P776Prognostic significance of antioxidant enzymes in acute coronary syndromes.

PURPOSE: Antioxidant enzymes such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) constitute a defence against oxidative stress by scavenging key reactive oxygen species (ROS). In the context of acute coronary syndromes (ACS), the variance and prognostic significance of these enzymes is not clearly defined. Patients with low levels of GPx and SOD activity may have less capacity to scavenge ROS leading to an increased risk of Major Adverse Cardiovascular Events (MACE). This study aimed to test the hypothesis that patients with low levels of GPx and SOD activity would have a higher risk of MACE following an ACS.

METHODS: We prospectively enrolled ACS patients undergoing coronary angiography ± percutaneous coronary intervention. Clinical features and demographic data were recorded and blood samples collected prior to angiography. Plasma was assayed for GPx and SOD activity using colourimetric activity kits (Enzo LifeSciences). 1-year outcomes were collected, with a primary outcome measure of MACE, defined as a composite of death, myocardial infarction (MI), stroke (CVA), stent thrombosis and new heart failure (HF).

RESULTS: In 262 ACS patients (mean age 63 yrs, 69% male, 23% ST elevation MI, 71% non-ST elevation MI, 6% unstable angina) we observed considerable variation in the measures of GPx and SOD activity. The activity levels of these enzymes were not normally distributed. The median and inter-quartile range of GPx and SOD were 0.7 U/mg protein (0.5-0.9) and 0.2 U/mg protein (0.1-0.4) respectively. We observed a significant correlation between GPx and SOD activity (rho=0.3, ***p<0.001). At 1-year 34 patients experienced MACE (10 deaths, 11 MI, 6 CVA, 5 stent thrombosis and 13 new HF). There was no significant correlation between either GPx activity and MACE (p=0.12) or SOD activity and MACE (p=0.36).

CONCLUSION: In ACS patients we observed a large variance in both GPx and SOD activity. However, while some patients had low levels of antioxidant activity during the ACS presentation this was not associated with an increase in MACE at 1-year follow-up. A number of smaller studies report mixed results regarding the prognostic significance of these enzymes for cardiovascular events. To the best of our knowledge this is the largest study conducted in an acute population, and we did not identify a significant relationship between GPx or SOD activity and MACE. The cause and significance of low activity levels of these enzymes remain to be determined and is the focus of ongoing studies.