Prediction of myocardial infarction, stroke and cardiovascular mortality with urinary biomarkers of oxidative stress: Results from a large cohort study.

BACKGROUND: Oxidative stress contributes to endothelial dysfunction and is involved in the pathogenesis of cardiovascular diseases (CVD). However, large population-based cohort studies are sparse and biomarkers of oxidative stress have not been evaluated for CVD risk prediction so far. METHODS: The associations of urinary oxidized guanine/guanosine (OxGua) levels (including 8-hydroxy-2'-deoxyguanosine (8-OHdGuo)) and 8-isoprostane levels with myocardial infarction, stroke and CVD mortality were examined in a population-based cohort of 9949 older adults from Germany with 14 years of follow-up in multivariable adjusted Cox proportional hazards models. RESULTS: Both OxGua and 8-isoprostane levels were associated with CVD mortality independently from other risk factors (hazard ratio (HR) [95% confidence interval] of top vs. bottom tertile: 1.32 [1.06; 1.64] and 1.58 [1.27; 1.98], respectively). Moreover, CVD mortality risk prediction was significantly improved when adding the two biomarkers to the European Society of Cardiology's Systematic Coronary Risk Evaluation (ESC SCORE) tool. The area under the curve (AUC) increased from 0.739 to 0.752 (p = 0.001). In addition, OxGua levels were associated with stroke incidence (HR for 1 standard deviation increase: 1.07 [1.01; 1.13]) and 8-isoprostane levels were associated with fatal stroke incidence (HR of top vs. bottom tertile: 1.77 [1.09; 2.89]). With respect to myocardial infarction, associations were observed for both biomarkers in obese subjects (BMI ≥ 30 kg/m2). CONCLUSIONS: These results from a large cohort study add evidence to the involvement of an imbalanced redox system to the etiology of CVD. In addition, 8-isoprostane and OxGua measurements were shown to be useful for an improved CVD mortality prediction.