The Effect of Atorvastatin on Vascular Function and Structure in Young Adult Survivors of Childhood Cancer

A Randomized, Placebo-Controlled Pilot Clinical Trial

Kara L. Marlatt, Julia Steinberger, Kyle Rudser, Donald R Dengel, Karim T Sadak, Jill L. Lee, Anne H Blaes, Daniel A. Duprez, Joanna L. Perkins, Julie A. Ross, Aaron S Kelly

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Abstract

Many adult survivors of childhood cancer are at high-risk of developing cardiovascular disease. Cancer therapy may cause damage to the vascular endothelium, thereby initiating atherosclerosis. Atorvastatin has been shown to improve endothelial function independent of reducing cholesterol, as well as reduce/slow arterial stiffness and thickening, yet has never been studied in childhood cancer survivors (CCS). Methods: Twenty-seven young adult (age 26.8 ± 6.2 years) survivors of childhood acute lymphoblastic leukemia or Non-Hodgkin's lymphoma were randomly assigned (1:1) 40 mg/day of atorvastatin or placebo for 6 months. Brachial artery flow-mediated dilation (FMD), small artery reactive hyperemia index (RHI), arterial stiffness, and carotid artery elasticity/thickness were assessed. Results: Fifteen participants completed the trial. No significant treatment effect for any vascular outcomes was observed at 6 months; however, a significant decrease in peak FMD (-3.0 [95% confidence interval [CI]: -5.3, -0.7]) and a trending significant decrease in RHI (-0.3 [95% CI: -0.62, 0.01]) was observed in the placebo group, resulting in a trend toward a treatment effects (p < 0.10). No effect on arterial stiffness, carotid arterial elasticity, or thickness was observed. Conclusion: Six months of atorvastatin treatment did not improve endothelial function or arterial stiffness in young adult CCS. While a trend toward an improvement in endothelial function was present, findings should be interpreted with caution owing to the small number of evaluable participants and subsequent lack of sufficient power. Further research in a larger sample size is needed to fully elucidate the effects of atorvastatin on vascular function. Trial registered at clinicaltrials.gov as NCT01733953.

Original languageEnglish (US)
Pages (from-to)442-450
Number of pages9
JournalJournal of Adolescent and Young Adult Oncology
Volume8
Issue number4
DOIs
StatePublished - Aug 1 2019

Fingerprint

Vascular Stiffness
Controlled Clinical Trials
Blood Vessels
Young Adult
Placebos
Hyperemia
Elasticity
Dilatation
Neoplasms
Confidence Intervals
Brachial Artery
Vascular Endothelium
Therapeutics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Carotid Arteries
Sample Size
Non-Hodgkin's Lymphoma
Atherosclerosis
Cardiovascular Diseases
Arteries

Keywords

  • cardiovascular
  • statin
  • trial
  • vascular

Cite this

@article{ca1a9af5541a4627983505bd17072a71,
title = "The Effect of Atorvastatin on Vascular Function and Structure in Young Adult Survivors of Childhood Cancer: A Randomized, Placebo-Controlled Pilot Clinical Trial",
abstract = "Many adult survivors of childhood cancer are at high-risk of developing cardiovascular disease. Cancer therapy may cause damage to the vascular endothelium, thereby initiating atherosclerosis. Atorvastatin has been shown to improve endothelial function independent of reducing cholesterol, as well as reduce/slow arterial stiffness and thickening, yet has never been studied in childhood cancer survivors (CCS). Methods: Twenty-seven young adult (age 26.8 ± 6.2 years) survivors of childhood acute lymphoblastic leukemia or Non-Hodgkin's lymphoma were randomly assigned (1:1) 40 mg/day of atorvastatin or placebo for 6 months. Brachial artery flow-mediated dilation (FMD), small artery reactive hyperemia index (RHI), arterial stiffness, and carotid artery elasticity/thickness were assessed. Results: Fifteen participants completed the trial. No significant treatment effect for any vascular outcomes was observed at 6 months; however, a significant decrease in peak FMD (-3.0 [95{\%} confidence interval [CI]: -5.3, -0.7]) and a trending significant decrease in RHI (-0.3 [95{\%} CI: -0.62, 0.01]) was observed in the placebo group, resulting in a trend toward a treatment effects (p < 0.10). No effect on arterial stiffness, carotid arterial elasticity, or thickness was observed. Conclusion: Six months of atorvastatin treatment did not improve endothelial function or arterial stiffness in young adult CCS. While a trend toward an improvement in endothelial function was present, findings should be interpreted with caution owing to the small number of evaluable participants and subsequent lack of sufficient power. Further research in a larger sample size is needed to fully elucidate the effects of atorvastatin on vascular function. Trial registered at clinicaltrials.gov as NCT01733953.",
keywords = "cardiovascular, statin, trial, vascular",
author = "Marlatt, {Kara L.} and Julia Steinberger and Kyle Rudser and Dengel, {Donald R} and Sadak, {Karim T} and Lee, {Jill L.} and Blaes, {Anne H} and Duprez, {Daniel A.} and Perkins, {Joanna L.} and Ross, {Julie A.} and Kelly, {Aaron S}",
year = "2019",
month = "8",
day = "1",
doi = "10.1089/jayao.2017.0075",
language = "English (US)",
volume = "8",
pages = "442--450",
journal = "Journal of Adolescent and Young Adult Oncology",
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TY - JOUR

