Abstract
Purpose of Review
This review summarizes current knowledge on blood pressure in children and adolescents (youth), with a focus on primary hypertension—the most common form of elevated blood pressure in this demographic. We examine its etiology, progression, and long-term cardiovascular implications. The review covers definitions and recommendations of blood pressure classifications, recent developments in measurement, epidemiological trends, findings from observational and clinical studies, and prevention and treatment, while identifying gaps in understanding and suggesting future research directions.
Recent Findings
Youth hypertension is an escalating global issue, with regional and national variations in prevalence. While the principles of blood pressure measurement have remained largely consistent, challenges in this age group include a scarcity of automated devices that have passed independent validation for accuracy and a generally limited tolerance for ambulatory blood pressure monitoring. A multifaceted interplay of factors contributes to youth hypertension, impacting long-term cardiovascular health. Recent studies, including meta-analysis and sophisticated life-course modelling, reveal an adverse link between youth and life-course blood pressure and subclinical cardiovascular outcomes later in life. New evidence now provides the strongest evidence yet linking youth blood pressure with clinical cardiovascular events in adulthood. Some clinical trials have expanded our understanding of the safety and efficacy of antihypertensive medications in youth, but this remains an area that requires additional attention, particularly regarding varied screening approaches.
Summary
This review outlines the potential role of preventing and managing blood pressure in youth to reduce future cardiovascular risk. A global perspective is necessary in formulating blood pressure definitions and strategies, considering the specific needs and circumstances in low- and middle-income countries compared to high-income countries.
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Introduction
Cardiovascular (CV) disease can trace its origins to early life [1,2,3,4], with research suggesting that blood pressure (BP) during childhood and adolescence (youth) can have lasting CV implications. These implications include an elevated risk of adult hypertension [5, 6], target-organ damage indicating pre/subclinical CV disease or vascular ageing [7, 8], and recent findings also point to clinical CV end-points in mid-age [9, 10]. High systolic BP (SBP) was identified as the leading risk factor for CV diseases in youths and young adults aged 15–39 years, responsible for 39.4% of the age-standardized rate of disability-adjusted-life-years [11]. These findings underscore the importance of early preventive strategies and effective interventions to manage elevated BP levels in youth. While primordial prevention is broadly supported, debate continues over the best approach for managing BP levels in youth, a contention mirrored in other CV health indicators in youth, such as cholesterol [12,13,14]. Central to these debates is balancing the potential benefits of early detection and management versus the potential harms of overdiagnosis, unnecessary patient anxiety, and the long-term consequences of treatment.
Initially, our goal was to update a previous review that focused on pediatric BP and adult subclinical markers of CV disease [8]. However, in compiling this update, it became clear that a broader, more comprehensive summary might benefit the field. Consequently, this review aims to provide a current overview of BP in youth, examining its classification, measurement, prevalence and trends, and potential long-term implications for CV health. We also review evidence-based recommendations for prevention and intervention, discuss promising areas of research, identify gaps in current understanding, and suggest future research directions.
Definition of Youth Hypertension
Hypertension is categorized into primary hypertension, which arises without a clearly identifiable cause, and secondary hypertension, which results from other medical conditions affecting organs such as the kidneys, arteries, heart, or endocrine system. This review focuses on primary hypertension, with reviews on secondary hypertension available elsewhere [15, 16].
