Volatile organic compounds and their relation to sympathetic activation and autonomic balance in humans.

Cardiovascular disease (CVD) is a multifaceted pathology that affects almost half of Americans ≥20 years old. One modifiable risk factor associated with CVD is air pollution exposure. The intricacy of air pollution exposure and CVD can make it difficult to elucidate on the multitude of mechanisms underpinning these associations. In this dissertation, we selected a relevant exposure (i.e., volatile organic compounds (VOC)) and an intermediate outcome (i.e., autonomic balance) that may represent one of these pertinent mechanisms. We tested the central hypothesis that higher VOC exposures would lead to increased sympathetic activation and autonomic imbalance. Aim 1 (Chapter III) utilized a large human cohort to assess the association between total VOC burden and individual VOC metabolites (VOCm) with monoamines, biomarkers of sympathetic activation. We found strong positive associations between 11 VOCm and monoamine metabolites, suggesting that VOC exposure may be linked to sympathetic activation. Furthermore, some of these associations appeared to be worse in females than males, indicating a sex-specific sensitivity to VOC exposure. Aim 2 (Chapter IV) expanded on Aim 1 by assessing associations in a smaller, 3-year longitudinal cohort measured at summer and winter timepoints. Results of Aim 2 were incongruent with Aim 1. We found negative associations between AAMA and multiple monoamine metabolites, whilst many other associations were non-significant. We did notice some VOCm showed seasonal differences, with more positive associations between VOCm and monoamines in summer months and more negative associations in winter months. Aim 3 (Chapter V) implemented an alternative outcome, heart rate variability (HRV), which is a proxy of autonomic balance. In this analysis we found contradicting positive associations between N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC), 2-Methylhippuric acid (2MHA), and 3-Methylhippuric acid + 4-Methylhippuric acid (3,4MHA) with HRV and negative associations between N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) and HRV. Season appeared to also influence Aim 3 results, demonstrating stronger positive associations between VOCm and HRV metrics during summer months compared to winter months. Collectively, this dissertation provides individual VOC-specific evidence for associations between VOC exposure, sympathetic activation and autonomic balance. Due to inconsistencies across aims (and cohorts), more research is needed to bolster evidence regarding VOC exposures and cardiac autonomic regulation.