Interactive effects of short-term ozone exposure and plasma biomarkers related to nitric oxide pathway and inflammation on myocardial ischemia

Background: No study has explored the possible interactive effects of short-term ozone (O₃) exposure and plasma endothelial and inflammatory biomarkers, including cyclic guanosine monophosphate (cGMP), nitric oxide metabolite (NO_x), myeloperoxidase (MPO), and high-sensitive C-reactive protein (hs-CRP), on myocardial ischemia, indicated by ST-segment depression events (STDE) recorded in ambulatory electrocardiograms. Methods: A L-arginine (L-Arg) intervention study with 118 participants was carried out using a standardized 24-h exposure protocol, employing a multivariable linear regression model to assess the effects of O₃ exposure on plasma biomarkers, and a generalized linear model to investigate the effects on 24-hour STDE. The possible interactive effects of short-term O₃ exposure and plasma biomarkers on indicators of myocardial ischemia were also investigated by including product interaction terms between ambient O₃ and plasma biomarkers in the models. We also explored whether L-Arg supplementation could alleviate the adverse effects of ambient O₃ exposure. Results: Data from 107 participants were included in final analysis. Short-term O₃ exposure was associated with significantly decreased plasma cGMP and MPO levels, and increased 24-h STDE risk, with plasma cGMP and MPO modifying the O₃-STDE associations. Participants with lower plasma levels of cGMP or higher MPO demonstrated increased vulnerability to the harmful effects of ambient O₃ on 24-h STDE in inferior leads. L-Arg supplementation attenuated the effects of short-term O₃ exposure on plasma MPO and hs-CRP. Conclusions: Plasma biomarkers (cGMP and MPO) are likely involved in the potential pathways connecting ambient O₃ exposure and harmful cardiac effects. Supplementation with L-Arg showed the potential to mitigate the inverse effects of ambient O₃ exposure on inflammation.