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.

Medication fill duration in pediatric hypertension: adherence, blood pressure control, and disparities.

BACKGROUND: Medication nonadherence is a barrier to hypertension control. The Centers for Disease Control and Prevention recommends prescribing 90-day fills for maintenance medications yet antihypertensives are often dispensed as 30-day fills. Our objectives were to examine how often patients receive 30-day supplies of medication despite prescriptions for longer duration and to examine the effect of medication fill duration on adherence and hypertension control. METHODS: We conducted a retrospective cohort study of pediatric patients with hypertension over a 3-year period. For each patient, days prescribed per fill were compared to days dispensed per fill using pharmacy reports and insurance claim data. Proportion of Days Covered (PDC) was calculated to estimate adherence. Hypertension control was determined by provider assessment of control and blood pressure measurement at the final visit. RESULTS: Final cohort included 449 patients. A total of 70% had at least one prescription for ≥ 90 days but only 37% had at least one dispense for ≥ 90 days. There was no difference in the likelihood of being prescribed a 90-day fill by insurance type (public vs. private); however, patients with public insurance were less likely to be dispensed a 90-day fill (OR = 0.068, p < 0.001). Patients who received 90-day fills had better adherence (median PDC 77.5% vs. 58.1%, p < 0.001) and were more likely to have hypertension control based on provider assessment. CONCLUSIONS: Longer fill duration is associated with improved adherence and hypertension control. Patients with public insurance are markedly less likely to be dispensed 90-day fills, a modifiable barrier to improving adherence.

School-Based Telemedicine for Hypertension Management in Urban Adolescents.

PURPOSE: The aim of this study is to determine if hypertensive adolescents from impoverished neighborhoods in Rochester, New York have improved blood pressure (BP) control with the use of school-based telemedicine. METHODS: Adolescents receiving antihypertensive medication had monthly study telemedicine visits at school. BP was measured by a telehealth clinical assistant (CTA) at the school using standard procedures, followed in real time by a teleconferencing visit with the study physician. RESULTS: Six participants were enrolled, and all completed school-based telemedicine visits prior to school closure due to the SARS-CoV-2 pandemic. Mean systolic and diastolic BP at baseline were 139 ± 5 and 75 ± 8 mmHg. All six participants had significant improvement in their blood pressure (final school mean BPs, 127 ± 4 and 67 ± 5 mmHg; systolic, baseline vs. final, p = .003). DISCUSSION: In this pilot study, adolescents with very high levels of neighborhood disadvantage had consistent adherence with school-based telemedicine and significant improvement in hypertension (HTN) control.

Case report and review of the literature: Successful transition from acute continuous veno-venous hemodiafiltration therapy to chronic peritoneal dialysis in a chronically ventilated child with hypoplastic left heart syndrome following fontan.

Fontan palliation depends on low pulmonary vascular resistance in order to maintain pulmonary blood flow and adequate oxygenation. This physiology results in higher central venous pressures with limited renal perfusion pressure and cardiac output. Positive pressure ventilation with mechanical ventilation increases intrathoracic pressure and raises central venous pressure and can further limit pulmonary and renal perfusion. Fluid removal with intermittent hemodialysis can be challenging in Fontan patients and can cause intolerable hypotension, however the increased abdominal filling pressures during peritoneal dialysis dwells can exacerbate systemic venous hypertension seen in Fontan patients and threaten adequate pulmonary blood flow and cardiac output. Successful transition to peritoneal dialysis in a chronically ventilated patient with hypoplastic left heart syndrome, end-stage renal disease and Fontan physiology has not been described. We present details outlining the successful transition across multiple modalities of renal replacement therapy to assist other teams faced with similar challenges in chronically ventilated Fontan patients with end-stage renal disease.

Blood pressure in children with sickle cell disease is higher than in the general pediatric population.

BACKGROUND: Sickle cell disease (SCD) is associated with an increased risk of cardiovascular disease that may be due to a variety of possible risk factors, including abnormal blood pressure. Blood pressure (BP) of children and adolescents with SCD has been reported to be lower compared to the BP of the general pediatric population. METHODS: To confirm this prior observation, we compared reference BP values for children with SCD with reference BP values of the general pediatric population. We hypothesized that children with SCD do not have lower BPs than children without SCD. RESULTS: Systolic BP differed for both males and females, over the different age groups between pediatric subjects with and without SCD. Systolic BP was higher in children with SCD, in both obese and non-obese populations. Diastolic BP did not differ between the groups. CONCLUSIONS: Our analysis demonstrated that systolic BP values are indeed higher in children with SCD than in the general pediatric population. This finding is consistent with the most recent literature showing abnormal BP patterns in the SCD pediatric population utilizing 24-hour BP monitoring devices. This is an important step for recognizing abnormal BP as a risk factor for cardio- and neurovascular events in SCD.