Key definitions of hypertension in youth were introduced in the 2017 American Academy of Pediatrics (AAP) [17], 2016 European Society of Hypertension (ESH) [18], and the 2004 National High Blood Pressure Education Program (referred to as the Fourth Report) [19] guidelines (Table 1). These guidelines defined hypertension in children as SBP or diastolic BP (DBP) greater-than or equal to the age-, sex-, and height-specific 95th percentile values. However, they differ on the ages at which adult thresholds are applied for adolescents. The Fourth Report uniformly apply these percentiles to youth aged 1–17 years [19], whereas the AAP guidelines recommend American adult cut-points (≥ 130/80 mmHg) starting from age 13 years [17], and the ESH guidelines recommend European adult cut-points (≥ 140/90 mmHg) from age 16 years [18]. Aligning hypertension definitions between adolescents and adults aims to facilitate a smoother transition in care, but use of the static thresholds, which may be above or below an adolescent’s 95th percentile, carries an inherent risk of misclassification and potentially missing early prevention and intervention opportunities. In the absence of outcome-based criteria and direct evidence on the benefits of early diagnosis and intervention, a cautious approach is justified, prioritizing patient safety and minimizing risks of overdiagnosis and overtreatment among adolescents. Nevertheless, the fixed cut-off of 130/80 mmHg for adolescents aged 13–17 years has shown to be comparable with the more complex percentile-based cut-offs in identifying those at risk [20].
The AAP, ESH, and Fourth Report all use normative BP values derived from United States (US) youth to establish age-, sex-, and height-specific BP percentiles. However, they differ in their inclusion criteria. The Fourth Report includes data from youth across all weight categories [19], whereas the AAP uses data only from normal-weight youth [17]. The ESH guidelines initially endorsed values from the Fourth Report [18], but the latest consensus advised shifting to the AAP’s tables for youth under 16 years [21]. The rationale for the modified BP tables is that normative BP values derived from data including youth with overweight and obesity push cut-offs to higher BP levels compared to those restricted to normal-weight youth, potentially misclassifying BP status [17].
Outside of the US, countries like China [22], India [23], and the United Kingdom (UK) [24] have established national normative BP data for youth reflecting the local demographic (summarized in Table 1). Moreover, international age-, sex-, and height-specific BP references have been constructed for youth aged 6 to 17 years across seven countries [25], although no such data exist for African youth [26]. Some guidelines, such as Hypertension Canada Guideline Committee [27], the Japanese Society of Hypertension [28], and a consensus from the European Society of Cardiology [21] recommend fixed cut-offs for some or all age-groups of children and adolescents (Table 1).
The rationale for using these fixed, and inherently simplified, cut-offs is evidence from the Bogalusa Heart Study that BP classified using fixed cut-offs (children aged 6–11 years: SBP/DBP ≥ 120/80 mmHg; adolescents aged 12–17 years: SBP/DBP ≥ 130/85 mmHg) associated with increased risk of adult hypertension and subclinical CV damage [29]. These fixed cut-offs also cross-sectionally associated with childhood markers of vascular structure and arterial stiffness in an international consortium [30, 31]. Interestingly, these two fixed cut-offs had the same utility as the percentile-based definition from the Fourth Report that encompasses up to 238 cut-offs for the 95th percentiles of BP (17 ages*2 sexes*7 height percentiles) [29], and those from the AAP guideline [30, 31]. Further, in a large sample of youth from seven countries, the height-specific 95th BP percentile values, with 22 fixed cut-offs (11 height categories in increments of 10-cm from 80 to 180 cm*2 sexes), performed best among 11 simplified methods, including the abovementioned two fixed cut-offs, having a higher positive predictive value (PPV) of ~ 90% and negative predictive value (NPV) of 100% compared with the complex cut-offs in the Fourth Report [32].
Despite the variation in hypertension definitions [17,18,19, 21, 22, 27, 28], there is consensus on the need for multiple BP measurements across repeated visits to confirm diagnosis. However, differences exist regarding the number of required visits (two or three) and measurements at each visit (two or three), and whether the first measurement is included in the diagnostic assessment (Table 1). These requirements pose challenges in practice, including increased healthcare costs and barriers to patient compliance [33], underscoring the need for practical and balanced approaches in clinical practice.
Blood Presure Measurement in Youth
Best practice principles for BP measurement in youth are relatively consistent across international guidelines and share similarities to those for adults. A key issue is the limited number of automated devices that have passed independent validation for accuracy in youth [34]. Currently, www.stridebp.org lists only 14 office/clinic devices and 3 devices each for home and ambulatory use. While current guidelines allow for initial screening with automated devices, confirmation of apparently high BP with the auscultatory method is recommended given that the first and fifth Korotkoff sounds were used to develop normative tables [17, 18, 27].
