Associations of urinary polycyclic aromatic hydrocarbon metabolites and blood pressure with the mediating role of cytokines: A panel study among children

Little was known regarding the relations of polycyclic aromatic hydrocarbon (PAH) mixture with children's blood pressure (BP) and its potential mechanism. We conducted a panel study with up to 3 visits across 3 seasons in 2017-2018 among 103 children aged 4-13 years. Urinary PAH metabolites (OH-PAHs) were measured by gas chromatograph-tandem triple quadrupole mass spectrometer, and serum cytokines were detected by Bio-Rad 48-Plex Screening Panel. We employed linear mixed-effects models to assess the relations of each urinary OH-PAH with BP, least absolute shrinkage and selection operator (LASSO), and weighted quantile sum (WQS) regression to evaluate associations of OH-PAHs mixture with BP, and mediation analyses for the role of serum cytokines. We found the consistently positive associations of 1-hydroxynaphthalene and 9-hydroxyphenanthrene (9-OHPh) with systolic BP (SBP), 4-OHPh, and 9-OHPh with diastolic BP (DBP) and mean arterial pressure (MAP) in a dose-responsive manner. For instance, each 1-fold increment of 9-OHPh was related with increase of 0.92% (95% confidence interval (CI): 0.25%, 1.60%) in SBP, 1.32% (95%CI: 0.25%, 2.39%) in DBP, and 1.15% (95%CI: 0.40%, 1.88%) in MAP. Meanwhile, based on LASSO and WQS regression, OH-PAHs mixture was linked with increased DBP and MAP, to which 9-OHPh and 4-OHPh were the major contributors. Such relationships were modified by passive smoking status and 3-4 times stronger in passive smokers than non-passive smokers. A 1-fold increase in 9-OHPh was associated with an elevation of 3.51% in SBP among passive smokers while that of 0.55% in SBP among non-passive smokers. Furthermore, 4-OHPh and 9-OHPh were related to multiple cytokines elevation, of which platelet-derived growth factor (PDGF) mediated 9.99% and 12.57% in 4-OHPh-related DBP and MAP elevation, respectively. Accordingly, urinary OH-PAHs dominated by 9-OHPh and 4-OHPh were dose-responsively associated with elevated BP whereby a mechanism partly involving PDGF among children.

Automated summary

This study found a positive association between urinary polycyclic aromatic hydrocarbon (PAH) metabolites and children's blood pressure, with 9-hydroxyphenanthrene (9-OHPh) and 4-hydroxyphenanthrene (4-OHPh) as the major contributors. The relationship was modified by passive smoking status and stronger in passive smokers. The metabolites were also related to the elevation of multiple cytokines, with platelet-derived growth factor (PDGF) playing a role in the blood pressure elevation.