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 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.