Glutathione peroxidase-1 activity, atherosclerotic burden, and cardiovascular prognosis

Recent findings suggest that erythrocyte intracellular glutathione peroxidase-1 (GPX-1) activity is related inversely to future cardiovascular events. The aim of this study is to evaluate the association of GPX-1 activity to extent of atherosclerosis, as well as its long-term prognosis in context with atherosclerotic burden. In a prospective study, we included 508 patients before coronary angiography. Atherosclerosis of carotid and leg arteries was documented using sonographic methods. Blood samples,were drawn after an overnight. fasting period, and GPX-1 activity was determined in washed erythrocytes. GPX-1 activity tended to decrease with increasing numbers of atherosclerotic vascular beds, so that patients without clinically relevant atherosclerosis had GPX-1 activity of 49.3 U/g heinoglobin compared with 46.0 U/g hemoglobin in patients with prevalent atherosclerosis in all 3 vascular beds (p = NS). Follow-up data (median 6.5 years) were available for 504 patients (99.2% and 96 patients (19.0%) experienced cardiovascular events (cardiovascular death, infarction, and stroke). The event rate was inversely associated with level of GPX-1 activity divided into tertiles (hazard ratio 2.3, 95% confidence interval 1.4 to 4.0 for lowest vs highest tertile of GPX-1 activity, p=0.002, adjusted). The highest event rate was found in persons with low GPX-1 activity and multivascular atherosclerosis (event rate 36.9%, p < 0.0001). In conclusion, decreased red blood cell GPX-1 activity is associated with increased cardiovascular risk according to the extent of atherosclerosis. (c) 2007 Elsevier Inc. All rights reserved.