Ambulatory blood pressure monitoring and neurocognitive function in children with primary hypertension.

BACKGROUND: Children with primary hypertension have been reported to have diminished scores in measures of cognition. However, little is known about the relative correlation between office and ambulatory blood pressure (BP) and neurocognitive test performance, and whether short-term BP variability is associated with decreased neurocognitive function. We sought to determine whether ambulatory BP monitoring (ABPM) was more strongly associated with neurocognitive test performance compared with office BP, and whether increased short-term BP variability was associated with lower neurocognitive scores. METHODS: Seventy-five subjects ages 10-18 years, with untreated primary hypertension, and 75 matched normotensive controls completed neurocognitive testing. All subjects had office BP and ABPM prior to neurocognitive testing. RESULTS: On multivariate analyses, there was no significant association between office BP and neurocognitive tests. However, several ABPM parameters were significantly associated with neurocognitive test scores in the lower quartile, in particular 24 h SBP load and wake systolic blood pressure (SBP) index [Rey Auditory Verbal learning Test (RAVLT) List A Trial 1, 24 h SBP load, odds ratio (OR) = 1.02, wake SBP index, OR = 1.06; List A Total, 24 h SBP load, OR = 1.02, wake SBP index, OR = 1.06; Short Delay Recall, wake SBP index, OR = 1.06; CogState Maze delayed recall, 24 h SBP load, OR = 1.03, wake SBP index, OR = 1.08; Grooved Pegboard, 24 h SBP load, OR = 1.02; all p < 0.05]. In contrast, short-term BP variability measures were not associated with neurocognitive test performance. CONCLUSIONS: ABPM is superior to office BP in distinguishing hypertensive youth with lower neurocognitive test performance.

Neurocognitive Function in Children with Primary Hypertension after Initiation of Antihypertensive Therapy.

OBJECTIVE: To determine the change in neurocognitive test performance in children with primary hypertension after initiation of antihypertensive therapy. STUDY DESIGN: Subjects with hypertension and normotensive control subjects had neurocognitive testing at baseline and again after 1 year, during which time the subjects with hypertension received antihypertensive therapy. Subjects completed tests of general intelligence, attention, memory, executive function, and processing speed, and parents completed rating scales of executive function. RESULTS: Fifty-five subjects with hypertension and 66 normotensive control subjects underwent both baseline and 1-year assessments. Overall, the blood pressure (BP) of subjects with hypertension improved (24-hour systolic BP load: mean baseline vs 1 year, 58% vs 38%, P < .001). Primary multivariable analyses showed that the hypertension group improved in scores of subtests of the Rey Auditory Verbal Learning Test, Grooved Pegboard, and Delis-Kaplan Executive Function System Tower Test (P < .05). However, the control group also improved in the same measures with similar effects sizes. Secondary analyses by effectiveness of antihypertensive therapy showed that subjects with persistent ambulatory hypertension at 1 year (n = 17) did not improve in subtests of Rey Auditory Verbal Learning Test and had limited improvement in Grooved Pegboard. CONCLUSIONS: Overall, children with hypertension did not improve in neurocognitive test performance after 1 year of antihypertensive therapy, beyond that also seen in normotensive controls, suggesting improvements with age or practice effects because of repeated neurocognitive testing. However, the degree to which antihypertensive therapy improves BP may affect its impact upon neurocognitive function.

Neurocognitive Function in Children with Primary Hypertension.

OBJECTIVE: To compare neurocognitive test performance of children with primary hypertension with that of normotensive controls. STUDY DESIGN: Seventy-five children (10-18 years of age) with newly diagnosed, untreated hypertension and 75 frequency-matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. Subjects completed tests of general intelligence, attention, memory, executive function, and processing speed. Parents completed rating scales of executive function and the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (PSQ-SRBD). RESULTS: Hypertension and control groups did not differ significantly in age, sex, maternal education, income, race, ethnicity, obesity, anxiety, depression, cholesterol, glucose, insulin, and C-reactive protein. Subjects with hypertension had greater PSQ-SRBD scores (P = .04) and triglycerides (P = .037). Multivariate analyses showed that hypertension was independently associated with worse performance on the Rey Auditory Verbal Learning Test (List A Trial 1, P = .034; List A Total, P = .009; Short delay recall, P = .013), CogState Groton Maze Learning Test delayed recall (P = .002), Grooved Pegboard dominant hand (P = .045), and Wechsler Abbreviated Scales of Intelligence Vocabulary (P = .016). Results indicated a significant interaction between disordered sleep (PSQ-SRBD score) and hypertension on ratings of executive function (P = .04), such that hypertension heightened the association between increased disordered sleep and worse executive function. CONCLUSIONS: Youth with primary hypertension demonstrated significantly lower performance on neurocognitive testing compared with normotensive controls, in particular, on measures of memory, attention, and executive functions.

