Ronald J. Portman

Ambulatory Blood Pressure and Left Ventricular Mass Index in Hypertensive Children

To determine whether ambulatory blood pressure is more predictive of left ventricular hypertrophy than is casual blood pressure in hypertensive children, echocardiography and ambulatory blood pressure data from 37 untreated hypertensive children were analyzed. Left ventricular mass was calculated using the Devereux equation, left ventricular mass index was calculated as left ventricular mass (in grams)/height2.7 (in meters), and left ventricular hypertrophy was defined as left ventricular mass index >51 g/m2.7. Average blood pressure, blood pressure load, and blood pressure index (average blood pressure divided by pediatric ambulatory blood pressure 95th percentile) were calculated. Left ventricular mass index was strongly correlated with 24-hour systolic blood pressure index (r =0.43, P =0.008) and was also correlated with 24-hour systolic blood pressure (r =0.34, P =0.037), 24-hour systolic blood pressure load (r =0.38, P =0.020), wake systolic blood pressure load (r =0.37, P =0.025), sleep systolic blood pressure (r =0.33, P =0.048), and sleep systolic blood pressure load (r =0.38, P =0.021). Left ventricular mass index did not correlate with age, weight, clinic blood pressure, or ambulatory diastolic blood pressure. The overall prevalence of left ventricular hypertrophy was 27%. The prevalence of left ventricular hypertrophy was 47% (8 of 17) in patients with both systolic blood pressure load >50% and 24-hour systolic blood pressure index >1.0, compared with 10% (2 of 20) in patients without both criteria (P =0.015). These data suggest ambulatory blood pressure monitoring may be useful for the clinical assessment of hypertensive children by identifying those at high risk for the presence of end organ injury.

Determination of Blood Pressure Percentiles in Normal-Weight Children: Some Methodological Issues

Blood pressure in children has consistently been related to adult blood pressure, with implications for long-term prevention of cardiovascular disease. The epidemic of obesity in children has resulted in corresponding increases in childhood blood pressure. In this paper, the authors develop norms for childhood blood pressure among normal-weight children (body mass index <85th percentile based on Centers for Disease Control and Prevention guidelines) as a function of age, sex, and height, using data from 49,967 children included in the database of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (the Pediatric Task Force). The authors considered three types of models for pediatric blood pressure data, including polynomial regression, restricted cubic splines, and quantile regression, with the latter providing the best fit. The sex-specific norms presented here are a nonlinear function of both age and height and are generally slightly lower than previously developed norms based on Pediatric Task Force data including both normal-weight and overweight children.

Left Ventricular Hypertrophy in Hypertensive Adolescents Analysis of Risk by 2004 National High Blood Pressure Education Program Working Group Staging Criteria

The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recently recommended staging hypertension (HTN) in children and adolescents based on blood pressure severity. The use of blood pressure staging and its corresponding therapeutic approach was examined in this pooled analysis assessing the risk for end-organ damage, specifically left ventricular hypertrophy among hypertensive adolescents stratified by working group criteria. Newly diagnosed hypertensive adolescents and normotensive control subjects similar in age, race/ethnicity, gender, and body mass index completed casual and 24-hour ambulatory blood pressure measurements, M-mode echocardiography, and fasting serum laboratories. Hypertensive subjects had higher insulin and cholesterol but similar glucose levels as compared with control subjects. Among subjects with stage 1 HTN by casual blood pressure, 34% had white-coat HTN as opposed to 15% of stage 2 hypertensive subjects. Of the subjects with normal casual measurements, 20% had HTN by ambulatory monitoring. Subjects with stage 2 HTN by casual measurement alone (odds ratio: 4.13; 95% CI: 1.04 to 16.48) and after 24-hour ambulatory confirmation (odds ratio: 7.23; 95% CI: 1.28 to 40.68) had increased odds for left ventricular hypertrophy. In addition, the risk for left ventricular hypertrophy was similar for subjects with masked and confirmed stage 1 HTN, whereas subjects with white-coat HTN had a risk comparable to normotensive subjects. Thus, recommendations that adolescents with stage 2 HTN by casual measurements alone receive medication initially along with therapeutic lifestyle counseling are reasonable, though ambulatory blood pressure monitoring remains a valuable tool for evaluating children with stage 2 HTN, because >10% have white-coat HTN.

