ABSTRACT In this supplemental study, we propose to investigate the climate change effects on health, focusing specifically on the impact of wildland fire-enhanced air pollution on human health. The supplemental study will be built upon the ongoing SAPIA study, "Slowing Atherothrombosis Progression through Indoor Air Filtration," aiming to assess the effectiveness of HEPA filtration in reducing indoor PM2.5 exposure and the subsequent effects on improving atherothrombosis outcomes. The SAPIA study will enroll and follow up 52 participants aged 65-84 years old with ischemic heart disease history and living in the Los Angeles area in year 2023-2024. The aims of this supplemental study will extend the original SAPIA aims to focus on investigating adverse effects of wildfire exposures and assess the effectiveness of residential HEPA filtration in 1) reducing indoor exposure to PM2.5 during wildfire events and 2) alleviating the wildfire-induced adverse effects on acute cardiovascular outcomes (blood pressure, heart rate variability and biomarkers). We will use existing national and regional wildfire and air pollution monitoring networks to monitor wildfire events during the wildfire season (May-September). We will employ low-cost air quality sensors at participants' residential addresses to monitor indoor and outdoor PM2.5 levels. By using both time-series and dispersion models, we will validate the indoor and outdoor levels of wildfire- derived PM2.5 in both HEPA and non-HEPA settings. This approach will enable us to assess the effectiveness of HEPA filtration in reducing indoor PM2.5 concentrations. Once a wildfire event is identified, participants will be informed to complete questionnaires and collect urine and blood samples using pre-distributed and self-collection test kits. Daily blood pressure (BP) and heart rate variability will be remotely collected using Withings BP monitors and wearable Oura® rings. The advantages of this study include the use of a two-arm randomized trial nested within the ongoing SAPIA cross-over trial, wearable digital devices for real-time health monitoring, and self- collection of blood and urine samples, which enable the assessment of the acute health effects of wildfires. Findings of this study will help to assess the effectiveness of HEPA filtration as a preventive tool for the adverse health effects of wildfire-originated air pollution exposure. In conclusion, this supplemental study will contribute significantly to understanding the impact of climate change-enhanced wildfires on human health and the potential health benefits of HEPA filtration by reducing exposure to wildfire-originated PM2.5. By combining state-of-the- art exposure assessment methods, real-time health outcome monitoring and self-collection of biosamples, this study will provide valuable insights into the relationship between wildfire-originated air pollution and cardiovascular health, paving the way for future larger-scale studies in this field.