Arterial stiffness and aortic hemodynamics as predictors for new or worsening cardiovascular events in childhood cancer survivors: A report from the St. Jude lifetime cohort.

Abstract

e24006 Background: Survival following childhood cancer has improved due to advances in treatment and supportive care. However, survivors are at high risk of cardiovascular diseases (CVDs) later in life. Aortic artery stiffening, captured by measuring the speed and magnitude of forward and reflected pulse waves, is an independent predictor of CVD and mortality in the general population. Methods: We evaluated associations between vascular function and new or worsening CVDs [coronary artery disease (CAD), cardiomyopathy, and hypertension (HTN)] among a subset (n = 249) of St. Jude Lifetime Cohort (SJLIFE) participants who had baseline vascular function assessment and returned for a standard follow up study visit (mean age at baseline (years) ± standard deviation: 34 ± 9 years, follow-up: 39 ± 9 years). CVD conditions were graded (dichotomized as grades 0-1 and 2-4) using the Common Terminology Criteria for Adverse Events (CTCAE). Aortic stiffness, brachial and aortic blood pressure (BP), and aortic wave reflection (augmented pressure, augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (AIx75), time and magnitude of the forward and reflected waves) were assessed using wave separation analyses. T-tests were used to test mean values between the groups with higher (2-5) and lower (0-1) grades. These tests informed the selection of identified variables for multivariate logistic models, which were adjusted for age, sex, race, body mass index, physical activity, smoking status, drinking behavior and vasoactive medications. Results: Most participants had a history of Hodgkin lymphoma (53.8%) or leukemia (20.5%) and 25.7% other diagnoses. There were 169 (67.9%) participants who had cranial/neck radiation, 167 (67.9%) received anthracyclines, and 150 (60.2%) alkylating agents. At baseline 38.2% had ≥grade 2 HTN, 9.2% cardiomyopathy, and 4% CAD. Having ≥ grade 2 CVDs was significantly associated with augmented markers of brachial and aortic BP, arterial stiffness, and wave reflection. Regression analyses revealed that AIx75 ≥ 17% was associated with an increased risk of new or worsening HTN (odds ratio (OR) 3.29, 95% confidence interval (CI) 1.03-10.48) and new or worsening cardiomyopathy (OR 4.06, 95% CI 1.02-16.16) an average of 5 years after baseline vascular testing. Conclusions: Childhood cancer survivors diagnosed with grades 2-4 CVDs at a baseline visit had elevated aortic stiffness and augmented indices of wave reflection compared to those with < grade 2 CVDs. Elevated AIx75 was associated with new or worsening HTN and cardiomyopathy five years later. Early detection and treatment of vascular dysfunction may ameliorate CVD late effects in childhood cancer survivors.