Association of Ozone and Temperature with Ischemic Heart Disease Mortality Risk: Mediation and Interaction Analyses

Global warming and elevated ozone (O 3 ) levels are gradually gaining widespread attention, and exposure to which may cause many physiological changes associated with cardiovascular events such as hypertension, cardiomyocyte apoptosis, etc. In addition, ischemic heart disease (IHD) is the leading cause of death worldwide. However, the contributions of temperature and O 3, independently or in combination, to IHD mortality are not well understood. This study employs a two-stage analytical protocol (generalized additive model followed by meta-analysis) to explore the respective associations of temperature and O 3 with IHD mortality, and determine their possible mediation and interaction effects. Our results suggest that increases of 10 μg/m 3 in O 3 and 1 °C in temperature at lag01 day are associated with increased IHD mortality risks of 0.789% and 0.686%, respectively. O 3 can mediate the relationship between temperature and IHD mortality, with a pooled estimate of 0.140%, while temperature can mediate the association between O 3 and IHD mortality, with a pooled estimate of 0.162%. The additive and multiplicative interaction effects of O 3 and temperature were significantly associated with IHD mortality. The study findings demonstrate that higher temperature and O 3 concentrations can increase human IHD mortality risk through interaction and mediation effects, providing a scientific basis for the synergistic management of temperature and O 3 or associated interventions.