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
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.
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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