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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Air pollution; Catecholamines; Monoamines; Sympathetic nervous system; Volatile organic compounds.