Fitness, Cardiovascular Disease and Mortality in Childhood Cancer Survivors: A St. Jude Lifetime Cohort

Childhood cancer survivors are at increased risk of premature cardiovascular morbidity and all-cause mortality compared to peers. Data suggest that higher levels of physical activity reduce risk of cardiovascular morbidity/mortality within the general population. However, associations between specific measures fitness and new onset cardiovascular morbidity /mortality are not described. PURPOSE: To assess the associations between fitness and incident moderate, serious, disabling/life-threatening cardiovascular disease (Common Terminology and Criteria for Adverse Events grades 2-5) as well as the associations between fitness and all-cause mortality in adult survivors of childhood cancer. METHODS: Participants (n = 1,675, mean ± SD age: 35.2 ± 8.4 years, 49.0% male) completed a baseline, self-limited graded exercise test (using the Bruce protocol) to assess peak maximal oxygen consumption (VO2peak), and the FRIEND equation was used in the denominator to calculate percent of predicted VO2peak. Those in the lowest quartile were categorized as having impaired fitness (<58% of their predicted VO2peak). Associations between impaired fitness and incident cardiovascular disease (median follow-up 3.4 years, 1.1-5.4) and all-cause mortality (median follow-up 3.9 years, 1.1-5.4) were evaluated with multivariable Cox-proportional hazard regression, adjusted treatment, lifestyle factors, baseline cardiovascular disease, and risk factors for cardiovascular disease. RESULTS: Survivors who had impaired fitness had no increased risk for incident cardiovascular disease compared to survivors without impaired fitness (Hazard ratio: 1.28; 95% confidence interval: 0.77-2.10). However, survivors with impaired fitness had increased risk for all-cause mortality (Hazard ratio: 2.60; 95% confidence interval: 1.58, 6.34) compared to survivors without impaired fitness. Importantly, all-cause mortality decreased by 3.0% for one unit increase in their percent of predicted VO2peak. CONCLUSIONS: Low fitness is not associated with new onset of cardiovascular morbidity but is independently associated with all-cause mortality. Longer follow-up is necessary to determine the contribution of fitness to long-term develop of cardiovascular morbidity.