Final Research Plan

High Blood Pressure in Children and Adolescents: Screening

November 01, 2018

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

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The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment on the USPSTF Web site from June 28 to July 25, 2018.

This figure is the analytic framework depicting the eight key questions and the research approach that will guide the evidence review outlined in this research plan. In general, the figure illustrates the overarching question of whether screening for high blood pressure (i.e., persistently elevated blood pressure or hypertension) in children and adolescents delays the onset of or reduces adverse health outcomes related to high blood pressure (Key Question 1). The framework starts on the left with the patient population of interest, asymptomatic children and adolescents. Moving from left to right, the figure depicts an initial screening assessment, following which detection occurs for children and adolescents with high blood pressure (Key Question 2). Those detected to have high blood pressure will then have a diagnostic workup. Following diagnostic workup, individuals may be classified as having persistently elevated blood pressure and primary and secondary hypertension or not. The association of primary hypertension in children and adolescents and high blood pressure and other intermediate outcomes (including left ventricular hypertrophy, urinary albumin excretion, intima media thickness, and retinal vascular changes) in adults is also assessed (Key Question 4). Screening may result in harms (Key Question 3). For children and adolescents with hypertension, treatment may reduce blood pressure and other intermediate outcomes in children (Key Question 5) and adults (Key Question 6). Treatment may also reduce adverse health outcomes related to primary hypertension in adults (Key Question 7). Treatment may result in harms (Key Question 8).

*Intermediate outcomes include left ventricular hypertrophy, urinary albumin excretion (microalbuminuria), intima media thickness (measured at the carotid, femoral, or both arteries), and retinal vascular changes.

  1. Does screening for high blood pressure (i.e., persistently elevated blood pressure or hypertension) in children and adolescents delay the onset of or reduce adverse health outcomes related to high blood pressure?
  2. What is the diagnostic accuracy of screening tests for high blood pressure in children and adolescents?
  3. What are the adverse effects, such as labeling and anxiety, of screening for high blood pressure in children and adolescents?
  4. What is the association between high blood pressure in children and adolescents and high blood pressure and other intermediate outcomes in adults?
  5. What are the effectiveness of drug, nondrug, and combination interventions for treating high blood pressure in children and adolescents?
  6. What are the effectiveness of drug, nondrug, and combination interventions initiated for the treatment of high blood pressure in children and adolescents for reducing blood pressure and improving other intermediate outcomes in adults?
  7. What are the effectiveness of drug, nondrug, and combination interventions initiated for the treatment of high blood pressure in children and adolescents for reducing adverse health outcomes related to high blood pressure in adults?
  8. What are the adverse effects of drug, nondrug, and combination interventions for treating high blood pressure in children and adolescents?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the prevalence of primary and secondary hypertension in asymptomatic children and adolescents in primary care settings?
  2. What are the optimal ages at which to start screening for high blood pressure and the optimal time intervals at which to repeat screening in children and adolescents?
  3. What are the associations between intermediate outcomes related to high blood pressure in children and adolescents and health outcomes related to high blood pressure in children, adolescents, and adults?
  4. What are the effectiveness and adverse effects of drug, nondrug, and combination interventions for treating the underlying conditions of secondary hypertension in children and adolescents?

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).

  Included Excluded
Populations KQs 1–3: Asymptomatic children and adolescents ages 3–18 years, with no known diagnosis of persistently elevated blood pressure or hypertension

KQs 4–8: Studies in which all participants have persistently elevated blood pressure or hypertension*

 Pregnant adolescents; populations in which the majority of children or adolescents have high risk for developing high blood pressure and are being treated in a specialty clinic for the underlying condition (e.g., children and adolescents with obesity, neurofibromatosis, chronic kidney disease, cardiac abnormalities, specific genetic disorders)
Interventions KQs 1, 3: Screening for high blood pressure with three separate measurements, using auscultatory or oscillometric devices (based on established normative thresholds)

KQ 2: Index test consisting of at least one blood pressure measurement, using auscultatory or oscillometric devices (based on established normative thresholds)

KQs 5–8:

  • Antihypertension medications that are currently approved by the U.S. Food and Drug Administration for use in children, adolescents, or both
  • Lifestyle modifications, including diet and exercise
  • Combinations of drug and lifestyle interventions
 KQs 1, 3:
  • Screening that cannot be implemented in primary care settings
  • Screening with fewer than three separate blood pressure measurements