Immunogenicity of Human Papillomavirus Recombinant Vaccine in Children with CKD.

BACKGROUND AND OBJECTIVES: There is a disproportionate burden of human papillomavirus (HPV) -related genital tract disease in patients with CKD and kidney transplantation; therefore, the potential effect of the quadrivalent HPV vaccine (Gardasil; Merck GmbH, Darmstadt, Germany) is profound. Immune abnormalities associated with CKD and immunosuppression may prevent optimal vaccine response. Our objective was to determine antibody response to the HPV vaccine in adolescent girls with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This cohort study conducted from 2008 to 2012 included 57 girls aged 9-21 years old with CKD (n=25), on dialysis (n=9), or with status postkidney transplantation (n=23) who received the standard three-dose vaccine series of the HPV vaccine recruited from two pediatric nephrology clinics. Antibody levels to HPV genotypes 6, 11, 16, and 18 were measured before vaccine dose 1 (baseline), <12 months after vaccine dose 3 (blood draw 2), and ≥12 months after vaccine dose 3 (blood draw 3). Seropositivity was defined as antibody level above an established threshold for each HPV genotype. Not all participants completed three blood draws. RESULTS: Antibody response to all four HPV genotypes was 100% in the CKD and dialysis groups with samples drawn at <12 and ≥12 months after dose 3 of the HPV vaccine. Among patients with transplants, the percentages of patients achieving seropositivity were significantly lower at blood draw 2 for HPV genotypes 6 (63.6%; P=0.003), 11 (63.6%; P=0.003), and 18 (72.7%; P=0.02) and blood draw 3 for HPV genotypes 6 (62.5%; P=0.02), 11 (50%; P=0.001), 16 (75%; P=0.04), and 18 (50%; P=0.001). CONCLUSIONS: Antibody response to the quadrivalent recombinant HPV vaccine was robust and sustained in girls and young women with CKD and on dialysis. A less robust response to the vaccine was observed among those with a kidney transplant. Additional study is needed to determine if vaccination before kidney transplantation or an alternative vaccination regimen would benefit transplant recipients.

Increased prevalence of elevated blood pressures in HIV-infected children, adolescents and young adults.

BACKGROUND: HIV-infected children and young adults have cardiovascular disease risk factors reflecting chronic infection and the effects of combination antiretroviral (ARV) therapy. We thus sought to characterize the prevalence of and risk factors for high blood pressure (HBP) in this population. METHODS: Retrospective chart review classified subjects aged 2-25 years based on a single clinic blood pressure (BP) reading as normal BP, pre-HBP or HBP. Variables suspected to contribute to elevated BP were compared including body mass index, tobacco use, medical comorbidities, ARV or other medication use, dyslipidemia, ethnicity and family history. RESULTS: In all, 47 of 266 subjects (18%) were found to have HBP. Among children and adolescents aged 2-17 years, 21 of 107 (20%) had HBP. Comorbidities believed to elevate BP, such as polycystic ovarian syndrome, obstructive sleep apnea or cocaine exposure, were significant risk factors for elevated BP, with 35% of subjects with these comorbidities having HBP, compared with 16% of subjects without (P = 0.01). Male gender and tobacco use were also risk factors associated with elevated BPs. HBP was more common in overweight subjects (26%) than not overweight (15%) but did not reach statistical significance (P = 0.15). ARV medication use and higher HIV-1 RNA were not associated with HBP. CONCLUSIONS: Our finding of 20% prevalence of HBP in a cohort of HIV-infected children represents a potentially alarming figure. The explanation for this finding is unclear, but even if it is because of comorbid conditions, the life-long cardiovascular risks associated with HIV infection and its management mandate the need for closer monitoring and possibly treatment of elevated BP in this population.

Sleep disordered breathing as measured by SRBD-PSQ and neurocognition in children with hypertension.

BACKGROUND: Cognitive test performance is decreased in hypertensive adults and children, a finding postulated to represent early target-organ damage to the brain. Hypertensive children are often obese, a comorbidity associated with sleep disordered breathing (SDB), itself associated with cognitive problems; potentially confounding the relation between hypertension (HTN) and neurocognition. Our objective was to determine the association between SDB as measured by a scale and questionnaire score and neurocognition among participants enrolled in an ongoing multicenter study of cognition in children with HTN. METHODS: Subjects completed laboratory-based neurocognitive tests. Parents and subjects completed rating scales of executive function, mood, and behavior problems. Parents completed the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (SRBD-PSQ). RESULTS: To date, 38 HTN subjects and 34 control subjects have completed neurocognitive testing and the SRBD-PSQ. Median SRBD-PSQ scores were similar between groups but the HTN group had a higher percentage of subjects with SRBD-PSQ scores in the range suggestive of obstructive sleep apnea (26% vs. 6%, P = 0.03). Overall, higher SRBD-PSQ scores were not significantly associated with worse performance on laboratory-based measures of executive function and other cognitive domains but were significantly associated with worse scores on rating scales of executive function as well as mood and behavior problems. CONCLUSIONS: A larger proportion of children with HTN had scores suggestive of SDB. The results underscore the importance of using a multi-method approach in the assessment of cognition and adjusting for potential confounding effects of SDB in studies of cognition in hypertensive children.

