Vascular Assessment in Adult Survivors of Childhood Cancer

Background: While end-organ toxicities following cancer therapy have been well described, long-term vascular health has received less attention. Objectives: The purpose of this study was to evaluate vascular health in childhood cancer survivors (CCSs) utilizing established and novel biomarkers and m...

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Main Authors: Amy M. Berkman, MD, Mingjuan Wang, MS, Aimee Santucci, PhD, Daniel Duprez, MD, PhD, Anna N. Solovey, MD, PhD, Deokumar Srivastava, PhD, Vijaya M. Joshi, MD, Daniel M. Green, MD, Leslie L. Robison, PhD, Kirsten K. Ness, PT, PhD, Melissa M. Hudson, MD, Daniel A. Mulrooney, MD, MS
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:JACC: Advances
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772963X25002388
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author Amy M. Berkman, MD
Mingjuan Wang, MS
Aimee Santucci, PhD
Daniel Duprez, MD, PhD
Anna N. Solovey, MD, PhD
Deokumar Srivastava, PhD
Vijaya M. Joshi, MD
Daniel M. Green, MD
Leslie L. Robison, PhD
Kirsten K. Ness, PT, PhD
Melissa M. Hudson, MD
Daniel A. Mulrooney, MD, MS
author_facet Amy M. Berkman, MD
Mingjuan Wang, MS
Aimee Santucci, PhD
Daniel Duprez, MD, PhD
Anna N. Solovey, MD, PhD
Deokumar Srivastava, PhD
Vijaya M. Joshi, MD
Daniel M. Green, MD
Leslie L. Robison, PhD
Kirsten K. Ness, PT, PhD
Melissa M. Hudson, MD
Daniel A. Mulrooney, MD, MS
author_sort Amy M. Berkman, MD
collection DOAJ
description Background: While end-organ toxicities following cancer therapy have been well described, long-term vascular health has received less attention. Objectives: The purpose of this study was to evaluate vascular health in childhood cancer survivors (CCSs) utilizing established and novel biomarkers and measures of arterial function. Methods: Serum biomarkers of inflammation (high-sensitivity C-reactive protein), hemostasis (fibrinogen, D-dimer, plasminogen activator inhibitor-1, tissue type plasminogen activator, von-Willebrand factor), and vasoregulation (surface and soluble vascular cell adhesion molecule-1 and P-selectin) were measured in this cross-sectional cohort study. Large and small arterial elasticity, pulse wave velocity, and augmentation index (AIx) were assessed. Differences between CCSs and sex- and age-matched controls were assessed in multivariable general linear regression models, adjusted for body mass index, race and ethnicity, smoking, and physical activity. Results: Among 200 CCSs (median time from diagnosis 26.3 years [range: 11.2-47.9 years], current age 33.5 years [range: 19.3-61.6 years]) and 192 controls (33.3 years [range: 18.3-60.3 years]), plasminogen activator inhibitor-1 (1,804.7 pg/mL vs 1,577.9 pg/mL, P = 0.007) and endothelial surface expression of vascular cell adhesion molecule-1 (67.6% vs 43.5%; P < 0.001) and P-selectin (65.7% vs 45.9%; P < 0.001) were significantly elevated in CCSs compared to controls. Large artery elasticity (16.8 mL/mm Hg × 10 vs 18.1 mL/mm Hg × 10; P = 0.013) and small artery elasticity (7.1 mL/mm Hg × 100 vs 8.7 mL/mm Hg × 100; P < 0.001) were reduced, while pulse wave velocity (6.8 m/s vs 6.3 m/s; P < 0.001) and AIx (13.3% vs 8.1%; P < 0.001) were significantly elevated. AIx was higher among survivors exposed to chest radiation (15.4%) compared to those not exposed (11.2%). Conclusions: CCSs have evidence of early vascular dysfunction, suggestive of premature atherogenesis.
