Associations Between Fitness And Cardiovascular Disease In Childhood Cancer Survivors: A St. Jude Lifetime Cohort Study

Abstract

Progress in biology and therapy for pediatric malignancies has resulted in dramatic improvement in survival in children with cancer. Unfortunately, childhood cancer survivors are at an increased risk for late mortality and morbidity. Physical fitness may mitigate the risk of chronic disease within childhood cancer survivors. PURPOSE: To evaluate the associations between baseline physical fitness and the onset of chronic cardiovascular disease in childhood cancer survivors. METHODS: Survivors of childhood cancer (n=501, mean ± SD age: 35.5 ± 8.2 years, 47.3% male) underwent a baseline, self-limited graded exercise test to assess peak maximal oxygen consumption (VO2peak). Quartiles of fitness were calculated from the percentage of age and sex predicted VO2peak. Moderate to severe chronic cardiovascular disease (grade 2-4) was assessed at baseline and during a follow-up period (3.6 ± 1.0 years) using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03. A multivariable Cox-proportional hazard regression was used to examine the risk of developing cardiovascular disease. RESULTS: Survivors within the lowest quartile of fitness (< 60% of predicted) were at a significantly increased risk of developing cardiovascular disease compared to the survivors in the three higher quartiles of fitness (Hazard Ratio: 1.54; 95% Confidence Interval: 1.01, 2.36), adjusting for age, sex, and prevalent cardiovascular disease. Interaction between prevalent disease and VO2 was not significant. CONCLUSION: Low fitness is associated with new-onset of moderate to severe cardiovascular disease regardless of previous cardiovascular disease. Importantly, survivors with the lowest fitness may benefit from increasing their cardiopulmonary fitness the most. Interventions specifically targeting cardiopulmonary fitness could help reduce future cardiovascular illness in childhood cancer survivors.