Androgen deprivation therapy (ADT) is a standard treatment for patients with aggressive prostate cancer. Although ADT improves survival, it increases the risk of diabetes. Emerging evidence suggests that ADT increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that ADT may impair endothelium-dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population.
We prospectively evaluated conduit artery endothelium-dependent and -independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66 ± 7 years; 25% with diabetes) with prostate cancer before and after 3 months of ADT. High-resolution B-mode ultrasound was used to assess flow-mediated (endothelium-dependent) and nitroglycerine-mediated (endothelium-independent) brachial artery vasodilation. ADT significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium-dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively; P=0.046, allometric P=0.037). Nitroglycerine-mediated vasodilation did not change from baseline (P>0.2). The subset of participants on ADT for 6 months returned for reevaluation at 1 year. In this group, endothelium-dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively; P=0.05).
In contrast to our expectation, ADT improved endothelium-dependent vasodilation and its cessation returned endothelium-dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation.
Journal of the American Heart Association. 2015 Apr 20*** epublish ***
Paul L Nguyen, Petr Jarolim, Shehzad Basaria, Jonah P Zuflacht, Jessica Milian, Samoneh Kadivar, Powell L Graham, Andrew Hyatt, Philip W Kantoff, Joshua A Beckman
Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA (P.L.N., P.L.G., A.H.)., Department of Pathology, Brigham and Women's Hospital, Boston, MA (P.J.)., Endocrinology, Brigham and Women's Hospital, Boston, MA (S.B.)., Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (J.P.Z., J.M., S.K., J.A.B.)., Medical Oncology, Dana-Farber Cancer Institute, Boston, MA (P.W.K.).