Screening and Management of Pediatric High Blood Pressure-Challenges to Implementing the Clinical Practice Guideline.

PURPOSE OF REVIEW: Elevated blood pressure (BP) and hypertension in childhood convey risk for hypertension and cardiovascular events in adulthood. Early recognition of abnormal BPs is key to preventing or lessening this risk. However, the process for making the diagnosis of hypertension is complex, and overall adherence to the 2017 American Academy of Pediatrics Clinical Practice Guidelines (CPG) is poor. We will review obstacles to adherence to the CPG and approaches designed to improve the diagnosis and management of hypertension in children. RECENT FINDINGS: Baseline data from the multi-center quality improvement intervention, "Boosting Primary Care Awareness and Treatment of Hypertension" (BP-CATCH), demonstrate that childhood hypertension remains underdiagnosed. Other studies confirm a lack of compliance with the process outlined in the CPG. The provision of electronic prompts, coaching, and education results in modest improvements. The combination of embedded medical record tools and education seems to offer the most hope for improvement.

Salt sensitivity of blood pressure in childhood and adolescence.

Although moderation of sodium intake is recommended population-wide, it remains uncertain who benefits from salt restriction. Salt sensitivity refers to changes in blood pressure in response to sodium intake and may occur with or without hypertension. Unfortunately, there is no practical way to assess salt sensitivity in daily practice. Assessment of salt sensitivity even in research studies is challenging with varying protocols utilized which may contribute to differing results. Building on studies in animals and adults, risk factors and conditions associated with salt sensitivity have been identified in the pediatric and young adult populations. This review presents the limited evidence linking obesity, low birth weight, diabetes, chronic kidney disease, and race/ethnicity with salt sensitivity in children, adolescents, and young adults. The impact of stress on sodium handling is also reviewed. The influence of age on the timing of introduction of dietary salt restriction and the long-term influence of salt sensitivity on risk for hypertension are considered. Lastly, interventions other than salt restriction that may improve salt sensitivity and may inform recommendations to families are reviewed.

Use of Automated Office Blood Pressure Measurement in the Evaluation of Elevated Blood Pressures in Children and Adolescents.

OBJECTIVES: To determine the level of agreement between automated office blood pressures (AOBP), auscultated or manual office BP (manual office blood pressure), and 24-hour ABPM, and to explore the ability of AOBP and manual office blood pressure to correctly identify daytime ambulatory hypertension in children. STUDY DESIGN: We retrospectively compared BPs obtained by AOBP and manual office blood pressure to predict daytime hypertension on ABPM. Six BPs were taken by AOBP followed by manual office blood pressure. Office hypertension was defined by BPs ≥95th percentile for sex and height percentiles for those <13 years of age and a BP of ≥130/80 mm Hg for ages ≥13 years. Daytime ambulatory hypertension was diagnosed if mean wake BPs were ≥95th percentile and BP loads were ≥25%. Application of adult ABPM thresholds for daytime hypertension (130/80 mm Hg) was assessed in ages ≥13 years. Sensitivity and specificity were calculated considering ABPM as the reference. RESULTS: Complete data were available for 187 patient encounters. Overall, the best agreement was found if both AOBP and manual office blood pressure showed hypertension, but owing to low sensitivity up to 49% of children with hypertension would be misclassified. The use of adult thresholds for ABPM did not improve agreement. CONCLUSIONS: Neither AOBP nor manual office blood pressure confirm or exclude daytime ambulatory hypertension with confidence. These results suggest an ongoing role for ABPM in evaluation of hypertension in children.

Changes in Ambulatory Blood Pressure Phenotype over Time in Children and Adolescents with Elevated Blood Pressures.

