Race and Obesity in Adolescent Hypertension.

BACKGROUND AND OBJECTIVES: The overall prevalence of essential hypertension in adolescents may be growing. Differences in blood pressure (BP) are well established in adults, but are less clear in adolescents. We hypothesize that the prevalence of hypertension differs by race/ethnicity among adolescents at school-based screenings. METHODS: We performed school-based BP screening in over 20 000 adolescents from 2000 to 2015. Race/ethnicity was self-reported. Height and weight were measured to determine BMI, and BP status was confirmed on 3 occasions to diagnose sustained hypertension according to Fourth Working Group Report criteria. RESULTS: We successfully screened 21 062 adolescents aged 10 to 19 years (mean, 13.8 years). The final prevalence of sustained hypertension in all subjects was 2.7%. Obesity rates were highest among African American (3.1%) and Hispanic (2.7%) adolescents. The highest rate of hypertension was seen in Hispanic (3.1%), followed by African American (2.7%), white (2.6%), and Asian (1.7%) adolescents (P = .019). However, obese white adolescents had the highest prevalence of sustained hypertension (7.4%) compared with obese African American adolescents (4.5%, P < .001). At lower BMI percentiles (<60th percentile), Hispanic adolescents actually had the lowest predicted prevalence of hypertension among the 4 groups. CONCLUSIONS: The prevalence of hypertension varies among different race/ethnicities. Although obesity remains the strongest predictor of early hypertension, the strength of this relationship is intensified in Hispanic and white adolescents, whereas it is lessened in African American adolescents.

Left Ventricular Hypertrophy Phenotype in Childhood-Onset Essential Hypertension.

The aim of this study was to determine the risk factors associated with left ventricular (LV) hypertrophy (LVH) among 89 untreated children with primary hypertension. Clinic hypertension was confirmed by 24-hour ambulatory blood pressure (BP) monitoring. LV mass (LVM) index was calculated as LVM (g)/height (m)(2.7) and LVH was defined as LVM index >95th percentile. Children with (n=32) and without (n=57) LVH were compared. Both obesity and systolic BP were independently associated with LVH, with a higher contribution by body mass index. Obesity contributed significantly, with a nearly nine-fold increased risk of LVH. There was evidence of effect modification by the presence or absence of obesity on the relationship between systolic BP and LVH, whereby the relationship existed mainly in nonobese rather than obese children. Hence, to achieve reversal of LVH, clinicians should take into account both BP control and weight management.

Myocardial Performance Index in Childhood Onset Essential Hypertension and White Coat Hypertension.

BACKGROUND: As a global measure of ventricular systolic and diastolic function, the myocardial performance index (MPI) can be an early indicator of hypertensive cardiomyopathy in children with essential hypertension (EH). METHODS: Children with untreated newly diagnosed EH and white coat hypertension (WCH) by a 24-hour ambulatory blood pressure monitoring (ABPM), both groups without any identifiable etiology for the hypertension, were enrolled for the study. Echocardiograms and vascular ultrasounds for carotid artery intimal medial thickness were performed on all children prior to therapy. Diastolic function (peak E and A velocities, E/A ratio, isovolumic relaxation time, and deceleration times) and MPI were evaluated by simultaneous transmitral and transaortic spectral Doppler flow velocities. Systolic function was evaluated by shortening fraction and ejection fraction. RESULTS: A cohort of 66 children (24 with EH, 42 with WCH, males 61%, median age of 13 years, range 10-17 years) were enrolled in the study. The demographic, anthropometric, laboratory tests, vascular ultrasound, and conventional echocardiographic parameters were similar between the 2 groups. There was a very small difference in MPI between the EH and WCH children (0.28 SD: 0.07 vs. 0.31 SD: 0.08, P = 0.045). However, in EH children, MPI increased by 0.14 units for every 10 unit increase in mean ABPM systolic BP (95% confidence interval: 0.03-0.25). CONCLUSIONS: We found the increasing MPI was associated with increasing 24-hour mean systolic BP in children with EH. Therefore, MPI may have utility as a single, quick, noninvasive method of detection and tracking of subclinical hypertensive heart disease.

Accuracy of the Spacelabs 90217 ambulatory blood pressure monitor in a pediatric population.

BACKGROUND: Ambulatory blood pressure monitoring techniques provide unique advantages for diagnosing hypertension, although few devices have been independently validated in the pediatric population. METHODS: We sought to validate the accuracy of ambulatory blood pressure monitoring with the Spacelabs 90217 monitor in children using a modified British Hypertension Society protocol. RESULTS: A total of 112 children, aged between 6 and 17 years, completed the study at one of the three participating centers. Overall, the monitor earned an 'A' for systolic blood pressure and 'B' for diastolic blood pressure. It performed slightly better among 6-12 year olds (A/A) compared with 13-17 year olds (A/B). CONCLUSIONS: We conclude that the Spacelabs 90217 monitor is an appropriate monitor for use in children who are 6 years of age or older.

Detection of early diastolic alterations by tissue Doppler imaging in untreated childhood-onset essential hypertension.