KQ 2:

  • Diagnostic tests not used for screening in primary care settings

KQs 5–8:

  • Interventions that treat underlying causes of secondary hypertension (these interventions will be addressed in Contextual Question 3)
  • Interventions for which treatment of high blood pressure is not the primary objective of the study (i.e., diet and physical activity interventions for weight loss or prevention of weight gain); interventions for the primary prevention of high blood pressure
Comparator KQs 1, 3: No screening

KQ 2: Diagnosis of persistently elevated blood pressure or hypertension after additional diagnostic workup (e.g., 24-hour or ambulatory blood pressure measurement)

KQs 5–8: Placebo, delayed intervention, or other inactive interventions		 KQ 2: Any reference test not specified in the inclusion criteria; studies with no reference test

KQs 5–8: Active interventions or usual care
Outcomes KQs 1, 7 (Hypertension-related outcomes):
  • Severe visual impairment
  • End-stage renal disease
  • Cardiovascular events, including ischemic heart disease and heart failure
  • Cerebrovascular events, including hemorrhagic and thrombotic stroke and hypertensive encephalopathy
  • Mortality (all-cause and disease-specific [renal disease, cardiovascular disease])

KQs 1, 5, 6 (Hypertension-related intermediate outcomes):

  • Blood pressure
  • Left ventricular hypertrophy (defined using left ventricular mass index, measures of left ventricular geometry, or both)
  • Urinary albumin excretion (microalbuminuria)
  • Intima media thickness (measured at carotid, femoral, or both arteries)
  • Retinal vascular changes

KQ 2: Measures of test accuracy (e.g., positive and negative predictive value, likelihood ratios, sensitivity, specificity, receiver operating characteristic curves)

KQ 3: Labeling, anxiety, and school absenteeism

KQ 4: Predictive and prognostic validity (e.g., positive and negative predictive value, likelihood ratios, sensitivity, specificity); measures of association (e.g., odds ratio, risk ratio, correlation or regression coefficient)

KQ 8: Harms of drug and nondrug interventions for high blood pressure

 KQ 2:
  • Correlation
  • Studies that do not provide enough data to recreate 2x2 tables to calculate sensitivity and specificity

KQs 5, 6:

  • Measures of cognitive function
  • Blood pressure variability, such as diurnal variation, or nocturnal blood pressure dipping
  • Arterial wall dysfunction, including measures of arterial stiffness, pulse wave velocity, and augmentation index
  • Metabolic measures, namely glucose tolerance or other measures of impaired glucose tolerance, insulin level, lipid profile, and homocysteine level
  • Uric acid level
  • Inflammatory markers, including C-reactive protein
  • Changes in weight or body mass index
Settings KQs 1, 3: Primary care clinics, well-child/adolescent visits, or ambulatory settings; school- or community-based screening

KQ 4: All settings

KQs 5–8: Pediatric and family practices, pediatric specialty/subspecialty clinics, inpatient or long-term care settings, emergency or urgent care facilities, or ambulatory settings; school- or community-based treatment

 KQs 1–3: Pediatric specialty/subspecialty clinics; emergency or urgent care facilities

KQs 5–8: Settings that are not comparable to or referable from primary care
Study Designs KQ 1: Randomized controlled trials, controlled clinical trials, observational studies with a comparison group (e.g., comparative cohort and case-control studies), and systematic reviews

KQ 2: Studies of diagnostic test accuracy

KQs 3, 8: Randomized controlled trials, controlled clinical trials, observational studies with a comparison group (e.g., cohort and case-control studies), and systematic reviews; if none identified, will accept uncontrolled before-after studies

KQ 4: Longitudinal cohort studies

KQs 5–7: Randomized controlled trials, controlled clinical trials, observational studies with a comparison group (e.g., large [sample size >1,000] cohort and case-control studies), and systematic reviews		  

*Definitions may vary based on prevalent guidelines at the time of the study.

The draft Research Plan was posted for public comment on the USPSTF Web site from June 28, 2018 to July 25, 2018. The USPSTF received several comments requesting that it change the language to consistently state screening for and treatment of “high blood pressure” rather than “hypertension.” As a result, the USPSTF updated the analytic framework and KQs to consistently state “high blood pressure (i.e., persistently elevated blood pressure or hypertension).” The USPSTF also adjusted the age ranges for screening to ages 3 to 18 years to align with the American Academy of Pediatrics’ recommendation.