Abstract

Background: Serum gamma-glutamyltransferase (γ-GT) is recognized as a risk factor for cardiovascular diseases (CV). Traditional cardiovascular risk factors mediate endothelial dysfunction. Aim: to evaluate a possible correlation between serum γ-GT and endothelium-dependent vasodilation in naïve hypertensives. Methods: We enrolled 500 hypertensives. Endothelial function was studied by strain-gauge plethysmography. Receiver operating characteristic (ROC) analysis was used to assess the predictive value of γ-GT and to identify the optimal cut-off value of the same variable for endothelial dysfunction. Results: At univariate linear analysis peak percent increase in acetylcholine (ACh)-stimulated vasodilation was inversely related to γ-GT (r = −0.587), alanine aminotransferase (ALT) (r = −0.559), aspartate aminotransferase (AST) (r = −0.464), age (r = −0.171), body mass index (BMI) (r = −0.152), and fasting glucose (r = −101). In the stepwise multivariate regression model, endothelium-dependent vasodilation was significantly related to γ-GT (β = −0.362), ALT (β = −0.297), AST (β = −0.217), estimated glomerular filtration rate (e-GFR) (β = 0.199), gender (β = 0.166), and smoking (β = −0.061). The ROC analysis demonstrated that the accuracy of γ-GT for identifying patients with endothelial dysfunction was 82.1%; the optimal γ-GT cut-off value for discriminating patients with this alteration was 27 UI/L. Conclusions: Serum γ-GT values, within the normal range, are significantly associated with endothelial dysfunction in hypertensives, and may be considered a biomarker of early vascular damage.

Highlights

  • Gamma-glutamyltransferase (γ-GT) is a glycoprotein located on the plasma membranes of most cells and organ tissues, especially of hepatocytes

  • Thisanalysis additional analysis dividing the whole study population into two sized subgroups. This additional analysis showed that the strength of the relationships between the key risk factors

  • Findings obtained in this study demonstrate, for the first time, the association between serum γ-GT within the normal range and endothelial dysfunction, evaluated by strain-gauge plethysmography, in a very large and well-characterized population of never-treated hypertensive patients

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Summary

Introduction

Gamma-glutamyltransferase (γ-GT) is a glycoprotein located on the plasma membranes of most cells and organ tissues, especially of hepatocytes. Serum γ-GT levels are routinely measured when hepatic/biliary disease and/or alcohol abuse are suspected [1], and it has recently been recognized as a risk factor for metabolic alterations [2], and chronic renal [3] and cardiovascular diseases (CV) [4,5,6,7]. These effects seem to be mediated by the capacity of γ-GT to increase the production of reactive oxygen species (ROS) in the presence of some transition metal such as iron [4,8].

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