Associations of Urinary Isoprostanes with Structural and Load-Dependent Arterial Stiffness — The Multi-Ethnic Study of Atherosclerosis

Total carotid pulse wave velocity (T-PWV), a measure of arterial stiffness, is caused by structural (S) remodeling and elevated blood pressure exerting a pressure-load on the arterial wall. Isoprostanes are oxidative stress biomarkers that have been associated with arterial stiffness. We sought to investigate the cross-sectional and longitudinal associations of urinary 8-isoprostane (iPF2α-III) and its metabolite (iPF2α-III-M), measured at a single timepoint at baseline, with carotid T-PWV, S-PWV, and load-dependent (LD)-PWV in a subset (n=744) of participants enrolled in the Multi-Ethnic Study of Atherosclerosis. We hypothesized that higher iPF2α-III and iPF2α-III-M concentrations would be associated with higher T-PWV, S-PWV, and LD-PWV. These relationships were evaluated using multivariable linear regression models adjusted for potential confounders in the entire analytical sample and in analyses stratified by hypertension medication class and race/ethnicity. In cross-sectional analyses of the entire analytic sample, there were no associations of acute iPF2α-III or iPF2α-III-M with carotid T-PWV, S-PWV, or LD-PWV after adjusting for risk factors. In adults taking angiotensin-II acting anti-hypertensive medications, higher iPF2α-III was associated with higher S-PWV, while higher iPF2α-III-M was associated with higher T-PWV and S-PWV. In the entire analytic sample, baseline isoprostanes were not associated with carotid PWV measured nearly a decade later. However, in analyses stratified by race/ethnicity higher baseline iPF2α-III was associated with higher S-PWV nearly a decade later among self-identified White participants. These results suggest that single timepoint measures of urinary 8-isoprostane are not a robust biomarker of arterial stiffness but may be associated with structural remodeling in select populations.