Glutathione Peroxidase-1 and Homocysteine for Cardiovascular Risk Prediction

OBJECTIVES: This prospective study was designed to evaluate the effect of joint determination of two important contrary biomarkers--homocysteine and glutathione peroxidase (GPx)-1--on cardiovascular risk stratification. BACKGROUND: Homocysteine plasma levels have been associated with cardiovascular risk. Experimental data suggest that antioxidative GPx-1 activity modulates cardiovascular risk associated with homocysteine. METHODS: In 643 patients with coronary artery disease, we performed a prospective study to assess the risk of homocysteine plasma levels and GPx-1 activity on long-term cardiovascular risk with a median follow-up of 7.1 years. RESULTS: Both homocysteine and GPx-1 were among the strongest univariate predictors of future cardiovascular risk, even after adjustment for cardiovascular confounders. Homocysteine levels were significantly elevated in individuals with future cardiovascular events (15.4 vs. 13.4 micromol/l; p < 0.0001); GPx-1 activity was lower (45.3 +/- 13.1 vs. 50.2 +/- 11.0 U/g hemoglobin; p < 0.0001). In patients with GPx-1 activity below the median value, homocysteine plasma levels above the median were associated with a 3.2-fold (95% confidence interval 1.8 to 5.6; p < 0.0001) increase in cardiovascular risk, whereas it lost its independent risk prediction in individuals with increased antioxidative capacity, as reflected by high GPx-1 activity. In contrast to single determination, combined assessment revealed a significant increase in the area under the curve of cardiovascular risk predictive models from 0.72, including traditional risk factors to 0.75 and also including homocysteine levels and GPx-1 activity. CONCLUSIONS: Plasma homocysteine levels and GPx-1 activity are complementary in identifying individuals at high cardiovascular risk. Joint determination of both biomarkers provides substantial information on top of classic risk factors in cardiovascular risk assessment.