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

Abstract

Introduction Oxidative stress contributes to endothelial dysfunction and is involved in the pathogenesis of cardiovascular diseases (CVD). However, associations of biomarkers of oxidative stress with CVD have not yet been addressed in large cohort studies. Methods The associations of urinary 8-hydroxy-2’-deoxyguanosine (8-oxo-dG) and 8-isoprostane (8-iso) levels with total, fatal and non-fatal myocardial infarction (MI), total, fatal and non-fatal stroke and CVD mortality were examined in a population-based cohort of 9949 adults from Germany with 14 years of follow-up in multi-variable adjusted Cox proportional hazards models. Results Both 8-oxo-dG and 8-iso levels were associated with CVD mortality independently from other risk factors (hazard ratio [HR] [95% confidence interval (CI)] for top vs. bottom tertile: 1.31 [1.04–1.64] and 1.67 [1.33; 2.11], respectively). Moreover, CVD mortality risk prediction was significantly improved when adding both biomarkers to the Systematic Coronary Risk Evaluation (SCORE): area under the curve (AUC) increased from 0.735 to 0.749, P = 0.002. In addition, 8-oxo-dG levels were associated with total stroke incidence (HR for 1 standard deviation increase: 1.07 [1.01; 1.13]) and 8-iso levels were associated with fatal stroke incidence (HR for top vs. bottom tertile: 1.72 [1.04–2.85]). For MI, associations were only observed for 8-oxo-dG in subgroups defined by history of CVD or 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, urinary 8-oxo-dG and 8-iso level measurements were shown to be useful biomarkers for an improvement of CVD mortality prediction.