OBJECTIVE: To determine the stability of ambulatory blood pressure monitoring (ABPM) over time in children referred for evaluation of elevated BPs and assess for factors predicting change. STUDY DESIGN: This retrospective chart review conducted at Seattle Children's Hospital and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh identified 124 children referred for elevated BPs with 2 ABPM studies at least 6 months apart. All subjects received lifestyle counseling. Subjects with secondary hypertension (HTN) or on antihypertensive medication were excluded. ABPM phenotype was classified using American Heart Association guidelines as showing normal BP, prehypertension, and HTN. Generalized linear mixed effect regression models were used to regress stable, improving, or worsening HTN outcomes at study follow-up on baseline BP index and load variables. RESULTS: The median age of patients was 14.1 years (73% males) and the median interval between studies was 18 months. ABPM phenotype changed in 58 of 124 children, with 16% worsening and 31% improving. Older age was associated with persistence of HTN. Although not significant, decrease in body mass index z-score tracked with sustained normal ambulatory BPs. CONCLUSIONS: Although the sample size is small, our study suggests ABPM phenotype shows variability over time. Further study is required to identify factors supporting risk for progression of ABPM phenotype over time.

Angiotensin II and the Natriuretic and Blood Pressure Response to Mental Stress in African Americans.

Objective: To test the hypothesis that Angiotensin II (Ang II) is a contributing factor to the response pattern in African Americans (AAs) who retain rather than excrete sodium during mental stress. Design/Study Participants: Double-blind, randomized, cross-over trial of 87 healthy AAs aged 18 to 50 years. Interventions: The study participants received either a placebo or irbesartan, (150 mg PO), an Ang II receptor antagonist, for seven days prior to stress testing. Urinary sodium excretion (UNaV) and systolic blood pressure (SBP) were collected prior to and throughout a mental stress protocol (rest and stress period). Setting: A southeastern university. Main Outcome Measures: Ang II, SBP, and sodium retention. Results: During the placebo condition, 62 participants showed the expected increase in UNaV (excreters) while 25 participants reduced UNaV during stress (retainers). Irbesartan retainers demonstrated a reversal in the direction of their natriuretic response, now increasing UNaV in response to stress (∆ UNaV of -.094 mmol/min with placebo vs .052 mmol/min on irbesartan; P<.001). In excreters, irbesartan reduced SBP levels during both rest (-2.36 mm Hg; P=.03) and stress (-4.59;P<.0001), and an even more pronounced reduction in SBP was demonstrated by retainers on treatment during both rest (-4.29 mm Hg; P=.03) and stress (-6.12; P<.001). Conclusions: Ang II contributes to sodium retention in retainers. Furthermore, our findings indicate that suppression of Ang II has a beneficial effect on SBP during rest and stress in this population.

Stress and salt sensitivity in primary hypertension.

As the development of hypertension and target organ damage becomes more prevalent, it becomes exceedingly important to determine the underlying mechanisms through which this detrimental development occurs. Specifically, our studies and others have explored mechanisms through which stress elicits a salt-sensitive response in approximately 20-30 % of the population, resulting in the early development of hypertension and target organ damage. Data associated with this stress-induced cardiovascular response pattern have recently demonstrated additional effects across the body systems including factors contributing to the development of osteoporosis, obesity, autoimmune disease, and chronic inflammation. As each of these diseases become more prevalent in conjunction with hypertension, further research may discover stress and salt sensitivity to be at the "heart" of the matter for the development of many of today's most deadly conditions.

Ambulatory Blood Pressure and Number of Subclinical Target Organ Injury Markers in Youth: The SHIP AHOY Study.

Background: Hypertension in adolescence is associated with subclinical target organ injury (TOI). We aimed to determine whether different blood pressure (BP) thresholds were associated with increasing number of TOI markers in healthy adolescents. Methods: 244 participants (mean age 15.5±1.8 years, 60.1% male) were studied. Participants were divided based on both systolic clinic and ambulatory BP (ABP), into low- (<75 th percentile), mid- (75 th -90 th percentile) and high-risk (>90 th percentile) groups. TOI assessments included left ventricular mass, systolic and diastolic function, and vascular stiffness. The number of TOI markers for each participant was calculated. A multivariable general linear model was constructed to evaluate the association of different participant characteristics with higher numbers of TOI markers. Results: 47.5% of participants had at least one TOI marker: 31.2% had one, 11.9% two, 3.7% three, and 0.8% four. The number of TOI markers increased according to the BP risk groups: the percentage of participants with more than one TOI in the low-, mid-, and high groups based on clinic BP was 6.7%, 19.1%, and 21.8% (p=0.02), and based on ABP was 9.6%, 15.8%, and 32.2% (p<0.001). In a multivariable regression analysis, both clinic BP percentile and ambulatory SBP index were independently associated with the number of TOI markers. When both clinic and ABP were included in the model, only the ambulatory SBP index was significantly associated with the number of markers. Conclusion: High SBP, especially when assessed by ABPM, was associated with an increasing number of subclinical cardiovascular injury markers in adolescents.

