Long-term air pollution, cardiometabolic multimorbidity, and genetic susceptibility: a multi-state modeling study of 415,855 participants

BackgroundCardiometabolic multimorbidity (CMM) with at least two cardiometabolic diseases (CMDs) including type II diabetes (T2D), ischemic heart disease (IHD), and stroke, is a global health problem with multiplicative mortality risk and deserves to be investigated as a top priority. Although air pollution is a leading modifiable environmental risk for individual CMD, its impacts on CMM progression were poorly understood. ObjectiveTo elucidate the impact of air pollution on CMM progression, individually and in the context of genetic preposition. DesignMulti-state modeling cohort study. SettingData were extracted from the UK Biobank. Participants415,855 eligible UK Biobank adults that were free of CMDs at baseline. MeasurementsAnnual concentrations of particulate matter (PM) with a diameter of [≤]2.5 m (PM2.5), 2.5-10 m (PM2.5-10), and [≤]10 m (PM10), and nitrogen oxides (NOx and NO2) were estimated using Land Use Regression model. ResultsDuring a median follow-up of 8.93 years, 33,375 participants had a first CMD (FCMD), and 3,257 subsequently developed CMM. PM2.5, PM10, NO2, and NOx levels, as well as their combined exposure were associated with increased FCMD risks and even higher risks of CMM. Particularly, per a 5-g/m3 increase in PM2.5, risks for FCMD and CMM increased by 27% (95% confidence interval: 20%-34%) and 41% (18%-68%), respectively. By FCMD types, participants with IHD had a higher risk of CMM than those with T2D or stroke. Eighty-five CMD-related genetic variants were associated with CMM trajectories in our study and associations of air pollution with FCMD and CMM risks could be aggravated progressively with increasing genetic risks. LimitationsOther major air pollutants including ozone and SO2 were not considered due to the data availability. ConclusionsAir pollution has profound adverse health impacts on the progression of CMM through multi-stage dynamics, especially for individuals with IHD and high genetic risk.