Abstract Introduction Exposure to air pollution (AP) is a modifiable risk factor for cardiovascular diseases. Aim To analyse the short-term effects of AP on the occurrence of acute coronary syndromes (ACS). Methods The EP-PARTICLES study consists of a retrospective nationwide cohort of Eastern Poland residents (N= 8,077,671). The area is characterized by a specific type of pollution - Polish smog, featuring high concentrations of particulate matter (PM), benzo(a)pyrenes (BaP) and favourable atmospheric conditions of formation. Medical data were collected from the National Health Fund and the Central Statistical Office. The records included sex and age and the causes of hospitalization. The analysis utilized air quality modeling data from the GEM-AQ system, which allowed to provide daily pollution concentration at the level of each LAU (ie. local administrative units, at municipality level), throughout the observation period. We estimated LAU specific associations of AP concentration using quasi-Poisson generalized additive models. We controlled our models for long-term trends and weather conditions. In the second stage, we pooled LAU-specific estimates with a random-effects meta-analysis. The results are presented as % risk ratio (RR), and 95% confidence intervals (95% CIs) for the two-day moving average of AP concentration on the present day and the day after exposure (ie. LAG0-1). Cluster analysis was performed on LAU levels from 19 variables using the k-mens clustering using the Ward minimum variance method. The set of variables included demographic, ecological, socioeconomic, environmental conditions. Results Over the years 2011-20, we noted 2,141,213 hospitalizations due to CVD, including 139,697 ACS cases (45.2% STEMI). The main triggers for ACS were PM2.5 (RRLAG0-1 1.04 95%CI 1.028-1.053), BaP (RRLAG0-1 1.021 95%CI 1.01-1.032). We identified three distinct clusters: Cluster 1 was characterized by high population density and GPD per capita and highest prevalence of atrial fibrillation. Cluster 2 (40% of the entire population) exhibited significantly high variability, characterized by low population density and GPD per capita, the highest prevalence of heart failure, people drinking alcohol and smoking tobacco. Cluster 3 (7% of the entire population) was in the middle but showed the highest prevalence of hypertension, diabetes and renal failure. Cluster 2 inhabited areas with low concentrations of PMs and BaP and demonstrated increased vulnerability to the effects of PM2.5 and BaP from 3% to 5.2% (P<0.001). For details see Figure 1. Conclusions PM and BaP are important factors associated with the occurrence of MACE. AP exposure should be considered in CVD prevention models. Cluster classification helps in risk stratification and prognosis. Adverse effects of AP can be mitigated by attention to improving socio-economic status and hazardous habits.Associations between AP exposure and ACS