Assessing additive interactions of heat wave, fine particulate matter, and ozone on cardiovascular mortality in a typical cold region of China: A time-stratified case-crossover study.

Under the background of climate change, concurrent exposure to fine particulate matter (PM2.5), ozone (O3), and heat wave is becoming increasingly prevalent; however, their combined cardiovascular associations remain insufficiently characterized. We conducted a time-stratified case-crossover study including 499,996 cardiovascular disease (CVD) deaths during the warm season (May to September) in Heilongjiang Province, China, from 2013 to 2022. Conditional logistic regression models were applied to estimate short-term associations. Meteorological data and air pollutant concentrations were obtained from validated gridded datasets based on residential addresses. Under the P95_3d heat wave definition, the odds ratio (OR) of CVD mortality associated with heat wave-only exposure was 1.119 (95%CI: 1.103, 1.136). For heat wave-PM2.5 co-exposure, the relative excess odds due to interaction (REOI) was 0.048 (95%CI: 0.015, 0.080). For heat wave-O3 co-exposure, the REOI was 0.110 (95%CI: 0.078, 0.142). For heat wave-O3-PM2.5 triple co-exposure, the REOI was -0.023 (95%CI: -0.090, 0.044). Stratified analyses suggested higher co-exposure ORs among adults aged 65 years and older and females, although sex differences in additive interaction were not statistically significant. These findings suggest that compound exposure to heat wave and air pollution may be associated with an increased short-term CVD mortality burden in cold-region populations.