Endothelial dysfunction in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort study.

Authors

null

Daniel A. Mulrooney

St. Jude Children's Research Hospital, Memphis, TN

Daniel A. Mulrooney , Kirsten K. Ness , Sujuan Huang , Aimee Santucci , Robert P. Hebbel , Anna S. Solovey , Daniel Duprez , Matthew J. Ehrhardt , Daniel M. Green , Deokumar Srivastava , Leslie L. Robison , Melissa M. Hudson

Organizations

St. Jude Children's Research Hospital, Memphis, TN, University of Minnesota, Minneapolis, MN

Research Funding

NIH

Background: Endothelial dysfunction, as an indicator of vascular disease in childhood cancer survivors (CCS) has not been widely studied. Methods: Markers of vascular inflammation (high sensitivity C-reactive protein [hsCRP]), hemostasis (fibrinogen), activation (endothelial cell expression of vascular cell adhesion molecule [VCAM-1]) and functional testing (large/small artery elasticity [L/SAE], pulse wave velocity [PWV]) were assessed in 200 CCS, ≥10 years from diagnosis, and 192 age/gender matched healthy controls. Exclusion criteria included: inflammatory processes, use of anti-inflammatory or cardiovascular medications, or pregnancy. Differences were assessed by adjusted multivariable linear regression. Results: CCS (53% male) of leukemia/lymphoma (59%), central nervous system tumors (6%), sarcomas (11.5%), embryonal tumors (22.5%), and other (1%) had a mean age at diagnosis 7.3 years (SD ±5.7). CCS and controls did not differ in current age (mean 34.1 ±9.2 vs. 33.5 years ±9.8), body mass index, smoking, mean systolic (124 mm Hg ±11.7 vs. 123 ±11.9) or diastolic blood pressure (73 ±9.5 vs. 71 ±9.5). Fasting low- (110 mg/dl ±31 vs. 102 ±30) and high-density (52 ±16 vs. 56 ±18) cholesterol levels differed between survivors and controls (p<0.01). Endothelial expression of VCAM-1 and PWV were statistically significantly increased in CCS; arterial elasticity was significantly reduced (table). Therapeutic exposures (anthracyclines and radiation) were not significantly associated with endothelial dysfunction. Conclusions: Childhood cancer survivors have greater endothelial dysfunction, a sign of atherosclerosis, and preventive measures should be investigated.

Vascular biomarkers and functional testing.

Survivors
Controls
P-value*
Mean(95%CI)Mean(95%CI)
Vascular Biomarkers
hsCRP (mg/L)1.5(1.1 – 2.0)1.3(1.0 – 1.8)0.36
Fibrinogen (mg/dl)166(147 – 184)182(163 – 201)0.06
Surface VCAM-1 (%)67(61 – 73)44(38 – 51)<0.01
Vascular Function
LAE (ml/mm Hg x 10)16.9(15.8 – 18.0)18.1(17.0 – 19.2)0.02
SAE (ml/mm Hg x 100)6.9(6.3 – 7.5)8.5(7.8 – 9.1)<0.01
PWV (m/s)7.1(6.8 – 7.3)6.5(6.2 – 6.8)<0.01

*adjusted for age, race, BMI, smoking, physical activity, education, employment

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Pediatric Oncology

Track

Pediatric Oncology

Sub Track

Survivorship

Citation

J Clin Oncol 35, 2017 (suppl; abstr 10564)

DOI

10.1200/JCO.2017.35.15_suppl.10564

Abstract #

10564

Poster Bd #

321

Abstract Disclosures