Accumulating evidence suggests that androgen deprivation therapy (ADT) for prostate cancer (PCa) increases the risk of cardiovascular (CV) morbidity and mortality, though not all studies demonstrate an association. ADT may increase the risk of CV disease by causing detrimental changes in body composition, lipid profile, and insulin sensitivity. Specific populations of patients with PCa, including the elderly and patients with preexisting cardiac risk factors, appear to be the most vulnerable to CV risk secondary to ADT. Recent guidelines from the American College of Cardiology (ACC) and the American Heart Association (AHA) provide recommendations for CV risk assessment and management. In a shift from previous guidelines, the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults makes recommendations for statin therapy based on a 10-year calculated risk score, the Pooled Cohort Equation, that takes into account age, sex, race, systolic blood pressure, treatment for hypertension, history of diabetes mellitus, smoking status, and total cholesterol and high-density lipoprotein cholesterol levels rather than target lipid levels alone. The 2013 ACA/ AHA Guideline on Lifestyle Management offers specific recommendations to reduce CV risk, including avoidance of tobacco products, regular exercise, a heart-healthy diet, and maintenance of a healthy weight. While these guidelines are not specific to CV risk secondary to ADT, physicians who treat patients with PCa should be familiar with both the potential CV risks associated with ADT as well as the recommended approach to CV risk stratification, management, and prevention.
Chunkit Fung, MD, MS
Elizabeth A. Guancial, MD
Complications from ischemic cardiovascular disease (CVD) are the leading cause of morbidity and mortality worldwide.1
Due to significant advances in the understanding and treatment of advanced prostate cancer (PCa), patients are living longer with this disease. However, androgen deprivation therapy (ADT) carries with it an increased risk for metabolic changes that, while still regarded as controversial, may predispose to CVD and could compete with PCa to limit overall survival (OS). Therefore, screening for CVD and traditional risk factors that predispose to it, together with interventions to prevent and treat these conditions, are essential to ensuring that life expectancy is maximized for patients with PCa.
Does cardiovascular (CV) risk management require a unique approach when pharmacologic therapy predisposes to this complication? Importantly, it remains to be determined if screening and interventions for CVD and metabolic complications in patients with PCa treated with ADT should differ from the general population. Until data exist to support tailored therapy for patients with PCa and CVD, medical oncologists, radiation oncologists, and urologists who treat PCa with ADT should be cognizant of guidelines for CV risk assessment and treatment and address modifiable risk factors in a multidisciplinary approach together with primary care physicians, endocrinologists, and cardiologists.
Effects of ADT on CV Risk Factors
Prospective clinical trials have shown that ADT may increase the risks of cardiovascular disease by causing detrimental changes in body composition,2-6
and insulin sensitivity.3,8,9
Recent retrospective studies demonstrate an additional association of ADT with acute kidney injury.10,11
Rates of ADT-induced complications may be related to the mechanism by which androgen deprivation is achieved. Studies have demonstrated a lower risk of CV complications with orchiectomy versus endocrine therapy12
and with luteinizing hormonereleasing hormone antagonists compared with agonists.13,14
T cells express gonadotropin releasing hormone (GnRH) receptors and are present in atherosclerotic plaques. It is postulated that GnRH receptor activation by GnRH agonists could promote plaque destabilization and may contribute to the increased incidence of CV complications with this class of agents.13