Sodium intake and blood pressure in children.

Elevation of blood pressure (BP) and the risk for progression to hypertension (HTN) is of increasing concern in children and adolescents. Indeed, it is increasingly recognized that target organ injury may begin with even low levels of BP elevation. Sodium intake has long been recognized as a modifiable risk factor for HTN. While it seems clear that sodium impacts BP in children, its effects may be enhanced by other factors including obesity and increasing age. Evidence from animal and human studies indicates that sodium may have adverse consequences on the cardiovascular system independent of HTN. Thus, moderation of sodium intake over a lifetime may reduce risk for cardiovascular morbidity in adulthood. An appetite for salt is acquired, and intake beyond our need is almost universal. Considering that eating habits in childhood have been shown to track into adulthood, modest sodium intake should be advocated as part of a healthy lifestyle.

Association of Blood Pressure-Related Increase in Vascular Stiffness on Other Measures of Target Organ Damage in Youth.

BACKGROUND: Hypertension-related increased arterial stiffness predicts development of target organ damage (TOD) and cardiovascular disease. We hypothesized that blood pressure (BP)-related increased arterial stiffness is present in youth with elevated BP and is associated with TOD. METHODS: Participants were stratified by systolic BP into low- (systolic BP <75th percentile, n=155), mid- (systolic BP ≥80th and <90th percentile, n=88), and high-risk BP categories (≥90th percentile, n=139), based on age-, sex- and height-specific pediatric BP cut points. Clinic BP, 24-hour ambulatory BP monitoring, anthropometrics, and laboratory data were obtained. Arterial stiffness measures included carotid-femoral pulse wave velocity and aortic stiffness. Left ventricular mass index, left ventricular systolic and diastolic function, and urine albumin/creatinine were collected. ANOVA with Bonferroni correction was used to evaluate differences in cardiovascular risk factors, pulse wave velocity, and cardiac function across groups. General linear models were used to examine factors associated with arterial stiffness and to determine whether arterial stiffness is associated with TOD after accounting for BP. RESULTS: Pulse wave velocity increased across groups. Aortic distensibility, distensibility coefficient, and compliance were greater in low than in the mid or high group. Significant determinants of arterial stiffness were sex, age, adiposity, BP, and LDL (low-density lipoprotein) cholesterol. Pulse wave velocity and aortic compliance were significantly associated with TOD (systolic and diastolic cardiac function and urine albumin/creatinine ratio) after controlling for BP. CONCLUSIONS: Higher arterial stiffness is associated with elevated BP and TOD in youth emphasizing the need for primary prevention of cardiovascular disease.

Pediatric and Adult Ambulatory Blood Pressure Thresholds and Blood Pressure Load as Predictors of Left Ventricular Hypertrophy in Adolescents.

[Figure: see text].

Recurrent Page kidney in a child with a congenital solitary kidney requiring capsular artery embolization.

We report an unusual case of a child with a congenital solitary functional kidney complicated by a sports-related posttraumatic Page kidney. The child developed severe hypertension and renal insufficiency requiring percutaneous intervention to preserve renal function. The literature is sparse with no definitive guidelines for the treatment of Page kidney. Following the initial unsuccessful treatment with percutaneous drainage and sclerotherapy procedures, the child ultimately required catheter-directed particle embolization of the capsular arteries to resolve a recurrent subscapsular hematoma definitively. This was successful in preserving renal function and stabilization of the clinical manifestations of the Page kidney.

Subclinical Systolic and Diastolic Dysfunction Is Evident in Youth With Elevated Blood Pressure.

