Associations of residential outdoor air pollution with incident cardiovascular disease: a nationwide cohort study of 1.8 million adults in Wales

Background Cardiovascular diseases (CVD) remain a major public health burden. Growing evidence links outdoor air pollution to CVD risk, but large-scale studies that integrate nationwide electronic health records (EHR) with household-level exposure estimates across several pollutants and across composite and CVD subtype outcomes remain limited. Purpose To quantify the association between residential outdoor air pollution and incident composite CVD and major CVD subtypes in a large, real-world primary care population. Methods We conducted a population-based cohort study using the Secure Anonymised Information Linkage (SAIL) Databank, including adults aged 18–84 years registered with general practices across Wales between 01/01/2004 and 31/12/2023. Separate cohorts for first-time composite CVD and then ischaemic heart disease (IHD), stroke, atrial fibrillation (AF), heart failure (HF), peripheral arterial disease (PAD) and valvular heart disease (VHD) were ascertained from linked primary care, hospital, mortality and demographic service records, excluding those who had a recorded CVD or CVD subtype at cohort entry date. Modelled annual mean pollutant concentrations (UK government; 1x1km resolution) were linked to patient postcodes; exposure (PM2.5, PM10, NO2, NOX, SO2, O3) was defined as the annual mean in the year preceding cohort entry. We used cox proportional hazards models, adjusted for demographic, comorbidities, lifestyle factors and area-level deprivation, to quantify hazard ratios (HR) with 95% confidence intervals (95% CI) to explore associations between CVD and air pollutants (per SD increase in pollutant concentration). Results The full cohort comprises of 1,824,544 individuals (50.5% female; mean age: 42.3 years [SD:16.7]), with a median follow-up time of 12.2 years (IQR: 4.6-20.0). During follow-up 387,853 (21.3%) first-time CVD events were recorded. We found incidence rates varied across PM2.5 exposure deciles. Particularly for composite CVD (range: 11.32-20.31/1,000 PY), IHD (range: 6.14-13.12/1,000 PY) and stroke (range: 3.36-6.62/1,000 PY) (Figure 1). We observed associations between several CVDs and air pollutants. Notably, IHD and PM2.5 (HR: 1.18; 95% CI: 1.18-1.19), PM10 (HR: 1.15; 95% CI: 1.14-1.15), and O3 (HR: 1.18; 95% CI: 1.17-1.19), and composite CVD and PM2.5 (HR: 1.10; 95% CI: 1.10-1.11) and O3 (HR: 1.11; 95% CI: 1.11-1.12) (Figure 2). Conclusion In a nationwide EHR-linked cohort with postcode-level exposure assignment, higher residential air pollutant concentrations were associated with increased incidence of composite CVD and several CVD subtypes. Having initially explored associations, we now aim to incorporate air pollutants as time-dependent exposures and use inverse probability of treatment weighting on the cohorts to estimate the marginal (population-average) effects.