Air pollution, lifestyle, and cardiovascular disease risk in northwestern China: A cohort study of over 5.8 million participants

• Limited evidence links air pollution-lifestyle interplay to cardiovascular disease. • Study includes over 5.8 million participants from arid Northwestern China. • Air pollution in dust-prone areas is linked to cardiovascular disease. • Exercise is crucial in reducing the risk of cardiovascular disease from air pollution. • Air pollution and unhealthy lifestyles jointly heighten cardiovascular risk. Evidence on the combined impact of air pollution and lifestyle on cardiovascular disease (CVD) risk is limited. We employed the Space-Time Extra-Trees model, an ensemble learning method for spatiotemporal data, to estimate the annual average concentrations of five air pollutants from 2017 to 2019. Cox proportional hazards models were used to assess the associations between air pollutant exposure and CVD incidence. A lifestyle score, based on body mass index, waist circumference, diet, physical activity, alcohol consumption, and smoking, was developed to examine the moderating effect of lifestyle on the air pollution-CVD relationship. Among 5,838,833 baseline participants without CVD, 414,218 developed CVD during follow-up. Long-term exposure to particulate matter (PM 1 , PM 2.5 , PM 10 ), ozone (O 3 ), and carbon monoxide (CO) was significantly associated with increased CVD risk. Stratified analyses revealed that exercise had the most significant impact on this association, with exercisers showing a notable reduction in risk compared to non-exercisers. An interaction between air pollution and lifestyle was observed (P-interaction < 0.001). Compared to individuals with a relatively healthy lifestyle and low air pollution exposure, those with an unhealthy lifestyle and high exposure had the highest risk of developing CVD (PM 1 : HR = 1.660, PM 2.5 : HR = 1.891, PM 10 : HR = 1.755, O 3 : HR = 1.970, CO: HR = 1.426). Further analysis revealed a synergistic additive interaction between lifestyle and air pollution, leading to relative excess risks of 0.151, 0.154, 0.137, 0.171, and 0.095 in groups with relatively unhealthy lifestyles and high exposure to PM 1 , PM 2.5 , PM 10 , O 3 , and CO, respectively. Thus, in addition to controlling major air pollutant emissions, promoting healthy lifestyle adoption is crucial.