Abstract
BACKGROUND: Long-term exposure to PM2.5 and low physical activity are independently associated with an increased risk of cardiovascular disease (CVD). However, there is limited research investigating the combined effects of PM2.5 exposure and physical activity on CVD risk. This study aims to explore these interactions related to CVD and mortality. METHODS: We analysed data from the PURE-China cohort, including 39,970 adults aged 35-70 years, with a median follow-up of 11.9 years. PM2.5 exposure was estimated using a Bayesian hierarchical model. Physical activity was quantified using metabolic equivalent task (MET)-minutes per week. The primary outcome was a composite of all-cause mortality and major cardiovascular events. Cox frailty models and restricted cubic splines were used to assess associations. Interaction effects were evaluated using measures of multiplicative and additive interaction, including the relative excess risk due to interaction (RERI) and the proportion attributable to interaction (AP). FINDINGS: Participants were divided into high and low PM2.5 exposure groups by the median concentration (47.70 μg/m(3)). In low-exposure areas, higher total physical activity significantly reduced the risk of composite outcome (HR: 0.84, 95% CI: 0.73-0.97, p trend = 0.012) and major cardiovascular events (HR: 0.80, 0.67-0.95, p trend = 0.022). However, in high-exposure regions, physical activity showed no protective effect for the composite outcome (HR: 0.97, 0.85-1.09, p trend = 0.551) and major cardiovascular events (HR: 0.98, 0.85-1.13, p trend = 0.864). Higher non-recreational physical activity reduced the risks of composite outcome and major CVD in low-exposure areas but provided no benefit in high-exposure regions (p interaction = 0.011, 0.024, respectively). Significant antagonistic interaction was observed between high PM2.5 exposure and low non-recreational physical activity for the composite outcome (RERI: -0.215, 95% CI: -0.406 to -0.024; AP: -0.155, 95% CI: -0.294 to -0.017). INTERPRETATION: Long-term exposure to high PM2.5 concentrations diminishes the cardiovascular benefits of physical activity, particularly non-recreational activities. These findings underscore the need for tailored physical activity guidelines and air quality interventions in heavily polluted regions to maximize public health benefits. FUNDING: Funding sources are listed at the end of the Article.