Long-term air pollution exposure and cardiovascular disease progression in rheumatoid arthritis: A prospective cohort study using multi-state model analysis

Abstract

Background

Patients with rheumatoid arthritis (RA) have a significantly elevated risk of developing cardiovascular disease (CVD), the leading cause of their death. However, the impact of environmental factors on RA progression remains unclear. This study aimed to explore the link between long-term air pollution exposure and the multi-stage progression from a healthy status to RA onset, then CVD development, and finally death.

Methods

Utilizing data from 326,059 participants in the UK Biobank, we used a unidirectional multi-state Markov proportional hazards model to analyze the associations between long-term exposure to air pollutants (PM_2.5, PM₁₀, NO₂, and NO_x) and disease progression. The models included transitions from baseline healthy state to RA onset, to subsequent CVD, and to death. Air pollution exposure was assessed using land use regression models, and hazard ratios (HRs) were calculated per interquartile range (IQR) increase in pollutant concentrations.

Results

During a median follow-up of 12.69 years, 3422 participants developed RA, of whom 424 subsequently developed CVD. PM_2.5 and NO₂ showed the most extensive effects across transition stages. Per IQR increase in PM_2.5 was associated with increased risks of RA onset (HR: 1.08; 95 %CI: 1.03, 1.12) and RA to death (HR: 1.20; 95 %CI: 1.06, 1.37), while NO₂ was associated with increased risks of RA onset (HR: 1.10; 95 %CI: 1.06, 1.15) and subsequent CVD development (HR: 1.13; 95 %CI: 1.01, 1.28). Notably, valve disorders showed associations with multiple pollutants, and these effects were more pronounced in women and elderly participants.

Conclusion

Long-term exposure to air pollutants was significantly associated with increased risks at multiple transition stages, from RA onset to subsequent CVD development and death, although effect sizes were modest for some transitions. Considering the widespread global exposure to air pollution, these findings emphasize the importance of air pollution control in preventing RA and its cardiovascular complications, especially among susceptible populations.