Effect of age and gender on the relationship between alcohol consumption and serum GGT: time to recalibrate goals for normal ranges.

AIMS: While serum gamma-glutamyltransferase (GGT) enzyme activity is a well established biomarker of excessive alcohol consumption and liver dysfunction, recent studies have also implicated it as a predictor of morbidity due to extrahepatic causes. Therefore, further information on the associations between ethanol intake and GGT activities in apparently healthy individuals appears warranted. METHODS: Data on alcohol consumption and serum GGT activities were collected from 18,899 individuals (8807 men, 10,092 women), mean age 48 years and range 25-74 years, who participated in a national cross-sectional health survey. Alcohol use was assessed by detailed questionnaires and the study population was subsequently divided into subgroups according to age and gender. Body mass index and smoking were used as covariates in all analyses. RESULTS: In men over 40 years, a reported regular consumption of 8 standard ethanol doses ('dose' = 12 g ethanol) or more per week was found to lead to a significant elevation in serum GGT activities, whereas those below 40 showed first significant changes not until the reported ethanol intake exceeded 14 doses per week. For women, the corresponding threshold levels were four and seven standard ethanol doses, respectively. CONCLUSION: The data pertaining to the present population sample indicate that rather low levels of reported regular ethanol consumption lead to elevated levels of GGT and that age over 40 markedly enhances the impact of alcohol consumption on GGT activity. The present findings should form the basis for defining safe levels of ethanol consumption and in recalibrating goals for normal limits in the clinical use of GGT measurements.

Studies on the effects of heparin products on pregnancy-associated plasma protein A.

BACKGROUND: Intravenous low molecular weight (LMWH) and unfractionated heparin (UFH) increase the circulating concentrations of pregnancy-associated plasma protein A (PAPP-A), a novel cardiac risk marker, in haemodialysis and coronary angiography patients. METHODS: To further investigate the mechanisms of heparin effects, free PAPP-A was analysed in serial serum samples collected during haemodialysis (intravenous LMWH), carotid endarterectomy or abdominal aortic aneurysm surgery (intravenous UFH), treatment at intensive care unit (subcutaneous LMWH), and coronary angiography (intravenous bivalirudin). PAPP-A was extracted from plaque tissue samples of endarterectomy and aneurysm patients. The interaction between heparin products and free PAPP-A was studied with gel filtration. RESULTS: After intravenous UFH and LMWH free PAPP-A increased significantly but bivalirudin had no effect. After LMWH bolus in haemodialysis patients 85% of free PAPP-A was cleared with a half-life of 13.1 min and the rest with a half-life of 96.6 min. Subcutaneous LMWH led to lower and slower free PAPP-A elevation. PAPP-A extracted from plaque tissues was in free form and extraction was strongly enhanced by LMWH. Heparin products increased the molecular size of free PAPP-A. CONCLUSIONS: The heparin-induced PAPP-A elevation is seen in various patients and should be taken into account when PAPP-A is studied as a biomarker.