Book Description

PURPOSE: To review the evidence about screening for high blood pressure in children and adolescents to delay the onset of or reduce adverse health outcomes related to high blood pressure. DATA SOURCES: MEDLINE, Embase, International Pharmaceutical Abstracts, the Cochrane Library, and trial registries through September 3, 2019; bibliographies from retrieved articles, outside experts, and surveillance of the literature through October 6, 2020. STUDY SELECTION: Two investigators independently selected studies using a priori defined inclusion and exclusion criteria. For this update, we included studies of screening for primary and secondary hypertension in asymptomatic children and adolescents. For benefits and harms of treatments or the association between hypertension in children and adolescents and intermediate outcomes in adults, we included participants with primary or secondary hypertension or elevated blood pressure. We selected studies that evaluated the diagnostic accuracy of blood pressure measurements in children and adolescents within primary care settings. We also included epidemiological studies that assessed the association between high blood pressure in children and adolescents and hypertension and other intermediate outcomes in adults. We included intermediate outcomes only if they were closely related to hypertension (e.g., left ventricular hypertrophy, urinary albumin excretion, retinal vascular changes, and intima media thickness). For treatment of hypertension, we selected controlled trials of pharmacological agents, lifestyle interventions, or combination treatments. We excluded studies with poor methodological quality and studies conducted in developing countries. DATA EXTRACTION AND ANALYSIS: One investigator extracted data and a second checked accuracy. Two reviewers independently rated methodological quality for all included studies using predefined criteria. Because data were insufficient for meta-analyses, we qualitatively synthesized findings for each key question. DATA SYNTHESIS: We included 42 studies (43 publications). We did not identify any studies directly evaluating health benefits or harms of screening. We also did not find studies assessing whether effective treatment of abnormal blood pressure during childhood has an impact on hypertension and other intermediate outcomes during adulthood. Furthermore, we did not find any studies that addressed screening for secondary hypertension in asymptomatic children. One fair study (n=247) assessed the diagnostic test accuracy of six office-based blood pressure measurements, 1 to 2 weeks apart, compared with ambulatory blood pressure monitoring as the reference standard. Office-based blood pressure measurements used recommendations of the Fourth Report as thresholds. Using systolic blood pressure (SBP) at the 90th percentile as a cutoff for abnormal blood pressure, the sensitivity of office-based measurements was 81.6 percent (confidence interval [CI] not reported) with a specificity of 70.3 percent (CI not reported). Twenty studies on data from nine national and international cohorts evaluated the association between high blood pressure in childhood and hypertension or other intermediate outcomes during adulthood. Despite substantial heterogeneity, studies consistently reported associations between abnormal blood pressure in childhood and abnormal blood pressure in adulthood. The strength of associations varied across studies (odds ratios [ORs] ranged from 1.1 to 4.5, relative risk [RR] ranged from 1.45 to 3.60, hazard ratios [HRs] ranged from 2.8 to 3.2; duration of followup ranged from 10 to 33 years). Studies also reported associations between abnormal blood pressure during childhood and carotid intima-media thickness (OR: 1.24, 95% CI, 1.13 to 1.37 [mean duration of followup was 25 years]; HRs ranged from 2.03 to 3.07 [duration of followup ranged from 10 to 21 years]; correlation coefficients ranged from 0.04 to 0.16 [duration of followup ranged from 21 to 31 years]), left ventricular hypertrophy (ORs ranged from 1.30 to 1.59, mean duration of followup was 25 years; HRs ranged from 1.92 to 3.41; duration of followup ranged from 10 to 21 years), and microalbuminuria (regression coefficients ranged from 0.016 to 0.315; mean duration of followup was 16.1 years). Twenty randomized, controlled trials (RCTs) and a meta-analysis assessing treatments for hypertension in children and adolescents met inclusion criteria. The majority of studies excluded children with known secondary hypertension. Thirteen fair-quality placebo-controlled RCTs and one meta-analysis evaluated the efficacy of