PT  - JOURNAL ARTICLE
AU  - Goldberg, Jason F.
AU  - Ness, Kirsten K.
AU  - Chi, Xiaofei
AU  - Santucci, Aimee K.
AU  - Plana, Juan Carlos
AU  - Joshi, Vijaya M.
AU  - Luepker, Russell V.
AU  - Durand, Jean-Bernard
AU  - Partin, Robyn E.
AU  - Howell, Rebecca M.
AU  - Wilson, Carmen L.
AU  - Towbin, Jeffrey A.
AU  - Jefferies, John L.
AU  - Srivastava, Deo Kumar
AU  - Hudson, Melissa M.
AU  - Robison, Leslie L.
AU  - Armstrong, Gregory T.
TI  - Cardiovascular Family History Increases Risk for Late-Onset Adverse Cardiovascular Outcomes in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Report
AID  - 10.1158/1055-9965.EPI-20-0809
DP  - 2020 Oct 08
TA  - Cancer Epidemiology Biomarkers & Prevention
4099  - http://cebp.aacrjournals.org/content/early/2020/11/02/1055-9965.EPI-20-0809.short
4100  - http://cebp.aacrjournals.org/content/early/2020/11/02/1055-9965.EPI-20-0809.full
AB  - Background: Survivors of childhood cancer have an increased risk of therapy-related cardiovascular disease. It is not known whether family history of cardiovascular disease further increases risk of adverse cardiovascular outcomes among survivors.Methods: Family history of cardiovascular disease was collected from 1,260 survivors [median age at diagnosis, 8 years (range, 0–23); age at last follow-up, 35 years (range, 18–66)] of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with cardiovascular disease (Common Terminology Criteria for Adverse Events 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 family history of heart failure, 19% myocardial infarction, 11% stroke, 26% atherosclerotic disease (myocardial infarction and/or stroke), 62% hypertension, and 31% diabetes mellitus. Eighteen percent of exposed survivors developed heart failure, 9% myocardial infarction, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% diabetes mellitus. Having a first-degree family history of atherosclerotic disease was independently associated with development of treatment-related heart failure [RR, 1.38; 95% confidence interval (CI), 1.01–1.88; P = 0.04] among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree family history of hypertension (RR, 1.55; 95% CI, 1.26–1.92; P < 0.0001) or of any cardiovascular disease [myocardial infarction, stroke, or heart failure (RR, 1.30; 95% CI, 1.06–1.59; P = 0.01)].Conclusions: Family history of cardiovascular disease and cardiovascular risk factors independently increased risk of heart failure and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies.Impact: These data show the importance of cardiovascular family history as a risk factor for cardiovascular disease in survivors of childhood cancer.