Miller School Study Offers Tools to Prevent Atherosclerosis in Survivors of Childhood Cancer
In a study that provides practical tools for identifying pediatric cancer survivors at high risk for premature death from atherosclerosis, Miller School researchers found that teenagers and young adults who survived childhood cancer have increased odds of already having blocked arteries, as well as an elevated risk of suffering a myocardial infarction, stroke, or coronary death over the next 30 years.
But the study published in the February issue of the American Heart Journal and led by Steven E. Lipshultz, M.D., professor and chair of pediatrics and associate executive dean for child health, found that the cardiometabolic health of young cancer survivors was not significantly different from a similarly aged sibling who had never battled cancer. The finding suggests that poor cardiometabolic health of childhood cancer survivors is not strongly associated with their cancer or their treatment, but with their physical inactivity, a modifiable risk that can be targeted early to prevent premature death.
“We found the type of the cancer and the type of chemotherapy didn’t necessarily play a role,’’ said Lipshultz, a pediatric cardiologist and pioneer in the field of cardio-oncology who first documented the late-effects of chemotherapy on the hearts of childhood cancer survivors. “Instead we found the suggestion that the more sedentary childhood cancer survivors had the highest risk factors. We used the siblings as a control but they turned out to be really important. Without them, we could have incorrectly attributed the increased risks to the cancer survivors’ cancer therapies.’’
Supported by the National Cancer Institute’s Office of Cancer Survivorship, researchers on the study, “Aggregating traditional cardiovascular disease risk factors to assess the cardiometabolic health of childhood cancer survivors: An analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study,’’ abstracted the medical records of dozens of childhood cancer survivors who were treated in the Finger Lakes region of New York and Pennsylvania.
Then they had the survivors and a similarly aged sibling undergo a daylong battery of tests, from which they aggregated the cardiovascular disease risk factors of both groups with one of two validated cardiovascular disease risk aggregation instruments, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY), or the Framingham Risk Calculator (FRC).
Established decades ago by previous NIH studies, PDAY and FRC both score such risk factors as age, gender, smoking status, cholesterol and blood pressure, and express the scores as ratios. The PDAY odds ratio represents the increased odds of currently having an advanced coronary artery lesion, and the FRC risk ratio represents the increased risk of having a myocardial infarction, stroke, or coronary death in the next 30 years. Ratios for both are relative to an individual of similar age and sex without cardiovascular risk factors.
For the American Heart Journal study, Lipshultz and his team found that a significant proportion of the childhood cancer survivors – 17 percent of those scored with PDAY, and 12 percent of those in the FRC group – had an odds or risk ratio greater than four, meaning they were at least four times more likely to have an advanced coronary artery lesion now, or to have a myocardial infarction, stroke, or coronary death in the next 30 years than individuals of the same gender and similar age without cardiovascular disease risk factors.
However, the researchers also found that the average scores for both survivors and their siblings were similar, 2.32 versus 2.25 for the PDAY group, and 1.70 versus 1.63 for the FRC group, suggesting that their risk factors were attributable more to their sedentary lifestyle than cancer or cancer therapies.
Lipshultz and his co-authors concluded their study by proposing that clinicians who care for childhood cancer survivors employ PDAY or FRC — both easily accessible and inexpensive — to identify cancer survivors at elevated risk for cardiovascular disease and target them with prevention and therapeutic strategies before their disease progresses.
“An important mission of pediatrics is the identification during childhood of risk factors for clinically significant disease over one’s lifespan to target those at highest risk and personalize risk-reduction strategies to prevent disease and maintain health,’’ Lipshultz said. “Here is a way to identify that 12 or 15 percent most at risk of dying 30 years down the road and preventing that from happening. You don’t need fancy equipment. You don’t need to be at a fancy academic center. The things that go into these calculator equations are really simple, and today you can download apps for them on your phone.’’
In addition to Lipshultz, other co-authors from the Miller School included lead author David C. Landy, M.P.H., a student in the Miller School’s M.D./Ph.D. program completing his Ph.D. in epidemiology; Tracie L. Miller, M.D., professor of pediatrics and director of the Division of Pediatric Clinical Research; and Gabriela Lopez-Mitnik, M.S., M.Phil., a biostatistician in the Division of Pediatric Clinical Research.