Vascular Assessment in Adult Survivors of Childhood Cancer: A St. Jude Lifetime Cohort Study Report

While end-organ toxicities following cancer therapy have been well described, long-term vascular health has received less attention.

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.

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.

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%).

CCSs have evidence of early vascular dysfunction, suggestive of premature atherogenesis.