The aim of the study was to determine the presence of preclinical diastolic dysfunction in hypertensive children relative to normotensive children by Tissue Doppler Imaging (TDI). We prospectively enrolled children with untreated essential hypertension in absence of any other disease and a matched healthy control group with normal blood pressure (BP); both groups confirmed by clinic BP and a 24-hour ambulatory BP monitoring. Echocardiographic diastolic parameters were determined using spectral transmitral inflow Doppler, flow propagation velocity, TDI, and systolic parameters were determined via midwall shortening fraction and ejection fraction. A total of 80 multiethnic children were prospectively enrolled for the study: 46 hypertensive (median age, 13 years; 72% males) and 34 control (median age, 14 years; 65% males). The only echocardiography parameters that had a statistically significant change compared with the control children, were regional mitral Ea, Aa, and the E/Ea ratio by TDI. In comparison with controls, hypertensive children had lower Ea and Aa velocities of anterior and posterior walls and higher lateral wall E/Ea ratio. The decrease in posterior wall Ea and Aa remained significant after adjustment for gender, age, body mass index, ethnicity, and left ventricular hypertrophy on multivariate analysis. The lateral and septal wall E/Ea ratios correlated significantly with fasting serum insulin levels on similar multivariate analysis. Decreased regional TDI velocities were seen with preserved left ventricular systolic function even when other measures of diastolic dysfunction remained unchanged in untreated hypertensive children. Hypertension and serum insulin levels had strong associations with preclinical diastolic alterations in children.

Screening blood pressure measurement in children: are we saving lives?

Blood Pressure screening in children and adolescents is currently recommended by several prominent medical organizations, including the American Heart Association, the National High Blood Pressure Education Program, the National Heart, Lung, and Blood Institute, the European Society of Hypertension, and the American Academy of Pediatrics. This practice was recently subject to intense scientific review by the U.S. Preventive Services Task Force. The conclusion of the Task Force was that "current evidence is insufficient to assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents." This commentary provides an alternate interpretation of current evidence for blood pressure screening in children and adolescents and highlights its importance as a part of routine medical care.

Progression of prehypertension to hypertension in adolescents.

In the 2004 report from the National High Blood Pressure (BP) Education Program Working Group on BP in Children and Adolescents, the term "high normal BP" was replaced with the designation "prehypertension". It was proposed that BP levels that were higher than normal but did not reach the level of hypertension posed an increased risk for progression to hypertension. The overall intent of this description was to help identify children who were at the greatest risk for the development of hypertension. These are children and adolescents for whom targeted prevention programs are expected to be most beneficial. Following the 2004 report, the prehypertension condition has been examined and described in adolescents as well as adults. This review summarizes the knowledge that has been gained on prehypertension including clinical characteristics, rates of progression to hypertension, and evidence of cardiovascular pathology.

Prehypertension in adolescents: risk and progression.

In 2004, the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recommended a new designation of prehypertension for children with mildly elevated blood pressure (BP). This description was intended to help identify children most at risk for the development of persistent hypertension for whom targeted prevention programs would be most beneficial and was based largely on expert opinions and epidemiologic normal values. This review summarizes the knowledge that has been gained regarding the epidemiology and risk associated with prehypertension in adolescents since its inception and highlights future challenges in understanding and preventing the development of hypertensive disease in this population.

Effect of placebo on ambulatory blood pressure monitoring in children.

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) has been proposed as a useful tool for more accurately diagnosing hypertension (HTN) and evaluating blood pressure (BP) response in pediatric anti-hypertensive trials. ABPM captures multiple BP measurements during routine daily activities and is thus an excellent method for identifying white-coat HTN. Additionally, ABPM measurements in adults do not demonstrate the placebo effect commonly seen with casual BP measurements, although this has yet to be evaluated in children. Therefore,, the aim of this study was to assess the effect of placebo on ABPM measurements in children. METHODS: A total of 141 children aged 5-16 years with elevated BP were randomized into a multi-center, single-blind, cross-over trial. Subjects received a placebo pill prior to wearing a 24-h ABPM device at one of two visits separated by 1-2 weeks. Study procedures were otherwise identical at both visits. RESULTS: Mean systolic and diastolic BP for all measured time periods were similar between visits, as was the number of children diagnosed with HTN at each visit. CONCLUSION: Having confirmed HTN at baseline did not affect the impact of placebo on mean BP. If confirmed, this lack of placebo effect on ABPM measurements may allow for the design of direct comparison pediatric anti-hypertensive trials without a placebo arm.

Development of hypertension in adolescents with pre-hypertension.

