Cross-Sectional Study of Arterial Stiffness in Adolescents with Down Syndrome

Abstract

Objectives: To test whether youth with Down syndrome have aortic stiffness indices, as measured by pulse wave velocity (PWV), that differ from youth without Down syndrome and to compare reference-based age-adjusted (age-PWV-Z) and height-adjusted (Ht-PWV-Z) in youth with and without Down syndrome.

Study design: Cross-sectional study of PWV in 129 adolescents with Down syndrome and 97 youth of comparable age, sex, race/ethnicity, and body mass index (BMI). PWV, age-PWV-Z, and Ht-PWV-Z were compared. Regression models were developed to test for associations with PWV.

Results: Youth with Down syndrome and controls were comparable in BMI-Z (1.4 [-1.5 to 2.8] vs 1.2 [-2.0 to 2.8], P = .57) but not Ht-Z (-2.3 [-4.7 to 0.8] vs 0.4 [-2.0 to 2.6], P < .0001). PWV (m/s, 5.0 [3.1-7.9] vs 5.0 [3.6-8.0], P = .5) and mean arterial pressure (MAP, mm Hg) (78 [61-102] vs 74 [64-97], P = .09) were not different between groups. In adjusted analyses confined to Down syndrome, PWV was associated only with BMI, but not age, black race, or MAP (R2 = 0.11). In contrast, BMI, age, black race, and MAP were all positively associated with and better explained PWV in controls (R2 = 0.50). PWV was not associated with height in youth with or without Down syndrome. Although age-PWV-Z was not different in Down syndrome (-0.36 [-2.93 to 3.49]) vs -0.15 [-2.32 to 3.22]), Ht-PWV-Z was greater in Down syndrome (0.32 [-2.28 to 4.07] vs -0.08 [-2.64 to 2.64], P = .002), and Ht-PWV-Z was greater than age-PWV-Z in Down syndrome (P < .0001).

Conclusions: The lack of relationship of PWV, an independent predictor of adult cardiovascular events, with its traditional determinants including MAP suggests Down syndrome-specific phenomena may alter such relationships in this population. In youth with Down syndrome, Ht-adjusted PWV may overestimate aortic stiffness.

Trial registration: Clinicaltrials.gov: NCT01821300.

Keywords: Down syndrome; cardiovascular disease; obesity; pulse-wave velocity.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

FIGURE 1.. Relationships of PWV to Potential Determinants of PWV in Adolescents with Down Syndrome (X) and Typically Developing Matched-Controls (•).

PWV more strongly correlated with A. age (nonDS: rho=0.36, p=0.0005 vs DS: rho=0.18, p=0.05), B. BMI (nonDS: rho=0.45, p<0.0001 vs DS: rho=0.28, p=0.002), and C. MAP in controls (nonDS: rho=0.36, p=0.005; DS: rho=0.16, p=0.07) compared with adolescents with DS. PWV did not correlate with height in either group (nonDS: rho=0.16, p=0.14; DS: rho=0.12, p=0.19). Fitted lines for DS (--) and controls (--) are also shown.

FIGURE 2.. Relationships of Height-Adjusted-PWV to Height-Z in Adolescents with Down Syndrome (X) and Typically Developing Matched-Controls (•).

Height-adjusted PWV-Z was higher in DS (p=0.012) vs controls. Height-adjusted PWV-Z was negatively correlated with Height-Z in both DS (rho=−0.35, p=0.0001) and controls (rho=−0.34, p=0.0006). Height was significantly lower in DS vs controls (inset, p

FIGURE 3, ONLINE.

In adolescents with DS, PWV did not differ by congenital heart defect status (• none, + present but not surgically managed, or X surgically-repaired, p=0.27). Surgically managed CHD included PDA, Atrial Septal Defect, Ventricular Septal Defect, Complete Atrioventricular Canal Defect; CHD nor managed with surgery included PDA, Atrial Septal Defect, Ventricular Septal Defect, bicuspid aortic valve.

FIGURE 4, ONLINE.. Comparison of Height-Adjusted-PWV and Age-Adjusted-PWV in Adolescents with Down Syndrome (X) and Typically Developing Matched-Controls (•).

Age-adjusted PWV-Z were not different in DS vs nonDS controls, (p=0.15). However, Height-adjusted PWV-Z was higher in DS (p=0.012) vs controls, and Height-adjusted PWV-Z was higher than Age-adjusted PWV-Z in DS (p