Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy

Steven E Lipshultz, David C. Landy, Gabriela Lopez-Mitnik, Stuart R. Lipsitz, Andrea S. Hinkle, Louis S. Constine, Carol A. French, Amy M. Rovitelli, Cindy Proukou, M. Jacob Adams, Tracie L Miller

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status. Methods: We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls. Results: The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons). Conclusion: Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.

Original languageEnglish
Pages (from-to)1050-1057
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number10
DOIs
StatePublished - Apr 1 2012

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Survivors
Neoplasms
Cardiovascular Abnormalities
Siblings
Therapeutics
Inflammation
Brain Natriuretic Peptide
Anthracyclines
C-Reactive Protein
Fasting
Survival Rate
Stroke
Myocardial Infarction
Guidelines
Insulin
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lipshultz, S. E., Landy, D. C., Lopez-Mitnik, G., Lipsitz, S. R., Hinkle, A. S., Constine, L. S., ... Miller, T. L. (2012). Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. Journal of Clinical Oncology, 30(10), 1050-1057. https://doi.org/10.1200/JCO.2010.33.7907

Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. / Lipshultz, Steven E; Landy, David C.; Lopez-Mitnik, Gabriela; Lipsitz, Stuart R.; Hinkle, Andrea S.; Constine, Louis S.; French, Carol A.; Rovitelli, Amy M.; Proukou, Cindy; Adams, M. Jacob; Miller, Tracie L.

In: Journal of Clinical Oncology, Vol. 30, No. 10, 01.04.2012, p. 1050-1057.

Research output: Contribution to journalArticle

Lipshultz, SE, Landy, DC, Lopez-Mitnik, G, Lipsitz, SR, Hinkle, AS, Constine, LS, French, CA, Rovitelli, AM, Proukou, C, Adams, MJ & Miller, TL 2012, 'Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy', Journal of Clinical Oncology, vol. 30, no. 10, pp. 1050-1057. https://doi.org/10.1200/JCO.2010.33.7907
Lipshultz SE, Landy DC, Lopez-Mitnik G, Lipsitz SR, Hinkle AS, Constine LS et al. Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. Journal of Clinical Oncology. 2012 Apr 1;30(10):1050-1057. https://doi.org/10.1200/JCO.2010.33.7907
Lipshultz, Steven E ; Landy, David C. ; Lopez-Mitnik, Gabriela ; Lipsitz, Stuart R. ; Hinkle, Andrea S. ; Constine, Louis S. ; French, Carol A. ; Rovitelli, Amy M. ; Proukou, Cindy ; Adams, M. Jacob ; Miller, Tracie L. / Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 10. pp. 1050-1057.
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abstract = "Purpose: To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status. Methods: We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls. Results: The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons). Conclusion: Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.",
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AU - Hinkle, Andrea S.

AU - Constine, Louis S.

AU - French, Carol A.

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N2 - Purpose: To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status. Methods: We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls. Results: The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons). Conclusion: Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.

AB - Purpose: To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status. Methods: We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls. Results: The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons). Conclusion: Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.

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