympathetic activation.

Participants (n=696, age 25-70 years) were recruited between 2018 and 2021 in Louisville, KY. Clean catch, spot urine samples were obtained. Urinary metabolites of VOCs and monoamines were quantified using UPLC-MS/MS. The associations of creatinine-adjusted, log-transformed urinary constituents were examined using adjusted multivariable linear regression models for individual metabolites and quantile-based g-computation for overall mixture models. Final models were adjusted for demographics, stress, smoking status, medication use, and urine collection time.

Higher urinary levels of several VOC metabolites were associated with higher urinary levels of monoamines and their metabolites. A quartile increase in the overall VOC metabolite mixture was associated with 27% [18%, 37%] (serotonin) to 54% [36%, 73%] (epinephrine) higher urinary parent monoamine concentrations. For phase I monoamine metabolites, concentrations were 25% [16%, 35%] (vanillylmandelic acid) to 37% [29%, 46%] (3-methoxytyramine) higher per quartile increase in VOC metabolite mixture.

Our results suggest that exposure to VOCs is associated with elevated sympathetic activation. Individual and mixture analyses identified robust associations with metabolites of N,N-dimethylformamide, 1,3-butadiene, ethylbenzene/styrene, propylene oxide, and crotonaldehyde. Elevated sympathetic tone may be a significant contributor to the negative cardiometabolic outcomes associated with VOC exposure.