Long-term exposure to ambient air pollution and incident cardiovascular disease in adults with cardiovascular-kidney-metabolic stages 0-3: a nationwide prospective cohort study in China.

Cardiovascular-Kidney-Metabolic (CKM) stages 0-3 represent a key window for cardiovascular disease (CVD) prevention, yet the effects of long-term ambient air pollution in this population remain unclear. In this longitudinal analysis of a nationwide prospective cohort, we analyzed 6,321 adults without baseline CVD from the China Health and Retirement Longitudinal Study (CHARLS). Long-term exposure to PM2.5, NO2, and warm-season O3 was estimated using the China High Air Pollutants satellite-based dataset, which provides pollutant surfaces at 1-km resolution (10-km for NO₂). Incident CVD through 2018 was physician-diagnosed. Cox models were used to evaluate baseline and time-varying associations, and non-linear and joint effects were examined using spline and multipollutant approaches. During a median follow-up of 6.9 years, 896 participants developed CVD. Each 10 µg/m³ increase in baseline PM2.5 or NO2 was associated with a 20% higher CVD risk (PM2.5: HR 1.20, 95% CI 1.13-1.28; NO2: HR 1.20, 1.07-1.35). Time-varying models confirmed these findings and additionally identified a significant association with O3 (HR = 1.20, 95% CI: 1.11-1.30). Restricted cubic spline analyses indicated non-linear exposure-response relationships, with thresholds of 39.64 µg/m3 for PM2.5 and 39.86 µg/m3 for NO2. Multipollutant models showed a positive mixture effect dominated by PM2.5, and stronger associations were observed in participants from eastern China (P interaction < 0.01). Long-term exposure to PM2.5, NO2, and O3 increases CVD risk in adults with CKM stages 0-3, with PM2.5 as the leading driver. These findings highlight the need to incorporate air pollution into CKM-based cardiovascular prevention strategies.