T1 - The Effect of Atorvastatin on Vascular Function and Structure in Young Adult Survivors of Childhood Cancer

T2 - A Randomized, Placebo-Controlled Pilot Clinical Trial

AU - Marlatt, Kara L.

AU - Steinberger, Julia

AU - Rudser, Kyle

AU - Dengel, Donald R

AU - Sadak, Karim T

AU - Lee, Jill L.

AU - Blaes, Anne H

AU - Duprez, Daniel A.

AU - Perkins, Joanna L.

AU - Ross, Julie A.

AU - Kelly, Aaron S

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Many adult survivors of childhood cancer are at high-risk of developing cardiovascular disease. Cancer therapy may cause damage to the vascular endothelium, thereby initiating atherosclerosis. Atorvastatin has been shown to improve endothelial function independent of reducing cholesterol, as well as reduce/slow arterial stiffness and thickening, yet has never been studied in childhood cancer survivors (CCS). Methods: Twenty-seven young adult (age 26.8 ± 6.2 years) survivors of childhood acute lymphoblastic leukemia or Non-Hodgkin's lymphoma were randomly assigned (1:1) 40 mg/day of atorvastatin or placebo for 6 months. Brachial artery flow-mediated dilation (FMD), small artery reactive hyperemia index (RHI), arterial stiffness, and carotid artery elasticity/thickness were assessed. Results: Fifteen participants completed the trial. No significant treatment effect for any vascular outcomes was observed at 6 months; however, a significant decrease in peak FMD (-3.0 [95% confidence interval [CI]: -5.3, -0.7]) and a trending significant decrease in RHI (-0.3 [95% CI: -0.62, 0.01]) was observed in the placebo group, resulting in a trend toward a treatment effects (p < 0.10). No effect on arterial stiffness, carotid arterial elasticity, or thickness was observed. Conclusion: Six months of atorvastatin treatment did not improve endothelial function or arterial stiffness in young adult CCS. While a trend toward an improvement in endothelial function was present, findings should be interpreted with caution owing to the small number of evaluable participants and subsequent lack of sufficient power. Further research in a larger sample size is needed to fully elucidate the effects of atorvastatin on vascular function. Trial registered at clinicaltrials.gov as NCT01733953.

AB - Many adult survivors of childhood cancer are at high-risk of developing cardiovascular disease. Cancer therapy may cause damage to the vascular endothelium, thereby initiating atherosclerosis. Atorvastatin has been shown to improve endothelial function independent of reducing cholesterol, as well as reduce/slow arterial stiffness and thickening, yet has never been studied in childhood cancer survivors (CCS). Methods: Twenty-seven young adult (age 26.8 ± 6.2 years) survivors of childhood acute lymphoblastic leukemia or Non-Hodgkin's lymphoma were randomly assigned (1:1) 40 mg/day of atorvastatin or placebo for 6 months. Brachial artery flow-mediated dilation (FMD), small artery reactive hyperemia index (RHI), arterial stiffness, and carotid artery elasticity/thickness were assessed. Results: Fifteen participants completed the trial. No significant treatment effect for any vascular outcomes was observed at 6 months; however, a significant decrease in peak FMD (-3.0 [95% confidence interval [CI]: -5.3, -0.7]) and a trending significant decrease in RHI (-0.3 [95% CI: -0.62, 0.01]) was observed in the placebo group, resulting in a trend toward a treatment effects (p < 0.10). No effect on arterial stiffness, carotid arterial elasticity, or thickness was observed. Conclusion: Six months of atorvastatin treatment did not improve endothelial function or arterial stiffness in young adult CCS. While a trend toward an improvement in endothelial function was present, findings should be interpreted with caution owing to the small number of evaluable participants and subsequent lack of sufficient power. Further research in a larger sample size is needed to fully elucidate the effects of atorvastatin on vascular function. Trial registered at clinicaltrials.gov as NCT01733953.

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KW - statin

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DO - 10.1089/jayao.2017.0075

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