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.

Cardiovascular Risk Factors and Target Organ Damage in Adolescents: The SHIP AHOY Study.

BACKGROUND: Development of cardiovascular disease in adults has been directly linked to an adverse metabolic phenotype. While there is evidence that development of these risk factors in childhood persists into adulthood and the development of cardiovascular disease, less is known about whether these risk factors are associated with target organ damage during adolescence. METHODS: We collected data from 379 adolescents (mean age 15.5, 60% male) with blood pressure between the 75th and 95th percentile to determine if there is a metabolic phenotype that predicts cardiovascular changes (left ventricular mass, systolic and diastolic function, pulse wave velocity, and renal function). We determined the number of risk factors for cardiovascular disease (hypertension, dyslipidemia, obesity, and insulin resistance) present in each participant. Generalized linear models were constructed to determine if the number of cardiovascular risk factors (CVRFs) were associated with measures of target organ damage. RESULTS: The number of CVRFs present were associated with statistically significant differences in increased left ventricular mass index, increased pulse wave velocity, decreased peak longitudinal strain, urine albumin to creatine ratio and echocardiographic parameters of diastolic dysfunction. Generalized linear models showed that dyslipidemia and insulin resistance were independently associated with markers of diastolic dysfunction (P ≤ .05) while increased blood pressure was associated with all makers of target organ damage (P ≤ .03). CONCLUSIONS: These data suggest the of the number of CVRFs present is independently associated with early changes in markers of target organ damage during adolescence.

Overview of the findings and advances in the neurocognitive and psychosocial functioning of mild to moderate pediatric CKD: perspectives from the Chronic Kidney Disease in Children (CKiD) cohort study.

The Chronic Kidney Disease in Children (CKiD) prospective cohort study was designed to address the neurocognitive, growth, cardiovascular, and disease progression of children and adolescents with mild to moderate CKD. The study has had continuous funding from NIDDK for 17 years and has contributed significant advances in pediatric CKD. The goals of this educational review are threefold: (1) to provide an overview of the neurocognitive and psychosocial studies from CKiD to date; (2) to provide best practice recommendations for those working with the neurocognitive and psychosocial aspects of pediatric CKD based on CKiD findings; and (3) to help chart future goals and directives for both research and clinical practice. This collection of 22 empirical studies has produced a number of key findings for children and adolescents with mild to moderate CKD. While various studies suggest a relatively positive presentation for this population as a whole, without evidence of significant impairment or deterioration, findings do indicate the presence of neurocognitive dysfunction, emotional-behavioral difficulties, and lower quality of life for many children with CKD. These findings support the promotion of best practices that are accompanied by additional future clinical and research initiatives with this patient population.

Magnetic Resonance Imaging in Childhood Primary Hypertension: Potential in the Study of Cognitive Outcomes.

Primary hypertension in youth and young adulthood is associated with decreased neurocognitive test performance both in midlife and during youth itself, leading to concern of subsequent cognitive decline and dementia in later life. The early vascular effects of hypertension in youth are likely involved in the pathogenesis of hypertensive target organ damage to the brain, but the potential impact of antihypertensive treatment from youth on subsequent cognitive health is not known. This review will highlight the need to answer the question of whether treatment of hypertension from early in life would slow cognitive decline in adulthood, and will then outline, for the nonneurologist, magnetic resonance imaging techniques potentially useful in the study of the pathogenesis of decreased cognition in hypertensive youth and for use as potential biomarkers for early antihypertensive treatment interventions.

Hypertension and childhood stroke.

Cerebrovascular disease (stroke) is one of the ten leading causes of death in children and adolescents. Multiple etiologies, from arteriopathies to prothrombic states, can cause stroke in youth. In adult stroke, hypertension has been shown to be the single most important modifiable risk factor. Although hypertension has not been strongly identified as a risk factor in childhood stroke to date, there is preliminary evidence that suggests that hypertension may also be associated with stroke in children. In this review, we summarize the literature that may link hypertension to stroke in the young. We have identified a series of barriers and limitations in the fields of pediatric hypertension and pediatric neurology that might explain why hypertension has been overlooked in childhood stroke. We suggest that hypertension may be a relevant risk factor that, alone or in combination with other multiple factors, contributes to the development of stroke in children. Currently, there are no consensus guidelines for the management of post-stroke hypertension in children. Thus, we recommend that blood pressure be assessed carefully in every child presenting with acute stroke in order to better understand the effects of hypertension in the development and the outcome of childhood stroke. We suggest a treatment algorithm to help practitioners manage hypertension after a stroke.

