Nationwide potential causal long-term effects of PM2.5 component mixture on ischemic heart disease mortality in the United States, 2000–2019

Background Ischemic heart disease (IHD) is a leading cause of global mortality. Although fine particulate matter (PM 2.5 ) is a risk factor, the nationwide causal contributions of its chemical components and their mixture to IHD mortality remain unclear. Methods We conducted a nationwide study covering 3108 counties across the contiguous United States during 2000–2019. Using a difference-in-differences design with two-way fixed models, we estimated long-term potential causal effects of individual PM 2.5 components on IHD mortality and applied quantile g-computation to quantify the joint mixture effects and the weights of each component. We further evaluated the effect modification by demographic characteristics, socioeconomic factors, and seasonal temperatures. Results An interquartile-range increase in 5 PM 2.5 components was associated with 1.61–8.83% increases in IHD mortality. The component mixture was associated with a 0.92% (95% CI: 0.60, 1.25) increase in IHD mortality, with sulfate (weight: 43.69%) and nitrate (34.97%) contributing the largest positive weights. The association was greater among older adults (effect increase: 4.81%), Hispanic or Latino (3.83%), and in counties with higher poverty (0.30%), higher physical inactivity (0.92%), and warmer climates (0.33–0.51%). Conversely, Black or African American (effect decrease: 2.46%) and higher health insurance coverage (1.05%) appeared to attenuate this association. Conclusions This study provides potential causal links for the joint effects of PM 2.5 component mixtures on IHD mortality, with stronger associations among vulnerable subpopulations, and identifies sulfate and nitrate as critical components. These findings underscore the necessity of emission controls targeting toxic constituents alongside public health strategies designed to protect susceptible populations.