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BACKGROUND: The associations between air pollution exposure and morbidity and mortality of cardiovascular diseases (CVDs) have been widely reported; however, evidence on such associations across different dynamic disease trajectories remain unknown. OBJECTIVE: We examined whether ambient air pollution during the prehypertension (pre-HTN) stage could aggravate the progression from hypertension (HTN) to CVD, and consequent death. METHODS: A total of 168,010 adults with pre-HTN (120-139 mmHg systolic blood pressure or 80-89 mmHg diastolic blood pressure) from the UK Biobank were included in this analysis. We used a multistate model to explore the associations between five air pollutants (PM2.5, PM2.5 absorbance, PM10, NO2, and NOx) and the risk of six disease transitions (from pre-HTN to HTN, from pre-HTN to CVD, from pre-HTN to death, from HTN to CVD, from HTN to death, and from CVD to death). Mediation analyses were further conducted to explore the role of intermediate diseases in the dynamic progression of CVDs. RESULTS: During a median follow-up of 12 y, 13,743 (8.18%) of participants with pre-HTN developed HTN, whereas 12,825 (7.63%) and 4,467 (2.66%) directly developed CVD or died, respectively. Air pollution was positively associated with the dynamic disease progression. For example, a per-interquartile range increase of PM2.5 was significantly associated with the hazard ratios (HRs) of 1.105 [95% confidence intervals (CI): 1.083, 1.127], 1.045 (95% CI: 1.022, 1.068), and 1.086 (95% CI: 1.047, 1.126) in the transition from pre-HTN to HTN, CVD, and death, respectively. Higher levels of air pollution were associated with increased transition probability of disease progression. Mediation analyses indicated that intermediate diseases subsequently significantly mediated air pollutant-associated risk to develop more serious disease. CONCLUSIONS: This study provides evidence that air pollution might play a role in the early stages of CVD progression. Controlling air pollution might be an effective measure to prevent CVD progression and reduce the disease burden of CVD. [ABSTRACT FROM AUTHOR]