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.

Bicarbonate, blood pressure, and executive function in pediatric CKD-is there a link?

BACKGROUND: In adult chronic kidney disease (CKD), metabolic acidosis is associated with diminished cognition, notably executive function (EF). Data from the Chronic Kidney Disease in Children (CKiD) study demonstrate a risk for impairment of EF, a finding associated with heightened blood pressure variability (BPV). We sought to determine whether low serum bicarbonate is also associated with performance on tests of EF in pediatric CKD and to investigate potential interaction with BPV. METHODS: CKiD participants with serum bicarbonate, blood pressure, and selected cognitive measurements available were evaluated. An EF summary score was derived from scores on the Delis-Kaplan Executive Function System, Conners' Continuous Performance Test, and Digit Span Backwards subtest from the Wechsler Intelligence Scale for Children-IV-Integrated. Parents completed the Behavioral Rating Inventory of Executive Function (BRIEF) to yield a Global Executive Composite (GEC) score. Linear mixed models with bicarbonate and hypertension as predictors and linear regression with bicarbonate and BPV were used to predict EF level. RESULTS: Data were available for 865 children. Twenty-two percent had low bicarbonate (CO2 ≤ 20 mmol/L) at baseline. On multivariate analysis, there was no relationship between bicarbonate, hypertension, and EF. There was no significant CO2×hypertension interaction found. A significant interaction (p = 0.01) between high CO2 (≥ 26 mmol/L) and BPV was detected in the model with GEC as the EF outcome, indicating that while higher BPV was associated with worse EF in the low and normal CO2 groups, higher BPV was associated with better EF in the high CO2 group. CONCLUSIONS: Our analyses revealed an interaction between one measure of BPV and low bicarbonate on neurocognition in pediatric CKD, suggesting a potential role for control of both bicarbonate and blood pressure in preserving cognition in early CKD. Further research is needed to confirm and further define this association.

A longitudinal examination of parent-reported emotional-behavioral functioning of children with mild to moderate chronic kidney disease.

BACKGROUND: Children with mild to moderate chronic kidney disease (CKD) are at increased risk for deficits in neurocognition. Less is known about how CKD affects emotional-behavioral functioning in this population. METHODS: Parent ratings of emotional-behavioral functioning at baseline and over time were examined for 845 children with mild to moderate CKD using the Behavior Assessment System for Children, Second Edition Parent Rating Scales (BASC-2 PRS). Associations with demographic and disease-related predictors were also examined. RESULTS: Children with mild to moderate CKD had parent-reported emotional-behavioral functioning largely within normal limits, at baseline and over time. The proportion with T-scores at least 1 SD above the mean was 24% for Internalizing Problems and 28% for Attention Problems. A greater proportion of participants scored lower than expected (worse) on scales measuring adaptive skills (25%). Persistent hypertension predicted attention problems (ß = 1.59, 95% CI = 0.24 to 2.94, p < 0.02) and suggested worse behavioral symptoms (ß = 1.36, 95% CI = - 0.01 to 2.73, p = 0.05). Participants with proteinuria at baseline, but not at follow-up, had fewer attention problems than participants whose proteinuria had not resolved (ß = - 3.48, CI = - 6.79 to - 0.17, p < 0.04). Glomerular diagnosis was related to fewer (ß = - 2.68, 95% CI = - 4.93 to - 0.42, p < 0.02) internalizing problems. CONCLUSIONS: Although children with CKD generally have average emotional-behavioral parent ratings, a notable percentage of the population may be at risk for problems with attention and adaptive behavior. Providers working with this population should facilitate psychosocial referrals when indicated.

Increased history of ischemic stroke and decreased neurocognitive performance in children with chronic kidney disease.

