Urinary biomarkers of oxidative and nitrosative stress and the risk for incident stroke: A nested case-control study from a community-based cohort

BackgroundOxidative and nitrosative stress has suggested to be involved in the pathophysiology of cardiovascular diseases, but has unclear relationship with the risk for incident stroke.MethodsIn this nested case-control study, cases consisted of 131 participants who were free of stroke at screening and experienced incident stroke during the follow-up period. Controls were 1:1 frequency-matched for age and sex. Baseline levels of urinary creatinine-indexed biomarkers were measured using liquid chromatography-tandem mass spectrometry, including 8-iso-prostaglandin F2α (8-iso-PGF2α), 4-hydroxynonenal conjugate with mercapturic acid, 8-hydroxydeoxyguanosine and 8-nitroguanine.ResultsThe levels of urinary 8-iso-PGF2α in stroke cases were higher than in controls [median (interquartile range), 1.13 (2.23-4.36) μg/g creatinine versus 0.71 (1.34-3.02) μg/g creatinine, p = 0.004]. After adjusting cardiovascular risk factors, the association remained that higher level of urinary 8-iso-PGF2α entailed the greater risk for incident stroke [per 1 standard deviation increase in log-transformed value, adjusted odds ratio, 1.40; 95% confidence interval (CI), 1.06-1.85; p = 0.005] with a significant increasing trend across its quartiles (p for trend = 0.016). After adding urinary 8-iso-PGF2α, the prediction model not only improved discrimination between participants with or without incident stroke (integrated discrimination improvement, 0.025; 95% CI, 0.006-0.045; p = 0.005), but enhanced stroke risk stratification (net reclassification improvement, 19.8%; 95% CI, 4.6-35.1%; p = 0.011). In contrast, the relationships were non-significant among the other three biomarkers.ConclusionsOur findings demonstrated that urinary 8-iso-PGF2α could be an independent biomarker of oxidative stress for prediction of the risk for incident stroke.