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Anthracycline Causes Impaired Vascular Endothelial Function and Aortic Stiffness in Long Term Survivors of Childhood Cancer

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Pathology & Oncology Research

Abstract

Vascular and endothelial functions were investigated in long term survivors of childhood cancer exposed to anthracycline treatment. We enrolled 96 long-term survivors (57 males and 39 females, mean age 14.9 ± 5.3 year) of different childhood cancers and 72 age-, sex-, bodyweight- and blood pressure matched controls (39 males and 33 females, mean age 13.7 ± 4.9 year). Aortic stiffness was characterized by echocardiography. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD%) and nitrate-mediated dilatation (NTG%). Results were compared between three subgroups: anthracycline treated, only chemotherapy treated and control subgroups. The cumulative anthracycline dose was less than 350 mg/m2. The healthy control subgroup had a significantly greater FMD response (13.13 ± 2.40 %), and lower stiffness index (2.08 ± 0.6) than both the anthracycline (7.12 ± 6.28 % and 6.45 ± 3.25, respectively) and only chemotherapy treated (10.17 ± 4.23 % and 4.12 ± 2.32, respectively) subgroups. In the anthracycline treated subgroup a significantly (p < 0.01) lower FMD% response, and higher stiffness index were detected than in the only chemotherapy treated subgroup. Higher triglyceride level, higher cumulative anthracycline dose and lower age at the start of treatment were found to be associated independently with impairment of FMD% response and aortic stiffness. We found a significant negative correlation between FMD and aortic stiffness (p < 0.001) and a positive correlation between FMD and distensibility (p < 0.0001) Childhood cancer long term survivors exposed to anthracycline treatment exhibit a marked preclinical vasculopathy, characterized by endothelial dysfunction and increased arterial stiffness, contributing to a deteriorated cardiovascular function.

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Acknowledgments

The help of Zsolt Karányi in performing statistical analysis is acknowledged. This work was supported by the grant of the Health Science Council of the Ministry of Education Republic of Hungary (ETT) No. 396/2006, 01-478/2009 and by the “For the leukemic children” foundations. The publication is supported by the TÁMOP 4.2.1./B-09/1/KONV-2010-0007 project. The project is co-financed by the European Union and the European Social Fund.

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Authors and Affiliations

  1. Department of Medicine, University of Debrecen Medical and Health Science Center, 4025, Nagyerdei krt. 98, Debrecen, Hungary

    Zoltan Jenei, Ágnes Horváth & György Paragh

  2. Department of Pediatric Hematology-Oncology, Medical and Health Science Center of University Debrecen, Debrecen, Hungary

    Edit Bárdi & Csongor Kiss

  3. Department of Neurology, Medical and Health Science Center of University Debrecen, Debrecen, Hungary

    Mária Tünde Magyar

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  1. Zoltan Jenei
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  2. Edit Bárdi
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  3. Mária Tünde Magyar
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  4. Ágnes Horváth
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  5. György Paragh
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  6. Csongor Kiss
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Correspondence to Zoltan Jenei.

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Zoltan Jenei and Edit Bárdi Equal opportunity first authors.

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Jenei, Z., Bárdi, E., Magyar, M.T. et al. Anthracycline Causes Impaired Vascular Endothelial Function and Aortic Stiffness in Long Term Survivors of Childhood Cancer. Pathol. Oncol. Res. 19, 375–383 (2013). https://doi.org/10.1007/s12253-012-9589-6

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  • DOI: https://doi.org/10.1007/s12253-012-9589-6

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