Plasma bilirubin and gamma-glutamyltransferase activity are inversely related in dyslipidemic patients with metabolic syndrome: Relevance to oxidative stress

Background: Subnormal levels of plasma bilirubin levels are associated with premature coronary artery disease and cardiovascular morbidity. Plasma gamma-glutamyltransferase (GGT) activity is linked to bilirubin level in hepatic disease and elevated GGT is equally associated with hepatic steatosis, a frequent feature of metabolic syndrome (MS). In order to assess the potential relationship between GGT activity and bilirubin levels in subjects exhibiting features of the metabolic syndrome, we determined circulating bilirubin levels and GGT activity in a cohort of dyslipidemic patients. Methods and results: This cross-sectional study involved patients (n = 1433) displaying atherogenic dyslipidemia in primary prevention referred to our Prevention Center. Among these patients, 25% presented with MS as defined by recent NCEP ATP III criteria. Circulating levels of transaminases, as well as GGT activity, were elevated in MS patients; by contrast, bilirubin concentrations were significantly lower in such patients as compared to those lacking this syndrome (p < 10-4 for all comparisons). Comparisons of patient groups on the basis of the number of MS criteria which were concomitantly present revealed a progressive decrease in mean bilirubin levels; this reduction paralleled a progressive increase in mean GGT activity as a function of the number of MS components in the overall population (p value for trend < 10-4). Conclusion: Elevation in systemic GGT activity, which is characterized by extended generation of ROS, together with potentially deficient bilirubin-mediated antioxidative capacity of plasma, may therefore constitute key components of the systemic oxidative stress typical of metabolic syndrome. (C) 2010 Elsevier Ireland Ltd. All rights reserved.