Air pollution as a mediator of heat-related all-cause mortality among older U.S. adults

Heatwaves increase mortality, particularly among the elderly. Fine particulate matter (PM 2.5 ) and ozone (O 3 ), have been proposed as a potential mediator linking extreme heat exposure to mortality, yet quantitative evidence remains limited. Here we quantify the mediating roles of PM 2.5 and O 3 in the relationship between heatwaves and all-cause mortality in the United States. We conducted a national daily analysis of Medicare beneficiaries aged ≥ 65 across 15,692 ZIP codes during June-September from 2000 to 2016. Heatwaves were defined as ≥ 3 consecutive days exceeding ZIP-specific 95th percentile of maximum temperature. Daily PM 2.5 and O 3 concentrations at 1-km resolution were estimated using ensemble machine learning models. We decomposed heatwave effects on mortality into natural direct effects and indirect effects mediated through each pollutant using causal mediation analysis and conducted stratified analyses by urbanicity using Rural–Urban Commuting Area (RUCA). mong 32.5 million ZIP code-days, we identified 5.3 million all-cause deaths and 3.2 million heatwave ZIP code-days (10% of all ZIP code-days). Heatwaves increased mortality risk by 1.9% (RR = 1.019, 95% CI: 1.015–1.024) and are associated with elevated PM 2.5 (averaged 5.45 μg/m 3 increase) and O 3 (averaged 11.30 ppb increase). PM 2.5 mediated 17.80% (95% CI 12.09–24.27) of heatwave mortality, while O 3 mediated 8.19% (95% CI 2.15–14.03). Mediation effects were only observed in urban areas (PM 2.5 : ∼19%; O 3 : ∼9%), with no detectable mediation in suburban/rural settings despite significant pollution increases. Our findings demonstrate that air pollution, especially PM 2.5 , mediates the heatwave effects on all-cause mortality among older adults in urban settings. Air quality control may be a feasible strategy for mitigating heat-related mortality.