ON-LINE SUPPLEMENT Abnormal Central Pulsatile Hemodynamics in Adolescents with Obesity : Higher Aortic Forward Pressure Wave Amplitude is Independently Associated with Greater Left Ventricular Mass

Childhood obesity has increased dramatically in the United States during the past 30 years, which has been associated with a parallel rise in systolic blood pressure (BP) and pulse pressure (PP) in adolescents and young adults. Consistent with the elevation in systolic BP and PP, there has been an increase in the rates of prehypertension and hypertension mostly in youth with obesity, with the majority phenotype being in the form of isolated systolic, rather than, systolic/diastolic hypertension. Thus, these data suggest that the obesity-associated elevation in BP in youth may be related to abnormalities in structure and function of the large elastic arteries, rather than alterations in small resistance arteries and arterioles that govern peripheral vascular resistance and mean BP. Even in the absence of hypertension, however, obesity in children and adolescents is associated with elevated left ventricular (LV) mass and increased adiposity in youth predicts the excess LV mass in adulthood beyond what is expected for somatic growth. This is important because higher LV mass is a strong independent predictor of cardiovascular disease (CVD) morbidity and mortality in adults. In cross-sectional studies, higher body mass index (BMI) or weight are independent predictors of elevated LV mass in childhood in multiple regression models that include brachial systolic BP. In addition, longitudinal studies indicate that increased LV mass may precede the development of higher brachial systolic BP in obese youth. Therefore, these findings suggest that the LV hypertrophy in childhood and young adulthood attributed to excess childhood adiposity is not explained simply by higher brachial BP. Moreover, central systolic BP and PP are more closely associated with LV wall thickness than brachial BP in adults. However, whether central BP or related pulsatile hemodynamics contribute to LV hypertrophy rather than brachial measured BP in obese youth is unknown. Abstract—We hypothesized that increased aortic forward pressure wave amplitude (Pf), which is determined by characteristic impedance (Zc) in the proximal aorta, is the primary hemodynamic determinant of obesity-associated higher left ventricular (LV) mass in adolescents. Aortic pulsatile hemodynamics were measured noninvasively in 60 healthy adolescents (age 14–19 years; 42% male; 50% black) by sequential recordings of pulse waveforms via tonometry, brachial blood pressure, and pulsed Doppler and diameter of the LV outflow tract using 2-dimensional echocardiography. Adolescents who were overweight/obese (n=23; age 16.0±0.3 years; body mass index ≥85th percentile) had higher LV mass index, brachial and carotid systolic blood pressure and pulse pressure, normalized Zc and Pf compared with adolescents with healthy weight (n=37; 16.7±0.3 years; body mass index <85th percentile, all P<0.01). In contrast, there was no difference in mean or diastolic blood pressure, carotid-femoral pulse wave velocity, carotid augmentation index, or aortic backward wave amplitude (all P>0.05). Stepwise multiple linear regression analysis that included age, sex, race, normalized Zc, and brachial systolic blood pressure revealed that body mass index (B±SE; 0.49±0.20, P=0.02, R=0.26), aortic Pf (0.22±0.07; P<0.02, R change=0.11), and cardiac output (2.82±1.02, P<0.01; R change=0.08) were significant correlates of LV mass index (total R=0.44, P<0.01). These findings suggest that higher aortic Pf is a major hemodynamic determinant of increased LV mass in adolescents with elevated adiposity. Improper matching between aortic diameter and pulsatile flow during early systole potentially contributes to the early development of LV hypertrophy in childhood obesity. (Hypertension. 2016;68:12001207. DOI: 10.1161/HYPERTENSIONAHA.116.07918.) • Online Data Supplement