BACKGROUND: This study aimed to determine stroke incidence and assess the association between stroke and neurocognitive functioning in children with chronic kidney disease (CKD). METHODS: Data was derived from the Chronic Kidney Disease in Children (CKiD) cohort study. Stroke incidence was calculated after confirming self-reports of stroke occurrence by chart review. Each participant with stroke was matched with three stroke-free participants and performance on selected neurocognitive measures was compared. Wilcoxon rank-sum tests were used to compare neurocognitive test scores. Effect size (ES) was estimated using a modified version of Cohen's U3 metric that measures the excess percentage of the stroke group worse than the median of the control group. RESULTS: Of 891 subjects, five (0.56%) had a confirmed stroke prior to study entry. Median time at risk was 15.7 years [interquartile range, 12.5-18.4]. Estimated incidence rate of history of stroke was 36.8 per 100,000 children per year (95% confidence interval 15.3, 88.5). Controls and subjects with stroke were similar in age, CKD duration, race, and maternal education. ES for many of the neurocognitive comparisons was moderate to large. Subjects in the CKID cohort with a history of stroke had lower scores on spatial span reverse, spatial span forward, and design fluency, and worse parent ratings on BRIEF Metacognition Index compared to a matched sample of children with CKD without stroke. CONCLUSIONS: Children with CKD have an increased incidence of prior ischemic stroke compared to the general pediatric population. A stroke history was associated with poorer performance on neurocognitive measures. Graphical abstract.

Función cognitiva e hipertensión arterial en niños y adolescentes / Cognitive function and arterial hypertension in children and adolescents

Los jóvenes con hipertensión arterial pueden manifestar efectos adversos en órganos blanco como el corazón y la vasculatura, incluyendo hipertrofia ventricular izquierda, aumento de la rigidez arterial y aumento del grosor de la carótida. También existe evidencia reciente de efectos adversos debido a hipertensión en el cerebro, hallazgo con implicancias significativas del impacto de la hipertensión arterial primaria en la cognición, tanto durante la infancia como a lo largo de la vida. En los últimos 15 años, estudios de bases de datos y estudios uni y multicéntricos han evidenciado que la presión arterial elevada en niños y adolescentes se asocia con un menor rendimiento en las pruebas neurocognitivas durante la juventud. Se presenta un resumen de la literatura sobre el efecto de la hipertensión arterial en la neurocognición en niños y jóvenes, así como también se analizan posibles mecanismos. El hallazgo de un rendimiento más bajo en las pruebas neurocognitivas en jóvenes hipertensos sugiere que el tratamiento de la hipertensión arterial en la adolescencia podría representar una oportunidad para mejorar el deterioro posterior y, por lo tanto, mejorar la salud cognitiva futura

Youth with hypertension can manifest adverse target-organ effects on the heart and vasculature, including left ventricular hypertrophy, increased arterial stiffness, and increased carotid thickness. There is emerging evidence for hypertensive adverse effects on the brain as well, findings with significant implications for the impact of primary hypertension on cognition both during childhood and later in life. Over the past 15 years, database, single-center, and multicenter studies have provided evidence that elevated BP in children and adolescents is associated with lower performance on neurocognitive testing during youth itself. In this review, we summarize the literature on the effect of hypertension on neurocognition in youth as well as review possible mechanisms of altered cognition. The finding of lower neurocognitive test performance in hypertensive youth suggests that treatment of hypertension from adolescence may represent an opportunity to ameliorate subsequent cognitive decline and thereby improve downstream cognitive health

Ambulatory blood pressure monitoring tolerability and blood pressure status in adolescents: the SHIP AHOY study.

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) provides a more precise assessment of blood pressure (BP) status than clinic BP and is currently recommended in the evaluation of elevated BP in children and adolescents. Yet, ABPM can be uncomfortable for patients and cumbersome to perform. OBJECTIVE: Evaluation of the tolerability to ABPM in 232 adolescent participants (median age: 15.7 years, 64% white, 16% Hispanic, 53% male) in the Study of Hypertension In Pediatrics Adult Hypertension Onset in Youth and its potential effects on ABPM results. PARTICIPANTS AND METHODS: Ambulatory BP status (normal vs. hypertension) was determined by sex and height-specific pediatric cut-points. Participants were asked to rank their wake and sleep tolerability to ABPM from 1 (most tolerant) to 10 (least tolerant); those with tolerability score of at least 8 were considered ABPM intolerant. RESULTS: Forty-three (19%) participants had wake ambulatory hypertension (HTN), 42 (18%) had sleep ambulatory HTN, and 64 (28%) had overall (wake and/or sleep) ambulatory HTN. Forty (17%) participants were intolerant to ABPM during wake hours and 58 (25%) were intolerant during sleep. ABPM intolerance during wake (but not sleep) hours was independently associated with wake (odds ratio: 2.34, 95% confidence interval: 1.01-5.39) and overall (odds ratio: 2.94, 95% confidence interval: 1.21-7.18) ambulatory HTN. CONCLUSION: Poor tolerability to ABPM is associated with a higher prevalence of ambulatory HTN in adolescents, and should be taken into consideration at time of ABPM interpretation.

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.