Impact of ambient ozone exposure on cardiac biomarkers in heart failure and the role of Sodium-glucose cotransporter-2 inhibitors: Findings from the TRACER-HF trial

Aims: This study aimed to evaluate the impact of ambient ozone (O₃) exposure on changes in cardiac biomarkers in heart failure patients, identify vulnerable populations, and explore potential effect modification by concomitant medications. Methods: A repeated measures analysis was employed to evaluate the association between O₃ exposure and cardiac biomarkers, including 1038 N-terminal pro-brain natriuretic peptide (NT-proBNP), 692 soluble growth stimulation expressed gene 2 (sST2), and Troponin T measurements from 173 heart failure patients enrolled in the TRACER-HF trial across 10 cities in China. Linear mixed models were applied to assess the exposure-response relationships across multiple lag periods. Results: The study shows that O₃ exposure was significantly associated with increased Troponin T across multiple lag periods. Troponin T increased by 3.23 % (95 % CI: 1.57, 4.93) at lag 0–7 days per 10 μg/m³ O₃ increase, whereas sST2 and NT-proBNP slightly decreased. Notably, Sodium-glucose Cotransporter-2 inhibitors (SGLT2i) significantly modified the adverse effect of O₃ across all examined periods. For lag 0–7 days, O₃ exposure was associated with increased Troponin T by 4.12 % in non-SGLT2i users and 2.12 % in SGLT2i users (P = 0.046). Conclusion: This study shows that ambient O₃ exposure was associated with an increase in Troponin T levels, which may indicate myocyte injury. Additionally, this study identified the significant modification effect of SGLT2i in exploratory analysis, providing a hypothesis for a potential strategy to mitigate O₃ related cardiac injury. Further studies are needed to confirm these findings and evaluate their clinical applicability.