Rational: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study established that atherogenesis starts in childhood, initiating in the iliac arteries and abdominal aorta and subsequently develops in higher regions of the arterial tree. Childhood and adolescence thereby provide a unique window of opportunity to prevent atherosclerotic cardiovascular disease (ASCVD) later in life, especially for pediatric groups at risk. The growing list of pediatric groups at risk includes chronic inflammatory disorders, organ transplant recipients, familial hypercholesterolemia, endocrine disorders, childhood cancer survivors, chronic kidney diseases, congenital heart diseases, fetal growth restriction, and premature birth, next to increasing numbers of children and adolescents with traditional risk factors such as obesity, hypertension, hyperlipidemia, and hyperglycemia. The best way to assess cardiovascular health in the pediatric population is relatively unchartered territory. Multisite and multimodal assessment of early atherosclerosis emerged as the best way to capture the complexity of atherosclerosis as a systemic disease. Next to conventional carotid intima-media thickness measurements, implementation of aortic pulse wave velocity and endothelial function measurements can advance the assessment of early atherosclerosis in pediatrics.

Objective: The primary objective of this study is to establish the effect of disease and lifestyle associated cardiovascular risk factors on preclinical atherosclerosis in children with a chronic condition, and follow this up over time.

Study design: The SMART-Youth study is a prospective, longitudinal cohort study including children with various chronic conditions followed up in the Wilhelmina Children’s Hospital.

Study population: Children with various chronic conditions who are enrolled in the PROactive study, within the age range of 8-18 years. The study will include the following chronic conditions: cystic fibrosis, juvenile idiopathic arthritis, systemic autoimmune diseases, chronic kidney disease, primary immunodeficiency, autoinflammatory conditions, inflammatory bowel disease, and congenital heart disease, as well as children with a history of premature birth or fetal growth restriction, and children with persistent somatic symptoms. The total expected inclusion rate entails 1350 subjects within five years.

Main study parameters/endpoints: Carotid Intima Media Thickness (cIMT) and Aortic pulse wave velocity (PWV) as preclinical atherosclerosis outcomes.

R, 4.2