OBJECTIVE: To evaluate the risk for developing incident hypertension (HTN) in adolescents with pre-hypertension. STUDY DESIGN: A secondary analysis of students participating in multiple school-based blood pressure (BP) screens from 2000 to 2007 was completed. At each screen, height, weight, and 2 to 4 BPs were measured on as many as 3 occasions when BP remained ≥ 95th percentile. Students with confirmed HTN at their initial screen were excluded, and incident HTN was defined as having a BP ≥ 95th percentile at all 3 visits of a later screen. Incidence rates (IR) and hazard ratios (HR) were calculated by using Cox Proportional models. RESULTS: Of 1006 students, HTN developed in 11 (IR 0.5%/year) in a mean of 2.1 years of observation. IRs were higher in "at-risk" students (pre-hypertensive or hypertensive with follow-up BP <95th percentile), 1.4%/year (HR, 4.89; 1.48-16.19) and students with a BP ≥ 90th percentile at 3 baseline visits, 6.6%/year HR 24.33 (5.68-104.29)]. Although not significant, students with pre-hypertension by the 2004 Task Force definition also had an increased IR of 1.1%/year (HR, 2.98; 0.77-11.56)]. CONCLUSION: Elevated BP increases the risk for the development of HTN during adolescence. Effective strategies for preventing HTN in at-risk adolescents are needed.

Prevalence of persistent prehypertension in adolescents.

OBJECTIVE: To measure the prevalence of persistent prehypertension in adolescents. STUDY DESIGN: We collected demographic and anthropometric data and 4 oscillometric blood pressure (BP) measurements on 1020 students. The mean of the second, third, and fourth BP measurements determined each student's BP status per visit, with up to 3 total visits. Final BP status was classified as normal (BP <90th percentile and 120/80 mm Hg at the first visit), variable (BP ≥ 90th percentile or 120/80 mm Hg at the first visit and subsequently normal), abnormal (BP ≥ 90th percentile or 120/80 mm Hg at 3 visits but not hypertensive), or hypertensive (BP ≥ 95th percentile at 3 visits). The abnormal group included those with persistent prehypertension (BP ≥ 90th percentile or 120/80 mm Hg and <95th percentile on 3 visits). Statistical analysis allowed for comparison of groups and identification of characteristics associated with final BP classification. RESULTS: Of 1010 students analyzed, 71.1% were classified as normal, 15.0% as variable, 11.5% as abnormal, and 2.5% as hypertensive. The prevalence of persistent prehypertension was 4.0%. Obesity similarly affected the odds for variable BP (OR, 3.9; 95% CI, 2.5-6.0) and abnormal BP (OR, 3.4; 95% CI, 2.0-5.9), and dramatically increased the odds for hypertension (OR, 38.4; 95% CI, 9.4-156.6). CONCLUSION: Almost 30% of the students had at least one elevated BP measurement significantly influenced by obesity. Treating obesity may be essential to preventing prehypertension and/or hypertension.

Testosterone administration decreases generosity in the ultimatum game.

How do human beings decide when to be selfish or selfless? In this study, we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design. We also confirmed participants' testosterone levels before and after treatment through blood draws. Using the Ultimatum Game from behavioral economics, we find that men with artificially raised T, compared to themselves on placebo, were 27% less generous towards strangers with money they controlled (95% CI placebo: (1.70, 2.72); 95% CI T: (.98, 2.30)). This effect scales with a man's level of total-, free-, and dihydro-testosterone (DHT). Men in the lowest decile of DHT were 560% more generous than men in the highest decile of DHT. We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them. Our results continue to hold after controlling for altruism. We conclude that elevated testosterone causes men to behave antisocially.

Effects of NMDA receptor antagonists on acute mu-opioid analgesia in the rat.

Mixed research findings have led to a debate regarding the effect of N-methyl-D-aspartate (NMDA) receptor antagonists on opiate analgesia. NMDA antagonists have been found in various studies to enhance, to inhibit, or to have no effect on opiate analgesia. The present research used a single protocol to explore the effects of six NMDA receptor antagonists on acute morphine (3.0 mg/kg s.c.) and fentanyl (0.05 mg/kg s.c.) analgesia in adult male Sprague-Dawley rats. NMDA receptor antagonists were selected based on their abilities to block various sites on the NMDA receptor complex, including the noncompetitive antagonists MK-801 (0.1 and 0.3 mg/kg i.p.), dextromethorphan (10.0 and 30.0 mg/kg i.p.), and memantine (3.0 and 10.0 mg/kg i.p.), a glycine site antagonist, (+)-HA-966 (10.0 and 30.0 mg/kg i.p.), a competitive antagonist, LY235959 (1.0 and 3.0 mg/kg i.p.), and a polyamine site antagonist, ifenprodil (1.0 and 3.0 mg/kg i.p.). Analgesia was assessed using the tail-flick test. A single dose of each opiate was used. The low doses of the antagonists, which are known to produce significant neural and behavioral actions at NMDA receptors, had no effect on morphine or fentanyl analgesia. At the higher doses, morphine analgesia was significantly enhanced by LY235959 (3.0 mg/kg), and fentanyl analgesia was significantly enhanced by LY235959 (3.0 mg/kg), dextromethorphan (30.0 mg/kg), and (+)-HA-966 (30.0 mg/kg). Enhancement of analgesia occurred without any apparent adverse side effects. None of the NMDA antagonists affected tail-flick responses on their own, except the higher dose of LY235959 (3.0 mg/kg), which produced a mild analgesic effect. Because no consistent effects were observed, the data suggest that NMDA receptors are not involved in acute mu-opioid analgesia. The mechanisms underlying the enhancement of opiate analgesia by selected NMDA antagonists, such as LY235959, dextromethorphan, and (+)-HA-966, remain to be determined.