Glutathione peroxidase-1 and homocysteine for cardiovascular risk prediction -: Results from the AtheroGene study

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 μ mol/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. © 2005 by the American College of Cardiology Foundation.