Neonatal hypertension.

The incidence of neonatal hypertension (HTN) remains low, at less than 2%, and its etiology is varied. Strict definitions of HTN in neonates are unavailable, and the decision to treat is based on opinion rather than evidence. More studies are needed to define normal blood pressure in neonates and to refine current reference values, thus permitting a better definition of HTN. Most causes of neonatal HTN, the most common of which seems to be renovascular disease, are determined by history and basic clinical investigations. Treatment is guided by clinical judgment and expert opinion, given the limited number of clinical trials.

Aliskiren, the first direct renin inhibitor: assessing a role in pediatric hypertension and kidney diseases.

This article provides a review of the role of aliskiren, a direct renin inhibitor, in pediatric hypertension and kidney diseases. Among the many mechanisms involved in regulating blood pressure, the renin-angiotensin-aldosterone system (RAAS) plays a major role. Additionally, the RAAS has been identified as a contributing factor to cardiovascular and renal diseases for more than three decades. The potential benefits of inhibiting the RAAS by aliskiren alone or in combination with other RAAS blockers (ACEIs, ARBs) seem to be theoretically promising. However, caution should be exercised in treating children, especially in those with significant chronic kidney disease until there is more evidence regarding the safety and efficacy of this new drug in the pediatric population from ongoing clinical trials.

A multicenter study of neurocognition in children with hypertension: methods, challenges, and solutions.

Hypertensive adults demonstrate decreased performance on neurocognitive testing compared with that of normotensive controls. There is now emerging, preliminary evidence that children with hypertension also manifest neurocognitive differences when compared with normotensive controls, findings postulated to potentially represent early signs of hypertensive target organ damage to the brain. However, reports in children to date have been limited to database and single-center studies. We have established an ongoing, prospective, multicenter study of neurocognition in children with primary hypertension. This article outlines the study methods, with particular attention to the unique challenges in this area of clinical research. We highlight aspects of the study design that are specifically designed as solutions to these challenges.

What is the optimal first-line agent in children requiring antihypertensive medication?

There has been an evolution in the understanding of the treatment of hypertension in children and adolescents over the past decade. This has been fueled in part by the increased attention paid to the clinical problem, given the increasing numbers of children and adolescents being diagnosed with this condition. There has also been a growing number of clinical trials performed and completed that demonstrate the blood pressure (BP)-lowering effects of antihypertensives and the side effect profiles of these medications, and that has led to FDA-labeling of many antihypertensive medications for use in children and adolescents. However, none of these trials has provided definitive data on the optimal first line agent for this patient population. Clinical experience and other approaches discussed in this review are still necessary to guide treatment of hypertension in the young. The quest for the optimal antihypertensive agent is just beginning, and it is going to take some extraordinary effort to reach that goal.

Blood pressure variability, prehypertension, and hypertension in adolescents.

Medical conditions diagnosed during adolescence may have long term impacts on the health of an individual. As a result, identifying cardiovascular risk factors earlier in life such as prehypertension (pre-HTN) and hypertension (HTN) can have significant benefits across an individual's lifespan. Diagnosing elevated blood pressure (BP) during adolescence can be difficult, partially due to the natural variability that occurs during this period of life. Levels of BP that define adolescent prehypertension/hypertension are provided as well as an abridged review of BP variability across research groups. Strategies for BP management of adolescents are considered, with the primary focus on nonpharmacologic interventions.

Obesity and the role of lifestyle and dietary intervention in the management of pediatric hypertension.

As the prevalence of hypertension in children and adolescents increases within the context of the epidemic of obesity, it is important to recognize that while hypertension may be secondary to an underlying disorder, one must not overlook the impact that overweight and obesity have on the condition. While considering options for the overall management of hypertension in the context of overweight and obesity one should incorporate strategies that focus on therapeutic lifestyle changes, as discussed in the Fourth Report on Blood Pressure in Children and Adolescents. The strategies that will be discussed in this article include weight loss, exercise and dietary interventions. These treatment strategies require a great deal of motivation on the part of the patient, the patient's family and the patient's care providers. Not all strategies will be effective for every individual, but to some extent all patients being treated for hypertension should incorporate elements of therapeutic lifestyle changes into their treatment regimen.