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J Clin Oncol. 2013 Oct 10;31(29):3673-80. doi: 10.1200/JCO.2013.49.3205. Epub 2013 Sep 3.

Modifiable risk factors and major cardiac events among adult survivors of childhood cancer.

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Gregory T. Armstrong, Daniel A. Mulrooney, and Leslie L. Robison, St. Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY; Yan Chen and Yutaka Yasui, University of Alberta, Edmonton, Alberta, Canada; Toana Kawashima, Wendy Leisenring, and Eric J. Chow, Fred Hutchinson Cancer Research Center; Eric J. Chow, Seattle Children's Hospital, Seattle, WA; Marilyn Stovall and Jean-Bernard Durand, The University of Texas MD Anderson Cancer Center, Houston, TX; and Ann C. Mertens, William Border, and Lillian R. Meacham, Emory University, Atlanta, GA.



To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer.


Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models.


Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all P(trend) < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7).


Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.

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