P3447Multimodal assessment and phenomapping of early atherosclerosis in children with chronic disease
Authors: Ververs F A , Eikendal A L M , Westenberg J J M , Van Der Geest R J , Nuboer R , Wulffraat N M , Van Der Ent C K , Leiner T , Grotenhuis H B , Schipper H S 
Published: October 2019

Abstract

Background
Childhood survival of chronic disease steadily increased over the last decades. However, accumulating evidence suggests that survivors are at risk for early atherosclerosis. The “Cardiovascular Disease in Children with chronic disease” (CDC) study has two aims. First, multimodal assessment of early atherosclerosis was performed in adolescents with chronic inflammatory- and metabolic disorders in order to develop new diagnostic approaches. As fatty streak formation starts in the abdominal aorta, aortic wall thickness (AWT) and pulse wave velocity (PWV) were measured using cardiovascular magnetic resonance imaging (MRI), and compared with traditional carotid intima-media thickness (cIMT) and echocardiography. Second, comprehensive risk profiling was performed, including phenomapping of early risk factors, in order to establish cardiovascular risk profiles in childhood.

Methods
113 adolescents aged 12–19 years old were enrolled*. The study population includes adolescents with juvenile idiopathic arthritis (JIA, n=19), cystic fibrosis (CF, n=24), obesity (n=20), corrected coarctation of the aorta (CoA, n=25), and corrected atrial septal defect as control group (ASD, n=25). The aorta was imaged on a 3.0 Tesla MR system using the 3D-T1-BB-VISTA sequence. Aortic PWV was assessed using velocity-encoded MRI. cIMT was measured in three directions for both the right- and left carotid artery using echography. Unbiased hierarchical clustering was performed on phenotypic data (phenomapping), including anthropomorphic-, metabolic-, and inflammatory parameters.

Results*
Aortic pulse wave velocity on MRI was highest in the obese group compared to controls (p=0.002), yet JIA patients (p=0.015), CoA patients (p=0.029), and CF patients (p=0.044) also showed increased PWV compared to controls. Aortic wall thickness was highest in obese adolescents (p=0.020) and in CF patients (p=0.043). cIMT was only increased in CoA patients (p=0.000). While PWV and AWT showed correlation with inflammatory- and metabolic parameters such as lymphocyte count (PWV, p=0.043), monocyte count (PWV, p=0.002; AWT, p=0.036), CRP (AWT, p=0.032), and QUICKI (PWV, p=0.026), cIMT correlated with systolic blood pressure (p=0.017). Phenomapping of risk factors will further define distinct cardiovascular risk profiles*.

Conclusion
Multimodal assessment of early atherosclerosis in children with chronic disease reveals differential vascular changes. While traditional cIMT is associated with increased systolic blood pressure in young CoA patients, aortic PWV and aortic wall thickness reflect early systemic inflammatory- and metabolic derangement. Phenomapping traditional risk factors alongside inflammatory- and metabolic parameters bears promise to establish early cardiovascular risk profiles in childhood chronic disease*.
*Patient inclusion finishes May 2019, followed by phenomapping of patient characteristics. At the ESC, final data will be presented.

Acknowledgement/Funding
Wilhelmina Children's Hospital Research Fund, Dutch Topsector Life Sciences and Health TKI fund, Nutricia Research fund. HS was supported by VENI-NWO.