Serum concentrations of vascular endothelial growth factor in advanced non-small cell lung cancer.

To the Editor: Krijgsman, Hamilton, and Mikhailidis make several points about possible mediators of the connection between serum -glutamyltransferase (GGT) activity and risk of cardiovascular disease. The authors first suggest that serum GGT may in part come from platelets and that because platelet breakdown may be increased at the sites of atheromatous plaques, people with substantial atherosclerosis would have increased serum GGT of platelet origin. Such a mechanism is possible, but it seems to require a very substantial increase in platelet turnover at plaque sites to produce a detectable increase in GGT in the plasma. Furthermore, this would not explain the associations between GGT and obesity or the metabolic syndrome, or between GGT and the prospective risk of developing type 2 diabetes. The authors also suggest a relationship between antioxidants in serum, including bilirubin and albumin, and GGT. Presumably this would be an inverse relationship, as “. . . consumption [of antioxidants] is increased in smokers and patients with vascular disease”. We cannot currently provide information on bilirubin or albumin in our study population, but it is clear that the concentration of urate (the major antioxidant in plasma) is positively correlated with the GGT activity. Finally, they cite evidence that serum GGT decreased in hypertriglyceridemic patients treated with fibrates. This would be consistent with a role for fatty liver in producing increased serum GGT and being associated with an increase in cardiovascular risk, and it offers a possible means of risk reduction. However, the mean decrease in GGT was small, alanine aminotransferase was unchanged, and aspartate aminotransferase actually increased. A shortterm trial of fibrate treatment in patients with alcoholic fatty liver (1 ) failed to lower serum GGT (or aspartate aminotransferase or alanine aminotransferase) significantly, although serum triglycerides fell substantially. We do not know, at this stage, whether GGT would remain a significant cardiovascular risk factor if triglycerides and VLDL were lowered by treatment, but the published epidemiologic studies suggest that it would.