Paclitaxel chemotherapy and vascular toxicity as assessed by flow-mediated and nitrate-mediated vasodilatation.

BACKGROUND: Antitumor activity of paclitaxel is based on promotion of abnormal microtubule (MT) assembly but it is also considered to have significant pro-inflammatory and anti-angiogenic effects in vivo and thus may cause vascular dysfunction. METHODS: We studied 27 women treated with paclitaxel-containing combinations for breast or ovarian cancer. The control group was represented by 10 women with carcinoma of the uterine cervix who received low doses of weekly cisplatin as radiation sensitizer. We measured endothelial-dependent flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD) of the right brachial artery by ultrasonography, as well as levels of the inflammatory cytokines TNF-alpha and IL-6 before and after chemotherapy. RESULTS: Patients who received paclitaxel and an anthracycline had the most marked reduction in both FMD (p=0.005) and NMD (p=0.027). A significant reduction in FMD was also observed in patients treated with weekly paclitaxel (p=0.045), whereas NMD was not affected (p=0.421). Although TNF-alpha and IL-6 levels were different among chemotherapy groups after treatment, no significant differences were observed between levels of both markers before and after chemotherapy. CONCLUSION: Treatment with paclitaxel-containing combinations impairs endothelial function in vivo but endothelial function deterioration is not related to the serum levels of inflammation markers.

Precursors of atherosclerosis in a random sample from a Hellenic population: the Athens Study.

BACKGROUND: Atheromatosis, the principal lesion in atherosclerotic cardiovascular disease, is associated with increased levels of blood pressure, serum cholesterol, cigarette smoking and other variables. As these lesions are thought to appear first in childhood, this study was designed to assess the levels of these atherosclerotic precursors in children living in Athens, Greece. METHODS: The following parameters were measured in a random sample of 4117 school children aged 6-18 years, living in the centre of Athens: body mass index, blood pressure, serum lipids, glucose, uric acid, calcium, phosphorus, creatinine, and haematocrit. RESULTS: Mean levels of blood pressure, total cholesterol, cigarette smoking and body mass index increased with age in both sexes, levels being similar to those of children in developed countries. Smoking started at elementary school, and by puberty had reached adult levels. High levels of systolic blood pressure ( > or = 130 mmHg) and total cholesterol ( > or = 5.68 mmol/l) were seen in 22% and 13% of children respectively. Triglyceride and glucose levels did not increase with age; high-density lipoprotein cholesterol decreased and uric acid increased from 14 to 18 years, but only in boys. Levels of body mass index, total cholesterol, triglycerides, high-density lipoprotein and uric acid above the mean population values were found in 25% of children, and glucose levels above the mean in 50%. Multiple linear regression analysis showed a positive correlation between systolic blood pressure and age, body mass index, uric acid, sex, glucose, triglycerides and high-density lipoprotein cholesterol (in that order), and between diastolic blood pressure and age, body mass index and triglycerides. CONCLUSIONS: These findings indicate that the levels and prevalence of precursors of atherosclerosis are higher than expected in a southern European population, and are similar to those found in developed countries. This would indicate a need for greater awareness among the Greek population of preventive measures against developing cardiovascular disease.