Evaluation of white coat hypertension in children : Importance of the definitions of normal ambulatory Blood Pressure and the severity of casual hypertension

To better describe the phenomenon of white coat hypertension (WCH) in children, we reviewed our single-center experience using ambulatory blood pressure monitoring to determine: 1) how the choice of threshold limits for defining ambulatory hypertension affects the determination of WCH, and 2) whether the severity of casual hypertension predicts the occurrence of WCH. Using the same daytime ambulatory blood pressure (ABP) data from 71 children (age 11.9 3.4 years) with persistently elevated casual blood pressure (BP), the prevalence of WCH was compared using 95th percentile BP limits from the Task Force on High Blood Pressure in Children (TF) and from normative pediatric daytime ambulatory BP (ABP) data. To quantify casual hypertension severity, average clinic BP was divided by the patient-specific TF 95th percentile BP to generate a BP index (ie, BP index of 1.1=10% above 95th percentile). The WCH prevalence was lower by normative ABP criteria than by TF criteria (31% v 59%, P < .001), but did not vary significantly by age, gender, race, or body mass index. Logistic regression showed that higher systolic BP index (P < .001) or diastolic BP index (P < .01) was associated with a lower probability of WCH. Specifically, as systolic BP index increased from 1.0 to 1.2, the estimated probability of WCH decreased from 87% to 15%, respectively. These data suggest that the use of the lower TF limits, derived solely from resting BP measurements, may overestimate WCH prevalence in ambulatory children. In addition, these data confirm in children the finding in adults that WCH is highly prevalent when casual hypertension is borderline or mild, but uncommon when moderate or severe.

Blood pressure variability and classification of prehypertension and hypertension in adolescence.

OBJECTIVE. There is little information in pediatrics on the persistence of the prehypertension and hypertension classifications or on the progression of prehypertension to hypertension. This study aimed to examine those issues. METHODS. An analysis of data from the National Childhood Blood Pressure database was conducted to examine the longitudinal blood pressure outcomes for adolescents classified after a single measurement of blood pressure. Adolescent subjects (N = 8535) for whom serial single blood pressure measurements were obtained at intervals of 2 years were identified. Subjects were stratified according to blood pressure status at the initial measurement, as having normotension, prehypertension, or hypertension. RESULTS. Among subjects designated as having prehypertension (n = 1470), 14% of boys and 12% of girls had hypertension 2 years later. Among subjects designated as having hypertension, 31% of boys and 26% of girls continued to exhibit hypertension, and 47% of boys and 26% of girls had blood pressure values in the prehypertensive range. Regression models showed no significant effect of race on blood pressure changes but significant effects of initial BMI and changes in BMI. CONCLUSIONS. These data indicated that the rate of progression of prehypertension to hypertension was ∼7% per year. Prehypertension can be predictive of future hypertension and may benefit from preventive interventions, especially lifestyle changes.

Abnormal 24-hour blood pressure patterns in children after renal transplantation.

Hypertension after renal transplantation occurs commonly and is associated with decreased allograft survival. Hypertension is usually diagnosed by casual blood pressure (BP) measurements in the outpatient clinic that may not reflect the overall 24-hour BP pattern. To better describe the pattern of BP in children after renal transplantation, 24-hour ambulatory BP monitoring (APBM) was performed in 42 patients with stable renal function. BP was measured every 20 minutes during the daytime and every 30 minutes at night. Mean patient age was 12.8 +/- 5.2 years, and mean time after transplantation was 34 +/- 36 months. Seventy-six percent of the patients were administered antihypertensive medications. Twenty-four-hour mean systolic BP (SBP) was 127 +/- 11 mm Hg, and diastolic BP (DBP) was 80 +/- 11 mm Hg. Mean 24-hour BP load values (percentage of BP readings > 95th percentile based on Task Force criteria) were 59% for SBP and 50% for DBP, which were significantly elevated compared with healthy children (P < 0.001). An attenuated decline in sleep BP (nondipping) was found in 78% of the patients for SBP and 50% for DBP. Sleep BP exceeded awake BP in 24% of the patients for SBP and 17% for DBP. Boys had a greater SBP load (66% versus 45%; P = 0.03) and DBP load (57% versus 38%; P = 0.04) than girls. These results confirm in children the high prevalence of hypertension by ABPM criteria after renal transplantation and show attenuation of normal sleep BP decreases. These BP disturbances may shorten renal allograft survival and predispose children to long-term hypertensive end-organ damage.

