Resting and exercise arterial dysfunction in anthracycline-treated adult survivors of childhood cancers

Abstract

Background: Emerging evidence suggests potential arterial damage with the use of anthracycline-basedchemotherapeutic regimens. We determined arterial function at rest and during exercise in anthracycline-treated adultsurvivors of childhood cancers.Methods: Ninety-six adult survivors (54 males) aged 25.0 ± 5.9 years and 60 (30 males) healthy controls were studied.Central systolic blood pressure (cSBP) and radial augmentation index (rAI) was determined by applanation tonometry.Carotid arterial stiffness and intima-media thickness (IMT) were assessed using high-resolution ultrasound.Results: At rest, survivors had significantly greater carotid IMT (p< 0.001) and stiffness index (p < 0.001), andhigher cSBP (p= 0.037), rAI (p= 0.004) and rAI adjusted for a heart rate of 75/min (p= 0.009) than controls. Atsubmaximal supine exercise testing, survivors had significantly greater percentage increase in carotid stiffnessthan controls (p< 0.001). Among survivors, 32 and 53% had respectively carotid IMT and exercise stiffnessindex exceeding normal (> + 2SD of controls). The slopes of increase in carotid IMT (p< 0.001) and exercise-inducedchanges in carotid stiffness (p< 0.001) with age were significantly greater in survivors than controls. Multivariateanalysis revealed carotid IMT (β=0.32,p< 0.001) to be an significant correlate of dynamic percentage increase instiffness index during exercise.Conclusions: Arterial dysfunction is evident at rest and worsens during exercise in anthracycline-treated adult survivorsof childhood cancers.