Cardiovascular Family History Increases Risk for Late-Onset Adverse Cardiovascular Outcomes in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Report.

Background: Survivors of childhood cancer have an increased risk of therapy-related cardiovascular disease (CVD). It is not known whether family history (FH) of CVD further increases risk of adverse cardiovascular outcomes among survivors. Methods: Family history of CVD was collected from 1,260 survivors (median age at diagnosis 8 years [range 0-23], age at last follow-up 35 years [18-66]) of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with CVD (CTCAE grade 2-4 events) and cardiovascular risk factors. Results: Among survivors exposed to chest-directed radiation and/or anthracycline chemotherapy (n=824): 7% reported a first-degree FH of heart failure (HF), 19% myocardial infarction (MI), 11% stroke, 26% atherosclerotic disease (MI and/or stroke), 62% hypertension, and 31% diabetes mellitus (DM). 18% of exposed survivors developed HF, 9% MI, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% DM. Having a first-degree FH of atherosclerotic disease was independently associated with development of treatment-related HF (RR 1.38, 95%CI 1.01-1.88, p=0.04) among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree FH of hypertension (RR 1.55, 95%CI 1.26-1.92, p<0.0001) or of any cardiovascular disease (MI, stroke, or HF [RR 1.30, 95%CI 1.06-1.59, p=0.01]). Conclusion: Family history of CVD and cardiovascular risk factors independently increased risk of HF and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies. Impact: These data show the importance of cardiovascular FH as a risk factor for cardiovascular disease in survivors of childhood cancer.