Markers for Acute Chemotherapy induced Cardiovascular changes.

Long-term survivors of testicular cancer cured with cisplatin based chemotherapy are at increased risk of developing cardiovascular disease. One of the potential mechanisms behind the development of cardiovascular disease is endothelial damage. We hypothesise that a chemotherapy induced reduction in circulating endothelial (progenitor) cells and accumulation of advanced glycation end products (AGEs) due to chemotherapy induced oxidative stress, might contribute to cardiovascular damage. In this prospective non-randomised cohort study in 50 patients with disseminated testicular cancer, circulating endothelial cells and accumulation of AGEs (reflected by skin autofluorescence) will be measured before, during and after (up to 1 year) cisplatin based chemotherapy and related to cardiovascular changes, as assessed by cardiovascular funcyion tests. With this study we hope to get insight into the underlying mechanisms of chemotherapy induced cardiovascular damage and to find feasible surrogate markers for this damage, which may contribute to the early detection of cardiovascular toxicity and to the design of intervention strategies.

1. The number of circulating endothelial (progenitor) cells may be reduced during chemotherapy and correlate to the development of cardiovascular disease;
2. Oxidative stress due to chemotherapy may lead to an increased accumulation of Advanced Glycation End products (AGEs) in blood vessels, contributing to endothelial damage.

The number of circulating endothelial cells, endothelial marker proteins and accumulation of AGEs (estimated by measuring skin autofluorescence with an AGE-reader) will be determined before, during and after chemotherapy. Cardiovascular status (intima-media thickness of the carotid artery, baroreflex sensitivity and 24-hour ambulatory blood pressure measurement) will be evaluated before start of chemotherapy, within 4 weeks after completion of chemotherapy and 1 year after start of chemotherapy.