Aging-Related Decline of Glutathione Peroxidase 3 and Risk of Cardiovascular Events in Patients With Atrial Fibrillation

Background: experimental studies demonstrated that glutathione peroxidase 3 (gpx3),an antioxidant enzyme that catabolizes hydrogen peroxide,protects against thrombosis. little is known about its role in cardiovascular disease. methods and results: a prospective cohort study was conducted in 909 atrial fibrillation patients. serum activities of gpx3,superoxide dismutase (sod),and catalase were measured at baseline to assess the risk of cardiovascular events during a mean follow-up of 43.4 months (3291 person-years). serum nox2 and urinary excretion of 11-deydro-thromboxane b2 were also measured. during follow-up 160 cardiovascular events occurred (4.9%/year). significantly lower values of gpx3 (p<0.001) and sod (p=0.037) were detected in patients with,compared to those without,cardiovascular events. a lower survival rate was observed in patients with gpx3 (p<0.001) and sod (p=0.010) activities below the median,as compared to those above. in a fully adjusted cox regression model,gpx3 was the only antioxidant enzyme predictor of cardiovascular events (hazard ratio 0.647,95% confidence interval 0.524-0.798,p<0.001). gpx3 was inversely associated with urinary 11-dehydro-thromboxane b2 (b -0.337,p<0.001) and serum nox2 (b: -0.423,p<0.001). gpx3 activity progressively decreased with decades of age (p<0.001),with a progressive reduction in people aged ≥70 years. conclusions: this study provides evidence that a low antioxidant status,as depicted by reduced levels of gpx3,increases the risk of cardiovascular events in patients with atrial fibrillation. the age-related decline of gpx3 may represent a mechanism for the enhanced cardiovascular risk in the elderly population. © 2016 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.