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spelling doaj-art-d8d4535282684a6dba13d2fcecdc95ec2025-08-20T02:01:06ZengElsevierJACC: Advances2772-963X2025-06-014610182010.1016/j.jacadv.2025.101820Vascular Assessment in Adult Survivors of Childhood CancerAmy M. Berkman, MD0Mingjuan Wang, MS1Aimee Santucci, PhD2Daniel Duprez, MD, PhD3Anna N. Solovey, MD, PhD4Deokumar Srivastava, PhD5Vijaya M. Joshi, MD6Daniel M. Green, MD7Leslie L. Robison, PhD8Kirsten K. Ness, PT, PhD9Melissa M. Hudson, MD10Daniel A. Mulrooney, MD, MS11Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USADepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USADepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USACardiovascular Division, Department of Medicine, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USADivision of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USADepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USADepartment of Pediatrics and Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee, USADepartment of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USADepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USADepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USADepartment of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USADepartment of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Department of Pediatrics and Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee, USA; Address for correspondence: Dr Daniel A. Mulrooney, Division of Cancer Survivorship, Department of Oncology, St. Jude Children's Research Hospital, MS 735, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.Background: While end-organ toxicities following cancer therapy have been well described, long-term vascular health has received less attention. Objectives: The purpose of this study was to evaluate vascular health in childhood cancer survivors (CCSs) utilizing established and novel biomarkers and measures of arterial function. Methods: Serum biomarkers of inflammation (high-sensitivity C-reactive protein), hemostasis (fibrinogen, D-dimer, plasminogen activator inhibitor-1, tissue type plasminogen activator, von-Willebrand factor), and vasoregulation (surface and soluble vascular cell adhesion molecule-1 and P-selectin) were measured in this cross-sectional cohort study. Large and small arterial elasticity, pulse wave velocity, and augmentation index (AIx) were assessed. Differences between CCSs and sex- and age-matched controls were assessed in multivariable general linear regression models, adjusted for body mass index, race and ethnicity, smoking, and physical activity. Results: Among 200 CCSs (median time from diagnosis 26.3 years [range: 11.2-47.9 years], current age 33.5 years [range: 19.3-61.6 years]) and 192 controls (33.3 years [range: 18.3-60.3 years]), plasminogen activator inhibitor-1 (1,804.7 pg/mL vs 1,577.9 pg/mL, P = 0.007) and endothelial surface expression of vascular cell adhesion molecule-1 (67.6% vs 43.5%; P < 0.001) and P-selectin (65.7% vs 45.9%; P < 0.001) were significantly elevated in CCSs compared to controls. Large artery elasticity (16.8 mL/mm Hg × 10 vs 18.1 mL/mm Hg × 10; P = 0.013) and small artery elasticity (7.1 mL/mm Hg × 100 vs 8.7 mL/mm Hg × 100; P < 0.001) were reduced, while pulse wave velocity (6.8 m/s vs 6.3 m/s; P < 0.001) and AIx (13.3% vs 8.1%; P < 0.001) were significantly elevated. AIx was higher among survivors exposed to chest radiation (15.4%) compared to those not exposed (11.2%). Conclusions: CCSs have evidence of early vascular dysfunction, suggestive of premature atherogenesis.http://www.sciencedirect.com/science/article/pii/S2772963X25002388atherogenesischildhood cancer survivorsendothelial dysfunctionvascular dysfunction
spellingShingle Amy M. Berkman, MD
Mingjuan Wang, MS
Aimee Santucci, PhD
Daniel Duprez, MD, PhD
Anna N. Solovey, MD, PhD
Deokumar Srivastava, PhD
Vijaya M. Joshi, MD
Daniel M. Green, MD
Leslie L. Robison, PhD
Kirsten K. Ness, PT, PhD
Melissa M. Hudson, MD
Daniel A. Mulrooney, MD, MS
Vascular Assessment in Adult Survivors of Childhood Cancer
JACC: Advances
atherogenesis
childhood cancer survivors
endothelial dysfunction
vascular dysfunction
title Vascular Assessment in Adult Survivors of Childhood Cancer
title_full Vascular Assessment in Adult Survivors of Childhood Cancer
title_fullStr Vascular Assessment in Adult Survivors of Childhood Cancer
title_full_unstemmed Vascular Assessment in Adult Survivors of Childhood Cancer
title_short Vascular Assessment in Adult Survivors of Childhood Cancer
title_sort vascular assessment in adult survivors of childhood cancer
topic atherogenesis
childhood cancer survivors
endothelial dysfunction
vascular dysfunction
url http://www.sciencedirect.com/science/article/pii/S2772963X25002388
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