Ambient air pollution associated with incidence and progression trajectory of cardiometabolic diseases: A multi-state analysis of a prospective cohort

Previous studies on the association between ambient air pollution and cardiometabolic diseases (CMDs) focused on a single disease, without considering cardiometabolic multimorbidity (CMM) and the progression trajectory of CMDs.Based on the UK Biobank cohort, we included 372,530 participants aged 37-73 years at baseline (2006-2010) with follow-up until September 2021. Incident CMDs cases were identified based on self-reported information and multiple health-related records in the UK Biobank. CMM was defined as the occurrence of at least two CMDs, including ischemic heart disease (IHD), stroke and type 2 diabetes (T2D). Exposure to ambient air pollutants, including particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM2.5), ≤10 μm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated at participants' geocoded residential addresses based on the high-resolution (1 × 1 km) pollution data from 2001 to 2021 provided by UK Department for Environment, Food and Rural Affairs. Multi-state models with adjustment for potential confounders were used to examine the impact of long-term exposure to ambient air pollution on transitions from healthy to first CMD (FCMD), subsequently to CMM, and further to death.During a median follow-up of 12.6 years, 40,112 participants developed at least one CMD, 3896 developed CMM, and 21,739 died. Among the four pollutants, PM2.5 showed the strongest associations with all transitions from healthy to FCMD, to CMM, and then to death [hazard ratios (95 % confidence intervals) per interquartile range (IQR) increment: 1.62 (1.60, 1.64) and 1.68 (1.61, 1.76) for transitions from healthy to FCMD and from FCMD to CMM, and 1.62 (1.59, 1.66), 1.67 (1.61, 1.73), and 1.52 (1.38, 1.67) for death risk from healthy, FCMD, and CMM, respectively]. After dividing FCMDs into three specific CMDs, we found that ambient air pollution had differential impacts on disease-specific transitions within the same transition phase.Our findings indicate that there is potential for air pollution mitigation in contributing to the prevention of the development and progression of CMDs.