Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease

Abstract

Background Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that atherogenesis starts in the aorta, the CDACD (Cardiovascular Disease in Adolescents with Chronic Disease) study investigated preclinical aortic atherosclerosis in these adolescents. Methods and Results The cross-sectional CDACD study enrolled 114 adolescents 12 to 18 years old with chronic disorders including juvenile idiopathic arthritis, cystic fibrosis, obesity, corrected coarctation of the aorta, and healthy controls with a corrected atrial septal defect. Cardiovascular magnetic resonance was used to assess aortic pulse wave velocity and aortic wall thickness, as established aortic measures of preclinical atherosclerosis. Cardiovascular magnetic resonance showed a higher aortic pulse wave velocity, which reflects aortic stiffness, and higher aortic wall thickness in all adolescent chronic disease groups, compared with controls (P<0.05). Age (β=0.253), heart rate (β=0.236), systolic blood pressure (β=-0.264), and diastolic blood pressure (β=0.365) were identified as significant predictors for aortic pulse wave velocity, using multivariable linear regression analysis. Aortic wall thickness was predicted by body mass index (β=0.248) and fasting glucose (β=0.242), next to aortic lumen area (β=0.340). Carotid intima-media thickness was assessed using ultrasonography, and was only higher in adolescents with coarctation of the aorta, compared with controls (P<0.001). Conclusions Adolescents with chronic disease showed enhanced aortic stiffness and wall thickness compared with controls. The enhanced aortic pulse wave velocity and aortic wall thickness in adolescents with chronic disease could indicate accelerated atherogenesis. Our findings underscore the importance of the aorta for assessment of early atherosclerosis, and the need for tailored cardiovascular follow-up of children with chronic disease.

Keywords: CMR; adolescents; atherosclerosis; cIMT; children; chronic disease.

Figure 1. Arterial measures of preclinical atherosclerosis in adolescents with chronic disease

CMR‐assessment of aortic pulse wave velocity (A) and aortic wall thickness (B), compared with conventional ultrasonography assessment of cIMT (C) of adolescents with chronic disease (red dots) and healthy ASD controls (gray dots). Analyses were corrected for multiple testing. ASD indicates corrected atrial septal defect (controls); CF, cystic fibrosis; cIMT, carotid intima‐media thickness; CoA, corrected coarctation of the aorta; JIA, juvenile idiopathic arthritis; and OB, obesity. *P<0.05, **P<0.01, ***P<0.001.

Figure 2. Measures of preclinical atherosclerosis in adolescents with chronic disease

Summary of the CDACD study findings following CMR assessment of aortic pulse wave velocity and aortic wall thickness, next to conventional carotid intima‐media thickness measurements using ultrasonography, in adolescents with chronic disease. Upward arrows (↑) indicate an increase compared with the healthy controls and hyphens (–) indicate no difference. CDACD indicates Cardiovascular Disease in Adolescents with Chronic Disease study; CFTR, cystic fibrosis transmembrane conductance regulator protein; cIMT, carotid intima‐media thickness; and CMR, cardiovascular magnetic resonance imaging.