Hypertension is associated with cardiovascular events in adults. Subclinical changes to left ventricular strain and diastolic function have been found before development of decreased left ventricular ejection fraction and cardiovascular events. Our objective was to study effects of blood pressure (BP) on ventricular function in youth across the BP spectrum. Vital signs and labs were obtained in 346 participants aged 11 to 19 years who had BP categorized as low-risk (N=144; systolic BP <75th percentile), mid-risk (N=83; systolic BP ≥80th and <90th percentile), and high-risk (N=119; systolic BP ≥90th percentile). Echocardiography was performed to assess left ventricular strain and diastolic function. Differences between groups were analyzed by ANOVA. General linear models were constructed to determine independent predictors of systolic and diastolic function. Mid-risk and high-risk participants had greater adiposity and more adverse metabolic labs (lower HDL [high-density lipoprotein], higher glucose, and higher insulin) than the low-risk group. Mid-risk and high-risk participants had significantly lower left ventricular ejection fraction and peak global longitudinal strain than the low-risk group (both P≤0.05). The E/e' ratio was higher in the high-risk group versus the low-risk and mid-risk groups, and the e'/a' ratio was lower in the high-risk versus the low-risk group (both P≤0.05). BP and adiposity were statistically significant determinants of left ventricular systolic and diastolic function. Subclinical changes in left ventricular systolic and diastolic function can be detected even at BP levels below the hypertensive range as currently defined.

Stress-induced sodium retention and hypertension: a review and hypothesis.

Hypertension--an important health problem in industrialized nations--is particularly significant in blacks and obese individuals, in whom it is hypothesized to result from impaired renal sodium regulation. We reviewed studies that identified individuals with impaired sodium regulation by examining the natriuretic response to mental stress. A significant percentage of black and obese individuals retain or have a diminished natriuretic response to mental stress despite increased blood pressure (BP). This contributes a volume component to the normal resistance-mediated BP increase, and BP remains elevated after the stressor ceases until the volume expansion diminishes. The stress exposes these individuals to greater cardiovascular load. This response pattern has been linked to renin-angiotensin-aldosterone system activity, and is associated with premature target-organ damage. Assessing stress-induced sodium retention provides a method to identify patients with impaired sodium regulation without using a dietary protocol that poses adherence difficulties, or complicated laboratory assessments. Furthermore, research using this technique indicates the effectiveness of renin-angiotensin-aldosterone system blockers in correcting impaired sodium regulation and consequent hypertension in these individuals.

Prediction of Ambulatory Hypertension Based on Clinic Blood Pressure Percentile in Adolescents.

Ambulatory blood pressure (BP) monitoring provides a more precise measure of BP status than clinic BP and is currently recommended in the evaluation of high BP in children and adolescents. However, ambulatory BP monitoring may not always be available. Our aim was to determine the clinic BP percentile most likely to predict ambulatory hypertension. We evaluated clinic and ambulatory BP in 247 adolescents (median age, 15.7 years; 63% white; 54% male). Clinic BP percentile (based on the fourth report and the 2017 American Academy of Pediatrics clinical practice guidelines) and ambulatory BP status (normal versus hypertension) were determined by age-, sex-, and height-specific cut points. Sensitivity and specificity of different clinic BP percentiles and cutoffs to predict ambulatory hypertension were calculated. Forty (16%) and 67 (27%) patients had systolic hypertension based on the fourth report and the 2017 guidelines, respectively, whereas 38 (15%) had wake ambulatory systolic hypertension. The prevalence of ambulatory wake systolic hypertension increased across clinic systolic BP percentiles, from 3% when clinic systolic BP was <50th percentile to 41% when ≥95th percentile. The 2017 guidelines' 85th systolic percentile had similar sensitivity (86.8%) and better specificity (57.4% versus 48.1%) than elevated BP (≥90th percentile or ≥120 mm Hg) to diagnose ambulatory hypertension. When evaluating adolescents for hypertension, 2017 guidelines' clinic systolic 85th percentile may be the optimal threshold at which to perform ambulatory BP monitoring.

SHIP-AHOY (Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth).

Although hypertension is identifiable in children and adolescents, there are many knowledge gaps on how to best define and manage high blood pressure in the young. SHIP-AHOY (Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth) is being conducted to address these knowledge gaps. Five hundred adolescents will be recruited and will undergo ambulatory blood pressure monitoring, echocardiographic, vascular, and cognitive assessments, as well as epigenetic studies to identify mechanisms that underlie the development of hypertensive target organ damage. Details of the design and methods that will be utilized in SHIP-AHOY are presented here, as well as baseline characteristics of the first 264 study participants. The primary aim of the study is to develop a risk-based definition of hypertension in the young that will result in better understanding of the transition from blood pressure in youth to adult cardiovascular disease.

