Long-term exposure to ultrafine particles and incidence of cardiovascular and cerebrovascular disease in the EPIC-NL cohort

Abstract

Background: There is a small but growing evidence base that exposure to ultrafine particles (UFP – particles smaller than 100nm) may play an important role in the etiology of several illnesses, including cardiovascular disease (CVD). However, this has been under-explored in population-level studies. Methods: Using Cox proportional hazard models we studied the association between long-term exposure to UFP (predicted via recently developed land use regression models) and incident cardiovascular disease in the Dutch arm of the European Prospective Investigation into Cancer cohort (EPIC-NL), which contains 33,831 Dutch residents. Hazard ratios (HR) for UFP were compared to HRs for more routinely monitored air pollutants, including PM$_{10}$, PM$_{coarse}$, PM$_{2.5}$, PM$_{2.5}$ absorbance, NO$_{x}$, and NO$_{2}$. Joint-pollutant effects were also evaluated in two-pollutant models. Results: Long-term exposure to UFP was associated with increased HRs for all incident cardiovascular disease (HR = 1.18 per 10,000 particles/cm$_{3}$, 95% CI: 1.03, 1.34), myocardial infarction (HR = 1.34, 95% CI: 1.00, 1.79), and heart failure (HR = 1.76, 95% CI: 1.17, 2.66). Positive associations were also observed for NO2 (HR for heart failure = 1.22, 95% CI: 1.01, 1.48 per 20 μg/m$^{3}$) and coarse PM (HR for all CVD = 1.21, 95% CI: 1.01, 1.45 per 10 μg/m$^{3}$). CVD was not positively associated with PM$_{2.5}$ (HR for all CVD = 0.95, 95% CI: 0.75, 1.28 per 5 μg/m$^{3}$). HRs for UFP and cerebrovascular diseases were positive, but not significant. In two-pollutant models (UFP + NO$_{2}$ and UFP + PM$_{coarse}$), positive associations tended to remain for UFP, while HRs for PM$_{coarse}$ and NO$_{2}$ generally attenuated towards the null. Conclusions: These findings strengthen the overall evidence that UFP exposure plays an important role in cardiovascular health and that risks of ambient air pollution, based on conventional air pollution metrics, may underestimate the true population risk.ment data and biological responses as viability (AlamarBlue assay), cytotoxicity (LDH release), and release of cytokines during long-term exposure are reported