γ-glutamyltransferase and pathogenesis of cardiovascular diseases

Cardiovascular epidemiology has recently highlighted a clear link between serum γ-glutamyltransferase (GGT) and risk for stroke, infarction and cardiovascular death, associated with the evolution of atherosclerosis-related conditions, such as coronary artery and cerebrovascular disease. Thus, serum GGT is now recognized as a cardiovascular prognostic marker. However, the reasons for the association between serum GGT elevations and unfavorable prognosis remain to be defined. Histochemistry and biochemistry have provided intriguing clues, focusing new research approaches on the complex issue of monitoring and treatment of chronic cardiovascular conditions. A major challenge in cardiovascular medicine is the identification of patients prone to acute, life-threatening events. Much attention has been given to factors participating in the atheroscle-rotic degeneration of the vessel wall, particularly to those responsible for 'instability' of athero-sclerotic lesions, facilitating rupture and thrombosis. Over the last few decades, epidemiological studies have identified a large number of parameters that have the potential to become cardiovascular prognostic markers. Further work by clinical pathologists is required to determine their mechanism of action and elucidate their biological potential as new markers, thus enabling the development of preventative and/or therapeutic strategies. γ-glutamyltransferase (GGT), whose activity level in serum has recently become a novel cardiovascular prognostic marker, is an example of this. Serum γ-glutamyltransferase: epidemiological evidence of an independent relationship with cardiovascular diseases Serum GGT has long been interpreted as an index of hepato–biliary dysfunction and alcohol abuse [1], and its association with morbidity has been reported [2]. Subsequent studies suggested that GGT can have a predictive value irrespective of hepatic disease or alcohol consumption [3,4]. With regards to cardiovascular diseases, it was observed that serum GGT levels correlated with an increased risk of myocardial infarction [5,6] and of stroke [7,8]. These associations were partially explained by the known correlations of GGT with recognized factors in cardiovascular pathogenesis, such as changes in blood lipids, body mass index, hypertension, glucose intolerance, insulin resistance and Type 2 diabetes [9]. GGT levels also correlated positively with novel risk factors such as C-reac-tive protein, fibrinogen and F2-isoprostanes [10]. It was suggested that a genetic predisposition may exist to abdominal obesity, insulin resistance and other signs of the so-called metabolic syndrome, and that it may also include elevation of GGT and other liver enzymes [11]. Such an association has been unambiguously documented [12]. However, the Framingham Heart Study has recently established that an increase in serum GGT per se predicts onset of the metabolic …