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

Wogksch MD; Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN.
Ware ME; O’Neil ST; Nolan VG;Smeltzer MP; Mzayek F; Mulrooney DA; Ehrhardt MJ; Dixon SB; Rhea IB; Srivastava DK; Armstrong GT; Hudson MM;
Ness KK;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2025 Jul 01.
Date of Electronic Publication: 2025 Jul 01.

Purpose: Childhood cancer survivors are at increased risk of premature cardiovascular events compared to peers. Increased cardiopulmonary fitness reduces the risk of cardiovascular morbidity/mortality within the general population but are poorly described in cancer survivors. We examined the associations between fitness and cardiovascular events in childhood cancer survivors.
Methods: Participants (n = 2,433) completed a baseline, cardiopulmonary exercise test (CPET) to assess peak maximal oxygen consumption (VO2peak). Metabolic equivalents (METs) were calculated by dividing VO2peak by 3.5 ml·kg1·min and peak METs achieved on CPET was used to document cardiopulmonary fitness. Additionally, we categorized participants (based on age- and sex-matched controls) as low (<50th percentile ofachieved 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. Additionally, 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 [HR] 0.80, 95% Confidence interval [CI] 0.72, 0.90). Among survivors with low baseline cardiopulmonary fitness, those who achieved 1 MET higher value on their CPET had lower risk of incident cardiovascular disease (HR:0.78, 95% CI 0.65, 0.96). The average peak METs achieved was lower (5.9 ± 2.17) among survivors who died from cardiovascular disease compared to those who did not (7.6 ± 2.5).
Conclusions: Higher cardiopulmonary fitness was associated with lower risk for incident cardiovascular disease. Early identification of survivors with low cardiopulmonary fitness provides opportunities for risk mitigation through promotion of regular physical activity.
Competing Interests: Conflict of Interest and Funding Source: Support to St. Jude Children’s Research Hospital provided by the National Cancer Institute (U01 CA195547, K. Ness and M. Hudson, Principal Investigators; R01 CA157838, G. Armstrong, Principal Investigator), the Cancer Center Support (CORE) grant (P30 CA21765, C. Roberts, Principal Investigator), and the American Lebanese-Syrian Associated Charities (ALSAC).