Long-term ambient air pollution is not associated with circulating soluble urokinase plasminogen activator receptor

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a stable chronic-inflammation biomarker causally implicated in atherosclerosis, yet its modifiable determinants remain largely uncharacterized. Long-term ambient air pollution is an established cardiovascular risk factor and a biologically plausible determinant of suPAR. METHODS: In this cross-sectional analysis, we tested associations of long-term residential air pollution with circulating suPAR in 5,072 participants of the Multi-Ethnic Study of Atherosclerosis, drawn from six US metropolitan regions and enrolled during 2000-2002. Residential exposures were estimated with the validated Multi-Ethnic Study of Atherosclerosis Air spatiotemporal model, and serum suPAR was measured by enzyme-linked immunosorbent assay. RESULTS: In multivariable linear regression adjusted for demographic, socioeconomic, and cardiovascular risk factors, neither fine particulate matter, nitrogen dioxide, nitrogen oxides, ozone, nor light-absorbing carbon was associated with suPAR; the fine particulate matter confidence interval excluded effect sizes of two percent or greater per 5 µg/m³. CONCLUSIONS: Together with two prior cohorts spanning two continents and three age ranges, these findings indicate that long-term ambient air pollution is unlikely to be a meaningful determinant of circulating suPAR or a major mediator of the air-pollution-cardiovascular-disease association, and suggest that the search for modifiable determinants of this clinically actionable biomarker should focus elsewhere.