Study Shows Childhood Cancer Survivors Face Higher Risk of Cardiovascular Disease

All survivors of childhood cancer face a higher long-term risk of cardiovascular diseases and should be screened for a wide range of potential heart conditions, according to a new study led by Steven E. Lipshultz, M.D., professor and chair of pediatrics and executive associate dean for child health at the Miller School.

The groundbreaking study, published online March 5 ahead of appearing in a print issue of the Journal of Clinical Oncology, points to the importance of increased cardiovascular screening for cancer survivors regardless of the form of treatment they received as a child. “Increased screenings will allow physicians to identify the highest-risk patients and target preventive strategies before the onset of cardiac symptoms or serious cardiovascular disease,” Lipshultz said.

Prior studies have shown that survivors of childhood cancer who were treated with anthracycline chemotherapy or cardiac irradiation are at increased risk for cardiovascular disease. However, the new Miller School study found that even cancer survivors who had not been exposed to cardiotoxic treatments or radiation of the cardiac tissues still have an extremely high risk of cardiomyopathy, systemic cardiac inflammation and other cardiovascular problems. Survivors are also more likely to have traditional risk factors for atherosclerotic disease, including elevated cholesterol, obesity and insulin resistance.

“This is the first report to examine simultaneously the risk of cardiomyopathy and the risk of atherosclerotic cardiovascular disease in all childhood cancer survivors,” Lipshultz said. “This is critical information for developing strategies to improve cardiovascular outcomes in this population. Hopefully, the findings will change the standard of care for how pediatric cancer survivors are followed and managed as they grow into adulthood.”

Cardiovascular-related complications are of particular concern for the more than 325,000 childhood cancer survivors in the U.S. For the 30 years after cancer treatment, survivors are eight times more likely to die from cardiac causes and 15 times more likely to experience congestive heart failure than the general population.

The study, “Cardiovascular Status of Childhood Cancer Survivors Exposed and Unexposed to Cardiotoxic Therapy,” was funded by the National Cancer Institute’s Office of Cancer Survivorship. Lipshultz and the study’s co-authors – including David C. Landy M.P.H., a student in the University of Miami’s M.D./Ph.D. program, Gabriela Lopez-Mitnik, M.S., M.Phil., senior research associate in pediatrics, and Tracie L. Miller, M.D., professor of pediatrics and director of pediatric clinical research – evaluated a large cohort of representative childhood cancer survivors in Western New York.

The Miller School-led research team assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer – including those who had undergone cardiotoxic treatments and those who had not– and compared the findings with those in sibling controls. The assessments were conducted at a median interval of 11 years after the cancer diagnosis.

The study found that the 156 cancer survivors who had undergone cardiotoxic treatments had below normal mass and wall thickness in the left ventricle, as well as other cardiac problems. However, the 45 survivors who did not receive cardiotoxic treatments also had below normal left ventricle mass, and females in this same group had below-normal wall thickness, and elevated NT-proBNP, an important marker of increased cardiac stress.

“The current standard of care calls for cardiac screenings only for childhood cancer survivors who have been exposed to chemotherapy previously known to be cardiotoxic to survivors,” said Lipshultz, who is also chief of staff at Holtz Children’s Hospital. “This study supports an expansion of that standard to encompass pediatric cancer survivors who received radiation treatments, even for malignancies outside the chest area, and in fact targeted screening for cardiovascular risk factors in all survivors of childhood cancer.”

While more research is needed to determine the medical processes and pathways that lead to increased cardiac risk among cancer survivors, Lipshultz said radiation treatments may affect a child’s hypothalamus and pituitary glands, reducing the output of human growth hormones necessary to grow normal heart muscle.

In the meantime, recognized cardiac biomarkers, such as serum cholesterol, NT-proBNP, and hs-CRP, may help physicians identify patients in greatest need of more detailed cardiovascular assessment, Lipshultz said.

Other study co-authors included researchers from Brigham and Women’s Hospital in Boston and the University of Rochester School of Medicine and Dentistry in Rochester, New York.

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