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-based chemotherapeutic regimens. We determined arterial function at rest and during exercise in anthracycline-treated adult survivors 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), and higher cSBP (p = 0.037), rAI (p = 0.004) and rAI adjusted for a heart rate of 75/min (p = 0.009) than controls. At submaximal supine exercise testing, survivors had significantly greater percentage increase in carotid stiffness than controls (p < 0.001). Among survivors, 32 and 53% had respectively carotid IMT and exercise stiffness index exceeding normal (> + 2SD of controls). The slopes of increase in carotid IMT (p < 0.001) and exercise-induced changes in carotid stiffness (p < 0.001) with age were significantly greater in survivors than controls. Multivariate analysis revealed carotid IMT (β = 0.32, p < 0.001) to be an significant correlate of dynamic percentage increase in stiffness index during exercise. Conclusions: Arterial dysfunction is evident at rest and worsens during exercise in anthracycline-treated adult survivors of childhood cancers.