Impact of traditional cardiovascular disease risk factors on long-term cardiovascular outcome in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study

Reporter: Gita Suneja, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 5, 2011

Presenter: Gregory Armstrong, MD
Presenter's Affiliation: St. Judes Children's Research Hospital


  • As progress in the treatment of childhood cancers has improved survival, late effects of therapy have become more pronounced and widely recognized.
  • The Childhood Cancer Survivor Study (CCSS) was established to monitor these late effects. The study has followed a cohort of patients, treated from 1970–1986, that survived at least 5 years beyond the time of study enrollment.
  • In prior analysis of the CCSS data, the cohort of survivors was found to have increased relative risk of chronic health conditions, including cardiovascular issues, as compared to their siblings.
  • In a subanalysis examining cardiovascular disease, adult survivors had 5.9 times the risk of developing congestive heart failure (CHF), 5 times higher risk of myocardial infarction (MI), and 6.3 times higher risk of developing valvular disease as compared to their siblings.
  • The risk of a cardiac event was significantly associated with anthracycline exposure > 250 mg/m2 and 15 Gy of thoracic radiation therapy.
  • Unfortunately, the risk of cardiac morbidity does not appear to plateau, but rather continues to increase even up to 30 years after diagnosis.
  • The role of traditional cardiovascular disease risk factors (CVRFs) in patients with prior exposure to cardiotoxic therapy has not been studied previously.
  • The objective of this study was to identify how traditional CVRFs modify the established increase in risk after anthracycline based therapy and thoracic radiation therapy.


  • The retrospective CCSS cohort was used for this study.
  • 14,358 patients under 21 years of age treated between 1970 and 1986 who had survived 5 year after treatment were identified at 26 pediatric cancer centers.
  • A sibling cohort was established as a control group.
  • Of the total number of cases, 13,268 were evaluable
  • Baseline information collected and followed with questionnaires includes:
    • Rates of obesity (BMI³30),
    • CVRFs requiring medical treatment (diabetes, hypertension, dyslipidemia)
    • Cardiac outcomes (coronary artery disease, congestive heart failure, valvular abnormality, stroke and arrhythmia)
  • Associations between CVRFs and cardiac outcomes were assessed using cumulative incidence of outcomes, Poisson regression, mortality cumulative incidence, and risk factor assessment.


  • Median patient age was 32 years
  • 46% of the cohort was female
  • Treated patients had a higher prevalence of hypertension (39% vs 28%), dyslipidemia (29% vs 18%), and diabetes mellitus (8% vs 5%) as compared to their siblings
  • Interestingly, siblinsg tended to be more obese than survivors (22% vs 36%)
  • By 45 years of age, the cumulative risks of cardiac disease development were increased as below:


Survivor Incidence

Sibling Incidence

Coronary artery disease (CAD)



Congestive heart failure (CHF)



Valve abnormality



  • Patients who received chest radiation therapy and had three or more CVRFs had an OR 28.2 for development of CAD, 16.2 for CHF, 55.7 for valvular abnormality, and 15.8 for arrhythmia.
  • Of the total cohort, 190 cardiac deaths occurred. The cumulative incidence of heart disease was 1% at 30 years.
  • Of all risk factors, diabetes mellitus and hypertension were considered the most dangerous. The presence of hypertension was predictive of future cardiac events.

Authors' Conclusions

  • Adult survivors of childhood cancer are at higher risk for poor cardiovascular outcomes, particularly if they were exposed to cardiotoxic therapy. The presence of traditional cardiovascular disease risk factors further increases the risk for adverse cardiovascular outcomes in this population.


  • The study highlights an important area of follow-up care for survivors of pediatric cancer, particularly those treated with radiation or anthracycline-based therapy. Understanding of increased risk associated with prior treatment and CVRF may assist healthcare teams in providing comprehensive survivorship care and surveillance.
  • Given the retrospective nature of data collection and the self-reported outcomes, the results are hypothesis-generating and causality cannot be established.
  • Furthermore, the authors attempt to isolate the effect of CVRF by analyzing the patients who had radiation alone, CVRF alone, and patients with radiation + CVRF. The latter group has astonishingly high odds of poor cardiovascular outcomes. It is unclear if radiation and CVRF are truly independent factors that can be added as the authors have done. Undoubtedly, some of the CVRF are caused by radiation or accelerated by radiation. Additionally the use of anthracyclines was not controlled for in this analysis of radiation therapy, which could lead to confounding in the results.
  • While the follow-up period is sufficiently long, patients followed on this study were treated in the early 1970s to mid 1980s, using outdated radiation techniques no longer in use. Data regarding cardiovascular outcomes for patients treated in the modern era will be of great interest when available.
  • Further investigation into CVRFs is needed to help guide follow-up and life-long surveillance of survivors of pediatric cancers, particularly those treated with cardiotoxic therapies.