LAUSR

It is now recognized that primary hypertension is detectable in childhood. Life-course data on blood pressure (BP) trajectories from childhood to young adulthood indicate that a hypertensive pathway can be underway in late childhood. As shown in this Figure from Theodore et al the trajectories begin to separate by approximately age 11 years and children with higher BP follow a course toward hypertension in young adulthood. This trajectory is commonly associated with obesity along with obesity-associated metabolic abnormalities. Thus, children with primary hypertension and obesity can have lipid and other metabolic alterations that are similar to older adults with primary hypertension. Unlike adults with primary hypertension, the vascular system of children is more elastic, indicating that circulatory hemodynamics would be different in hypertensive children compared with hypertensive adults. The initiating mechanisms of childhood hypertension are not well understood. Earlier studies have demonstrated a hemodynamic profile of high cardiac output with normal peripheral resistance in an early phase of elevated BP, designated borderline hypertension. In young adulthood, this condition was mediated by heightened adrenergic activity. In later adulthood, hypertensive hemodynamics shift to an age-related decrease in cardiac output that is matched by an increase in peripheral resistance. The concept of a hyperkinetic circulatory condition fits with obesity-associated hypertension in childhood, wherein childhood obesity is considered to be associated with heightened sympathetic nervous system activity. The concept of a hyperkinetic state in youth is challenged in a publication in this issue by Park et al. These authors investigated participants in the ALSPAC (Avon Longitudinal Study of Parents and Children), a cohort investigated prospectively since age 7 years of age. At age 17 years a representative sample (N=2110) from the ALSPAC cohort had an echocardiogram, to quantify cardiac structure and function, in addition to measurements of BP, anthropometrics, and lifestyle behaviors. Based on measured cardiac output and mean arterial pressure (MAP), stroke volume and total peripheral resistance (TPR) were calculated. The sample was then stratified to quintals based on MAP and also stratified based on quintiles of left ventricular mass index. The higher quintiles of MAP were associated with higher stroke volume, higher heart rate, and higher TPR. The striking finding is that the relative contribution of stroke volume, heart rate, and TPR to MAP (and to systolic BP) was similar across all BP quintiles. Thus, in this population sample of adolescents at age 17 years, higher BP is because of both higher cardiac output and higher TPR and is not because of a high cardiac output with normal TPR. Multiple regression analysis on determinants of left ventricular mass index confirmed a significant association of TPR, as well as measures of cardiac output. These findings on the increase in TPR in an early phase of elevated BP are consistent with some other publications related to vascular changes in hypertensive adolescents. Urbina et al reported higher pulse wave velocity and lower brachial artery dilation in hypertensive adolescents compared with normotensives, indicating relative vascular stiffness. Cerebrovascular abnormalities and alterations in cognitive function have also been demonstrated in untreated hypertensive adolescents compared with normotensives. Thus, evidence of target organ damage associated with hypertension in youth is not limited to the heart but extends to the vasculature. The issue of obesity is not directly addressed in the report by Park et al. Although, in Table 3 of their study, body mass index is a significant determinant of left ventricular mass index; and in the Table S2 in the online-only Data Supplement, body mass index is highest in quintile 5 (highest MAP quintile) with a mean of 23.6±7.0, indicating some participants in that quintile would be overweight or obese. It has been reported that among adolescents, adiposity, estimated by body mass index, has an effect on left ventricular mass index that is independent of BP. With regard to adiposity, it is of interest that a study, reported by Charakida et al on childhood obesity and vascular phenotypes was conducted on the same ALSPAC cohort when the participants were 10 to 11 years of age. In that study, adiposity measures, heart rate, BP, flow-mediated dilation in the brachial artery, and carotid-femoral pulse wave velocity were measured in 6576 children. Compared with normal weight children, overweight, and obese children, which comprised 20% of the entire cohort, had significantly higher BP, higher heart rate, larger brachial artery diameter, higher flow-mediated dilation, and lower pulse wave velocity. Cardiac output and TPR were not measured at age 10 to 11 years. However, higher flow-mediated dilation and lower pulse wave velocity in overweight/obese children with higher BP would indicate The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Division of Nephrology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA. Correspondence to Bonita Falkner, Division of Nephrology, Department of Medicine, Thomas Jefferson University, 833 Chestnut St, Suite 700, Philadelphia, PA 19107. Email [email protected] Cardiac Output Versus Total Peripheral Resistance A Wrinkle in Time