Reduced glutathione peroxidase activity predicts increased cardiovascular risk following an acute coronary syndrome.

Abstract

Background: Glutathione peroxidase (GPx) is an antioxidant enzyme that comprises a primary defence against oxidative stress.  Deficiencies in GPx have been associated with progression of atherosclerosis and arterial thrombosis.  However, the relationship between GPx activity and clinical outcomes in acute coronary syndromes (ACS) remains controversial.  This study examined the relationship between plasma GPx activity and subsequent major adverse cardiovascular events (MACE) in ACS patients. Method: In this prospective cohort study, 262 ACS patients had their plasma GPx activity measured using a colourimetric enzyme assay.  Patient demographics, clinical variables and MACE, a composite of death, non-fatal myocardial infarction, ischaemic stroke and acute heart failure, were collected. Results: At 1 year follow-up, 34 (13%) patients experienced MACE.  When the MACE rate was examined by quartiles of GPx activity, a significant decrease in MACE was demonstrated with increasing quartiles of GPx activity ( P = 0.04).  The event rate for patients in the lowest quartile of GPx activity was 19.6% compared to 7.9% for the upper quartile.  Levels of GPx activity were significantly lower in diabetic patients compared to non-diabetic patients ( P = 0.02), and lower in males compared to females ( P = 0.03).  GPx activity was a moderate predictor of MACE by receiver operator characteristic analysis with an area under the curve of 0.62 ( P = 0.02). Conclusion: We have demonstrated that lower levels of GPx activity are associated with an increased risk of MACE at 1 year following an ACS.  Low levels of GPx activity may represent a decreased defence against oxidant-mediated cardiovascular damage.