Ethnic and gender differences in ambulatory blood pressure trajectories: results from a 15-year longitudinal study in youth and young adults.

BACKGROUND: Cross-sectional studies demonstrated ethnic and gender differences in ambulatory blood pressure patterns, but little is known about the longitudinal development of these differences. METHODS AND RESULTS: Twenty-four-hour ambulatory blood pressure was measured up to 12 times (5 times on average) over a 15-year period in 312 African Americans (AAs) and 351 European Americans aged 7 to 30 years. Multivariate individual growth curves across age were created for daytime and nighttime blood pressure jointly. For both daytime and nighttime systolic blood pressure (SBP), AAs and males had higher levels (P<0.001) than European Americans and females. Males also showed a greater increase with age (P<0.001) than females. For nighttime SBP, a faster increase of SBP with age (P<0.01) in AAs was additionally observed. The ethnic difference in nighttime SBP levels and its increase with age were significantly larger than in daytime SBP. For daytime and nighttime diastolic blood pressure, AAs had higher levels than European Americans (P<0.001), and this difference was significantly larger at night. From late adolescence onward, males showed a greater increase in diastolic blood pressure with age than females. Ethnic and gender differences persisted after adjustment for height, body mass index, socioeconomic status, and stress-related coping styles. Family history of essential hypertension explained ethnic differences in daytime SBP. CONCLUSIONS: We observed significant ethnic and gender differences in longitudinal trajectories of ambulatory blood pressure in youth and young adults. The blunted nocturnal decline and its exacerbation with age in AAs corroborate and extend findings of cross-sectional studies.

Diagnosis and management of white-coat hypertension in children and adolescents: A Midwest Pediatric Nephrology Consortium study.

Although the definition of white-coat hypertension (WCH) in children and adolescents is clearly defined, little is known about how this condition is actually approached clinically. To better understand the contemporary approach to the diagnosis and management of WCH in pediatric patients, the authors surveyed the membership of the Midwest Pediatric Nephrology Consortium. Seventy-four faculty pediatric nephrologists responded to the survey. The survey results demonstrated uniformity in diagnosing WCH, including ambulatory blood pressure monitoring use in 93% of the respondents and a 75% adherence rate according to the 2014 American Heart Association scientific statement on pediatric ambulatory blood pressure monitoring. A total of 85% of respondents would not embark on further diagnostic evaluation once the WCH diagnosis was established, and none would initiate antihypertensive medications. There was a wide variety of practice habits in follow-up of WCH including frequency of office and out-of-office follow-up blood pressure measurements, the setting and timing of physician follow-up, and the role of repeat ambulatory blood pressure monitoring. The results of this survey highlight the need for prospective studies aimed at establishing the optimal approach to pediatric patients with WCH.

Ambulatory Blood Pressure Control in Children and Young Adults After Kidney Transplantation.

BACKGROUND: Ambulatory blood pressure (BP) monitoring (ABPM) is the preferred method to characterize BP status, and its use in kidney transplant recipients is increasing. Data on longitudinal ambulatory BP (ABP) trends in pediatric and young adult kidney transplant recipients are limited. METHODS: Retrospective review of a large cohort of children and young adults following kidney transplantation and evaluation of their ABP status over time and its associations with any patient and clinical characteristics. RESULTS: Two hundred and two patients had baseline ABPM available for analysis, and 123 of them had a follow up (median time 2.3 years) ABPM. At the time of follow up, more patients were treated for hypertension (80% vs. 72%, P = 0.02), and less patients had ambulatory hypertension (36% vs. 54%, P = 0.005), uncontrolled or untreated, compared with baseline, with 45% of all patients classified as having controlled hypertension (compared to 26% at baseline, P = 0.002). Prevalence of ambulatory hypertension decreased only in patients who were less than 18 years old at baseline. High baseline mean 24-hour systolic BP was independently associated with persistent hypertension. CONCLUSIONS: In young kidney transplant recipients followed by ABPM, the prevalence of ambulatory hypertension decreases over time, mainly due to the increased number of patients with controlled hypertension.