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
Summary
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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