Exposure to volatile organic compounds - acrolein, 1,3-butadiene, and crotonaldehyde - is associated with vascular dysfunction.

Abstract Background Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Exposure to air pollution, specifically particulate matter of diameter ≤2.5 μm (PM2.5), is a well-established risk factor for CVD. However, the contribution of gaseous pollutant exposure to CVD risk is less clear. Objective To examine the vascular effects of exposure to individual volatile organic compounds (VOCs) and mixtures of VOCs. Methods We measured urinary metabolites of acrolein (CEMA and 3HPMA), 1,3-butadiene (DHBMA and MHBMA3), and crotonaldehyde (HPMMA) in 346 nonsmokers with varying levels of CVD risk. On the day of enrollment, we measured blood pressure (BP), reactive hyperemia index (RHI – a measure of endothelial function), and urinary levels of catecholamines and their metabolites. We used generalized linear models for evaluating the association between individual VOC metabolites and BP, RHI, and catecholamines, and we used Bayesian Kernel Machine Regression (BKMR) to assess exposure to VOC metabolite mixtures and BP. Results We found that the level of 3HPMA was positively associated with systolic BP (0.98 mmHg per interquartile range (IQR) of 3HPMA; CI: 0.06, 1.91; P=0.04). Stratified analysis revealed an increased association with systolic BP in Black participants despite lower levels of urinary 3HPMA. This association was independent of PM2.5 exposure and BP medications. BKMR analysis confirmed that 3HPMA was the major metabolite associated with higher BP in the presence of other metabolites. We found that 3HPMA and DHBMA were associated with decreased endothelial function. For each IQR of 3HPMA or DHBMA, there was a -4.4% (CI: -7.2, -0.0; P=0.03) and a -3.9% (CI: -9.4, -0.0; P=0.04) difference in RHI, respectively. Although in the entire cohort, the levels of several urinary VOC metabolites were weakly associated with urinary catecholamines and their metabolites, in Black participants, DHBMA levels showed strong associations with urinary norepinephrine and normetanephrine levels. Discussion Exposure to acrolein and 1,3-butadiene is associated with endothelial dysfunction and may contribute to elevated risk of hypertension in participants with increased sympathetic tone, particularly in Black individuals.