Clinical Assessment and Targeted Imaging to Characterize High-Risk Atherosclerotic Cardiovascular Disease of Survivors in SJLIFE

Overview

Childhood cancer survivors are at increased risk for premature atherosclerotic cardiovascular disease (ASCVD) due to cancer treatment-related exposures, including radiation therapy and platinum-based chemotherapy. Current ASCVD risk assessment tools may underestimate cardiovascular risk in younger survivors. This observational study performs detailed cardiovascular phenotyping using imaging, blood-based biomarkers, and vascular function testing among adult survivors enrolled in the St. Jude Lifetime Cohort (SJLIFE), with comparison to community controls, to better characterize subclinical ASCVD risk and inform survivor-specific prevention strategies. Primary Objective: Perform deeper phenotyping of SJLIFE participants at treatment-related risk of atherosclerotic cardiovascular disease \[ASCVD\] to facilitate early detection of pathophysiological targets appropriate for remediation. Secondary Objectives: Determine the distribution of lipoprotein (a) levels and prevalence of elevated levels among survivors with any treatment related exposure-based risk for ASCVD overall and then compared to community controls. Evaluate prevalence of clinical and imaging markers of ASCVD risk among survivors exposed only to platinum chemotherapy and compare that to community controls.

Survivors of childhood cancer experience substantially increased risk of ischemic heart disease and stroke compared to the general population. This excess risk is largely driven by cancer therapy exposures such as chest or neck radiation and platinum-based chemotherapy. However, most evidence-based ASCVD screening and prevention guidelines are derived from populations aged 40 years or older without cancer therapy exposure, leaving younger survivors inadequately risk stratified. This study leverages the St. Jude Lifetime Cohort (SJLIFE) to conduct enhanced cardiovascular phenotyping among survivors at treatment-related risk for ASCVD. Participants undergo coronary artery calcium (CAC) scoring using low-dose non-contrast ECG-gated CT, bilateral carotid ultrasound to assess carotid stenosis and intima-media thickness, blood-based measurement of lipoprotein(a), and noninvasive vascular function testing including pulse wave velocity, augmentation index, and arterial elasticity. A cohort of community control participants enrolled in SJLIFE undergoes identical testing. The primary objectives are to determine the prevalence of abnormal CAC and carotid stenosis among at-risk survivors and to compare findings with community controls. Secondary objectives include characterization of lipoprotein(a) levels and assessment of ASCVD markers among survivors exposed solely to platinum chemotherapy. The study uses a cross-sectional design with prospective longitudinal follow-up through ongoing participation in SJLIFE. Results are intended to inform future survivor-specific screening approaches and interventional trials.