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

Gregory Armstrong, Kevin C. Oeffinger, Yan Chen, Toana Kawashima, Yutaka Yasui, Wendy Leisenring, Marilyn Stovall, Eric J. Chow, Charles A. Sklar, Daniel A. Mulrooney, Ann C. Mertens, William Border, Jean Bernard Durand, Leslie L. Robison, Lillian R. Meacham

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Abstract

Purpose: To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. Patients and Methods: 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. Results: 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 Ptrend < .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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)3673-3680
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number29
DOIs
StatePublished - Oct 10 2013

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Survivors
Hypertension
Cardiac Arrhythmias
Coronary Artery Disease
Heart Failure
Neoplasms
Siblings
Incidence
Dyslipidemias
Diabetes Mellitus
Radiotherapy
Thorax
Obesity
Cross-Sectional Studies
Heart Rate
Mortality
Therapeutics
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Armstrong, G., Oeffinger, K. C., Chen, Y., Kawashima, T., Yasui, Y., Leisenring, W., ... Meacham, L. R. (2013). Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. Journal of Clinical Oncology, 31(29), 3673-3680. https://doi.org/10.1200/JCO.2013.49.3205

Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. / Armstrong, Gregory; Oeffinger, Kevin C.; Chen, Yan; Kawashima, Toana; Yasui, Yutaka; Leisenring, Wendy; Stovall, Marilyn; Chow, Eric J.; Sklar, Charles A.; Mulrooney, Daniel A.; Mertens, Ann C.; Border, William; Durand, Jean Bernard; Robison, Leslie L.; Meacham, Lillian R.

In: Journal of Clinical Oncology, Vol. 31, No. 29, 10.10.2013, p. 3673-3680.

Research output: Contribution to journalArticle

Armstrong, G, Oeffinger, KC, Chen, Y, Kawashima, T, Yasui, Y, Leisenring, W, Stovall, M, Chow, EJ, Sklar, CA, Mulrooney, DA, Mertens, AC, Border, W, Durand, JB, Robison, LL & Meacham, LR 2013, 'Modifiable risk factors and major cardiac events among adult survivors of childhood cancer', Journal of Clinical Oncology, vol. 31, no. 29, pp. 3673-3680. https://doi.org/10.1200/JCO.2013.49.3205
Armstrong, Gregory ; Oeffinger, Kevin C. ; Chen, Yan ; Kawashima, Toana ; Yasui, Yutaka ; Leisenring, Wendy ; Stovall, Marilyn ; Chow, Eric J. ; Sklar, Charles A. ; Mulrooney, Daniel A. ; Mertens, Ann C. ; Border, William ; Durand, Jean Bernard ; Robison, Leslie L. ; Meacham, Lillian R. / Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 29. pp. 3673-3680.
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abstract = "Purpose: To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. Patients and Methods: 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. Results: 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 Ptrend < .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). Conclusion: 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.",
author = "Gregory Armstrong and Oeffinger, {Kevin C.} and Yan Chen and Toana Kawashima and Yutaka Yasui and Wendy Leisenring and Marilyn Stovall and Chow, {Eric J.} and Sklar, {Charles A.} and Mulrooney, {Daniel A.} and Mertens, {Ann C.} and William Border and Durand, {Jean Bernard} and Robison, {Leslie L.} and Meacham, {Lillian R.}",
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T1 - Modifiable risk factors and major cardiac events among adult survivors of childhood cancer

AU - Armstrong, Gregory

AU - Oeffinger, Kevin C.

AU - Chen, Yan

AU - Kawashima, Toana

AU - Yasui, Yutaka

AU - Leisenring, Wendy

AU - Stovall, Marilyn

AU - Chow, Eric J.

AU - Sklar, Charles A.

AU - Mulrooney, Daniel A.

AU - Mertens, Ann C.

AU - Border, William

AU - Durand, Jean Bernard

AU - Robison, Leslie L.

AU - Meacham, Lillian R.

PY - 2013/10/10

Y1 - 2013/10/10

N2 - Purpose: To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. Patients and Methods: 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. Results: 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 Ptrend < .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). Conclusion: 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.

AB - Purpose: To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. Patients and Methods: 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. Results: 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 Ptrend < .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). Conclusion: 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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