Associations between Cardiopulmonary Fitness and Cardiovascular Events in Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort

PURPOSE: Childhood cancer survivors are at increased risk of premature cardiovascular events compared with peers. Increased cardiopulmonary fitness reduces the risk of cardiovascular morbidity/mortality within the general population but is poorly described in cancer survivors. We examined the associations between fitness and cardiovascular events in childhood cancer survivors. METHODS: Participants ( n = 2433) completed a baseline, cardiopulmonary exercise test (CPET) to assess peak maximal oxygen consumption (V̇O 2peak ). Metabolic equivalents (METs) were calculated by dividing V̇O 2peak by 3.5 mL·kg 1 ·min, and peak METs achieved on CPET were used to document cardiopulmonary fitness. In addition, we categorized participants (based on age- and sex-matched controls) as low (<50th percentile of achieved METs) and normal (≥50th percentile). Subsequent cardiovascular disease was graded with the Common Terminology Criteria for Adverse Events v. 4.03. Associations between peak METs and subsequent cardiovascular disease in survivors were evaluated with multivariable Cox proportional hazard regression, adjusted for cancer treatment, lifestyle, baseline cardiovascular disease, and cardiovascular risk factors. In addition, a univariate analysis was conducted to examine the peak METs achieved on the CPET in survivors who died from a cardiovascular event and those who did not. RESULTS: Each 1-MET increase on the survivor's CPET performance decreased the risk of incident cardiovascular disease (hazard ratio, 0.80; 95% confidence interval, 0.72-0.90). Among survivors with low baseline cardiopulmonary fitness, those who achieved 1 MET higher value on their CPET had a lower risk of incident cardiovascular disease (hazard ratio, 0.78; 95% confidence interval, 0.65-0.96). The average peak METs achieved ere lower (5.9 ± 2.17) among survivors who died from cardiovascular disease compared with those who did not (7.6 ± 2.5). CONCLUSIONS: Higher cardiopulmonary fitness was associated with a lower risk of incident cardiovascular disease. Early identification of survivors with low cardiopulmonary fitness provides opportunities for risk mitigation through promotion of regular physical activity.