various pharmacological treatments. All studies reported greater reductions of SBP and diastolic blood pressure (DBP) measurements in participants who received pharmacological treatments compared with those treated with placebo. The magnitude of reductions, however, varied, and not all differences reached statistical significance. Pooled reductions of SBP were −4.38 mmHg (95% CI, −2.16 to −7.27) for angiotensin-converting enzyme (ACE) inhibitors, −3.07 mmHg (95% CI, −1.44 to −4.99) for angiotensin receptor blockers (ARBs), −3.20 mmHg (95% CI, +2.23 to −8.69) for beta blockers, −3.10 mmHg (95% CI, +0.45 to −6.52) for calcium channel blockers, and −0.12 mmHg (95% CI, +3.46 to −3.69) for mineralocorticoid receptor antagonists. Followup of studies was limited to 2 to 4 weeks. One fair-quality trial, conducted from 1979 to 1981 in the United States and using a combination of a pharmacological treatment (low-dose propranolol/chlorthalidone) and lifestyle interventions (dietary and exercise modifications for children and parents), reported a statistically significant reduction of SBP (−7.6 mmHg) and DBP (−6.9 mmHg) after 6 months. A DASH (Dietary Approaches to Stop Hypertension) −type diet (high in fruits, vegetables, and low-fat dairy foods) achieved statistically significant reductions in SBP (−2.2 mmHg) and DBP (−2.8 mmHg) in a completers-only analysis of one fair-quality RCT. The effect did not last beyond the intervention period. Two fair-quality RCTs assessing physical exercise reported statistically significant decreases in SBP after 3 and 8 months (−8.3 and −4.9 mmHg, respectively) compared with lifestyle as usual. Only the study lasting 8 months reported a significant decrease in DBP (−3.8 mmHg vs. not reported). Based on evidence from three fair-quality trials, a low-sodium diet and progressive muscle relaxation did not achieve any significant or clinically relevant changes in SBP or DBP. Regarding harms of treatments, six fair-quality RCTs reported similar risks of adverse events between various pharmacological treatments (beta blocker, calcium channel blockers, angiotensin-converting enzyme, inhibitors or angiotensin receptor blockers) and placebo. The duration of trials, however, was limited to 2 to 4 weeks. One fair-quality RCT reported similar risks for adverse events between a combination of pharmacotherapy and lifestyle interventions and a control group without treatment over 6 months. LIMITATIONS: Only English-language studies were included. No direct evidence for the benefits or harms of screening was identified. In addition, the indirect evidence pathway from screening to improvement of health outcomes is scarce, of limited applicability, or entirely missing for some steps of the pathway. The evidence on diagnostic accuracy was limited to one poor quality study. Epidemiological studies determining associations between high blood pressure in childhood and adulthood used various definitions and thresholds; the results were generally consistent in demonstrating an association, although the strength of association varied. Pharmacological treatment studies were limited to durations of 2 to 4 weeks of followup and excluded children with secondary hypertension; no evidence was available for long-term effectiveness. The mean age of children in these studies ranged between 12 and 14 years; the generalizability of results to younger children or children with secondary hypertension is unknown. Studies of treatment were generally too short and underpowered for harm outcomes. We did not assess the comparative effectiveness or harms of treatments. CONCLUSIONS: We identified no direct evidence that compared screening with no screening in asymptomatic children and adolescents. Epidemiological studies indicate an association between hypertension in childhood and adolescence and hypertension in adulthood. Large longitudinal cohort studies also provide evidence that hypertension in adolescents and young adults is associated with end-stage renal disease and mortality from cerebrovascular events during adulthood. The proportion of spontaneous resolution of hypertension in children and the long-term benefits and harms of treatment, however, remain unclear. The evidence is also inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care. Short-term pharmacological treatments appear effective and safe, but no evidence with a followup of more than 4 weeks is available. No evidence exists to determine whether screening for hypertension is effective in identifying children with secondary hypertension who are asymptomatic. Most treatment studies excluded children with secondary hypertension.