Cardiovascular Risk Factors and Sequelae in Hypertensive Children Identified by Referral Versus School-Based Screening

Abstract—To determine whether systematic differences exist between hypertensive children referred for evaluation by primary care providers and children identified through community-based screening, cardiovascular risk factors and surrogate markers of hypertensive injury were compared based on subject source (referral versus screening). Children referred to a hypertension clinic for persistently elevated blood pressure were compared with children identified as hypertensive during school screening of 5102 students in Houston public schools. M-mode echocardiography of the left ventricle was performed and subsequently reviewed by 2 independent sonographers blinded to identifying subject information. Subsets of subjects also underwent carotid artery ultrasound for measurement of intimal-medial thickness, overnight urine collections for microalbuminuria, and fasting serum cholesterol, triglycerides, and glucose. Ninety-seven total subjects (54 screening and 43 referral) met inclusion criteria and had technically adequate echocardiography performed. The prevalence of left ventricular hypertrophy (LVH) was 37%. Referral subjects demonstrated significantly greater left ventricular mass index (38.8 versus 34.2 g/m2.7; P <0.01) and a higher prevalence of LVH (49% versus 28%; P <0.05). Among subjects who underwent carotid ultrasound (n=75), carotid intimal-medial thickness was significantly higher in referral subjects (0.61 versus 0.57, P <0.05). When controlling for BMI z score, which was significantly higher in referral subjects, systematic differences by subject source did not persist. These findings suggest that hypertensive children who are predominantly overweight, independent of the manner in which patients come to medical attention, will manifest evidence of more severe cardiovascular disease assessed by surrogate markers such as left ventricular mass index or carotid artery intimal medial thickness.

Is the Extrapolated Adult Dose of Fosinopril Safe and Effective in Treating Hypertensive Children

We evaluated the efficacy, safety, and dose–response relationship of fosinopril in children aged 6 to 16 years with hypertension or high-normal blood pressure with an associated medical condition requiring treatment. The study was a prospective, double-blind, placebo-controlled trial conducted in 78 clinical sites in the United States, Russia, and Israel. There were 4 phases: a screening phase of 10 days maximum, a 4-week dose–response phase, a placebo withdrawal phase of 2 weeks maximum, and a 52-week open-label safety phase. The primary objective of the dose–response phase was to determine whether low (0.1 mg/kg), medium (0.3 mg/kg), or high (0.6 mg/kg) doses of fosinopril based on established adult dosing affect trough seated systolic blood pressure. During the dose–response phase, all 3 doses were equally effective in lowering systolic blood pressure. During the placebo withdrawal phase, there was an adjusted mean systolic blood pressure increase of 5.2 mm Hg for the placebo group and 1.5 mm Hg for the fosinopril group, a net withdrawal effect of 3.7 mm Hg (P=0.013). Fosinopril was well tolerated; serious adverse events occurred infrequently and were generally not attributed to fosinopril. Because children appear to be more sensitive to lower doses of fosinopril than adults, starting doses for children should be ≤0.1 mg/kg.

Efficacy, Safety, and Pharmacokinetics of Candesartan Cilexetil in Hypertensive Children Aged 6 to 17 Years

This 4‐week randomized, double blind, placebo‐controlled study (N=240), 1‐year open label trial (N=233), and single‐dose pharmacokinetic study (N=22) evaluated candesartan cilexetil (3 doses) in hypertensive children aged 6 to 17 years. Seventy‐one percent were 12 years of age or older, 71% were male, and 47% were black. Systolic (SBP)/diastolic (DBP) blood pressure declined 8.6/4.8–11.2/8.0 mm Hg with candesartan and 3.7/1.8 mm Hg with placebo (P<.01 compared to placebo for SBP and for the mid and high doses for DBP; placebo‐corrected 4.9/3.0–7.5/6.2 mm Hg). The slopes for dose were not, however, different from zero (P>.05). The response rate (SBP and DBP <95th percentile) after 1 year was 53%. The pharmacokinetic profiles in 6‐ to 12‐ and 12‐ to 17‐year‐olds were similar and were comparable to adults. Eight candesartan patients discontinued treatment because of an adverse event. Candesartan is an effective, well‐tolerated antihypertensive agent for children aged 6 to 17 years and has a pharmacokinetic profile that is similar to that in adults.

Ambulatory blood pressure monitoring in pediatric renal transplantation

Abstract: Over last two decades ABPM has evolved from a research device to an established and valuable clinical tool for BP evaluation. More than 10 yrs ago ABPM was introduced to pediatrics and since that time, its importance has been increasing in the management of hypertension in children and adolescents. This review summarizes the information gathered from the studies of ABPM in adult and pediatric patients with renal transplants. We will review the importance of hypertension in this patient subset, discuss the advantage of ABPM over CBP and focus on specific abnormalities and clinical significance of ABPM in renal transplant recipients.