Long-term exposure to the general external exposome and incidence of ischemic heart disease in Europe: a meta-analysis of 14 cohorts

Background The relationship between the general external exposome and cardiovascular health remains underexplored. We evaluated the association between long-term exposure to the general external exposome and ischemic heart disease (IHD) incidence across Europe. Methods We followed IHD incidence in eight adult traditional cohorts, and six administrative cohorts from 11 European countries. We estimated aspects of the general external exposome at residential addresses, including an air pollution domain (PM 2·5 , PM 10 , NO 2 ), and a built-environment domain (greenspace and blue space, impervious surface, walkability, urbanization). We used time-varying exposures Cox proportional hazard models to evaluate single associations and quantile g-computation models to evaluate joint associations between the general external exposome and IHD incidence. We performed random effects meta-analyses by cohort types. Findings More than 29 million participants were followed of whom 464,386 developed IHD. In adult cohorts, single associations for air pollution and lack of MSAVI were positive but not statistically significant. In administrative cohorts, one-quartile increment in PM 2 · 5 , PM 10 , NO 2 , lack of MSAVI, distance to greenspace, and impervious surface were associated with 1·4% (95% CI 0·8%–1·9%), 0·9% (0·1%–1·7%), 1·7% (1·0%–2·4%), 1·9% (1·2%–2·7%), 0·3% (0·0%–0·6%), and 1·1% (0·6%–1·5%) higher IHD incidence, respectively. In joint-exposure analyses, air pollution, built environment, and combined domains showed comparable positive associations in both cohort types, but these were statistically significant only in administrative cohorts. One-quartile increment in air pollution, built environment and combined domains was associated with 2·5% (1·9%; 3·1%), 2·9% (1·6%; 4·3%), and 3·8% (2·8%; 4·7%) higher IHD incidence in administrative cohorts, respectively. Air pollution, greenspace, and impervious surface accounted for the largest share of these joint associations. Interpretation Higher levels of the general external exposome, individually and jointly, were associated with increased IHD incidence in administrative cohorts, supporting multi-exposure urban planning. Funding This study is supported by the European Union's Horizon 2020 research and innovation programme (No 874627), Formas (2022-00468) and Ulla Hamberg Angeby and Lennart Angeby Foundation 2022 (2022-02870).