Armstrong et al evaluated the prevalence of self-reported hypertension, diabetes mellitus, dyslipidemia, and obesity and the incidence of self-reported major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmias in adult survivors of childhood cancer in the Childhood Cancer Survivor Study.1 They concluded that survivors who received chest radiation or anthracycline chemotherapy are at high risk for serious cardiac events, and when these therapeutic exposures are combined with cardiovascular risk factors, in particular hypertension, risk is significantly increased.
In individuals with hypertension and a history of chest radiation, the risk is increased above that expected in a simple additive risk model. These findings are of considerable clinical importance and are almost identical to those observed among patients treated with cardiotoxic therapy during adulthood, as described below, demonstrating that aggressive management of cardiovascular risk factors among recipients of cardiotoxic therapy could help reduce the morbidity associated with cardiac disease among cancer survivors.
Adult Study
A study in adults, led by Armenian,2 estimated the magnitude of risk of cardiovascular risk factors after autologous and allogeneic hematopoietic cell transplantation and explored the impact of the cardiovascular risk factors on the subsequent development of cardiovascular disease among hematopoietic cell transplantation survivors. The methodology differed from the Childhood Cancer Survivor Study: For example, cardiovascular risk factors and cardiovascular outcomes were clinically validated using American Heart Association criteria; the cardiovascular risk factors preceded the diagnosis of the cardiac disease; and the National Health and Nutrition Examination Survey (NHANES) was used for population-based comparison.
Median age in the transplantation cohort was 50 years at study participation, with 63% non-Hispanic whites, whereas the Childhood Cancer Survivor Study cohort had a median age of 37 years old, with 88% non-Hispanic whites. The prevalence of hypertension among older childhood cancer survivors was 40.2%, compared with 25% among age-matched siblings. In the transplantation population restricted to the 2005 to 2008 era, hypertension was diagnosed in 37% of the survivors and 35% of the general population.
Twenty-three percent of the childhood cancer survivors reported dyslipidemia, compared with 14% of the siblings. Moreover, 46% of the hematopoietic cell transplantation survivors developed dyslipidemia, compared with a prevalence of 40% in the general population. The prevalence of diabetes was 15% vs 10% in the childhood cancer study and 17.3% vs 8.5% in the transplantation survivor study.
The conclusion from these comparisons is that cardiovascular risk factors are prevalent among both childhood cancer survivors and survivors of adult-onset cancer and that the prevalence of certain cardiovascular risk factors (dyslipidemia) is higher among the transplantation survivors when compared to childhood cancer survivors at comparable ages.
Key Findings
The Childhood Cancer Survivor Study demonstrates that the risk for cardiac events increases with increasing number of cardiovascular risk factors among patients exposed to cardiotoxic therapy (chest radiation and anthracyclines).1 Among hematopoietic cell transplantation survivors, the 10-year incidence of cardiovascular disease increased by the number of cardiovascular risk factors: 4.7% with no cardiovascular risk factors, 7.0% with one cardiovascular risk factor, and 11.2% with at least two cardiovascular risk factors (P < .01); the risk was especially high (15.0%) in patients with multiple cardiovascular risk factors and pre–hematopoietic cell transplantation exposure to anthracyclines or chest radiation.2
Finally, the Childhood Cancer Survivor Study demonstrated an interaction between cardiovascular risk factors (especially hypertension) and cardiac disease. Again, these findings are similar to those observed among adult autologous hematopoietic cell transplantation recipients,3 in whom the presence of hypertension among recipients of high-dose anthracycline therapy (≥ 250 mg/m2) resulted in a 35-fold increased risk of heart failure. Furthermore, the risk was nearly 27-fold higher among high-dose anthracycline recipients with diabetes.
These findings demonstrate conclusively that hypertension, diabetes, and dyslipidemia are prevalent in cancer survivors across the entire age spectrum and are critical modifiers of anthracycline-related myocardial injury and radiation-related coronary artery disease, creating targeted populations for aggressive intervention. ■
Disclosure: Dr. Bhatia reported no potential conflicts of interest.
Dr. Bhatia is Professor and Chair, Department of Population Sciences, Ruth Ziegler Chair in Population Research, and Associate Director, Population Sciences, Program Co-Leader, Cancer Control and Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California.
References
1. Armstrong GT, Oeffinger KC, Chen Y, et al: Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. J Clin Oncol. September 3, 2013 (early release online).
2. Armenian SH, Sun CL, Vase T, et al: Cardiovascular risk factors in hematopoietic cell transplantation (HCT) survivors: Role in development of subsequent cardiovascular disease. Blood 120:4505-4512, 2012.
3. Armenian SH, Sun CL, Shannon T, et al: Incidence and predictors of congestive heart failure following autologous hematopoietic cell transplantation. Blood 118:6023-6029, 2011.