White coat hypertension (hypertensive office BP but normal out-of-office BP) affects 4–10% of youth in the community [35, 36], and 13–46% of children referred to specialist clinics for suspected hypertension [37,38,39]. Thus, ambulatory blood pressure monitoring (ABPM) is required to confirm a hypertension diagnosis, though its use is limited to children that are old enough to tolerate it. Although the AAP guidelines mention an approximate minimum age of 5 years, poor tolerability was reported in 32% of 14–16-year-olds, highlighting the need for technological development in pediatric ABPM [40]. The need of more comprehensive normative ABPM data—covering a broader geographical area and demographic range, and use of widely-used devices—is also recognized [41]. ABPM can also detect masked hypertension (normal office BP but hypertensive out-of-office BP), which occurs in 10.4% of youth and is associated with subclinical CV outcomes including left ventricular hypertrophy and higher pulse wave velocity (PWV) [42, 43].
While population-wide screening for masked hypertension may not be feasible, ABPM is recommended to identify masked hypertension and abnormal circadian BP variations in high-risk youth, including those with chronic kidney disease, diabetes, obesity, sleep-disordered breathing, or a history of aortic coarctation [41]. Particularly for those being treated for hypertension, there is evidence supporting the supplemental use of home BP monitoring alongside ABPM [44]. However, implementing home BP monitoring presents several obstacles, including the accuracy of unvalidated devices and practical challenges related to home measurement. Cultural factors, along with access and affordability issues, further complicate the adoption of both ABPM and home monitoring in some countries and settings [26].
Prevalence and Trends of Hypertension in Youth
An older systematic review and meta-analysis of 47 studies from 21 high-income and 26 low- and middle-income countries found the global prevalence of hypertension in those under 19 to be 4.00% [95% confidence interval (CI), 3.29, 4.78)], with higher prevalence in low- and middle-income countries [4.43% (3.16, 5.90)] compared to high-income countries [3.52% (2.74, 4.39)] [45]. Although this study used BP measurements obtained on at least three separate occasions, it used the Fourth Report instead of the AAP definitions, which may underestimate the prevalence. There has been a global rise in the prevalence of youth hypertension in recent decades: 1.26% (0.79, 1.84) in the 1990s, 3.30% (2.69, 3.97) in the 2000s, and 6.02% (4.38, 7.91) from 2010–14 [45]. However, trends vary by region.
In the US, after two-decades of decline, youth hypertension has plateaued or slightly increased according to AAP guidelines. Prevalence among children aged 8–12 years was 5.2% in 1999–2002, peaked at 6.2% in 2003–2006 and then decreased to 5.0% in 2007–10, with a slight further decline to 4.7% in 2011–14 and then stabilizing to 4.6% by 2015–18 [46]. Over the same period, adolescents aged 13–17 years had a steady decrease: 6.6% in 1999–2002, 5.5% in 2003–06, 4.6% in 2007–10, then bottomed out at 2.5% in 2011–14, before increasing to 3.7% in 2015–18 [46]. In China, youth aged 1–20 years had a consistent decline in hypertension prevalence (based on ≥ 95th percentile, though specific norms were not disclosed) from 18% in 2007 to 11% in 2010, and a further decline to 6% in 2014 [47]. In Korea, using the AAP guidelines, hypertension prevalence increased in youth aged 10–18 years from 5.4% in 2007–11 to 7.8% in 2012–16 and further to 9.9% in 2017–20 [48]. Similarly, in India, youth aged 1–18 years showed a rising trend in hypertension (defined as ≥ 95th percentile, with the BP norms not reported) before declining: 2% before 2000, 3% from 2001–05, 9% from 2006–10, 7% from 2011–15, and 6% from 2016–20 [49]. In Africa, data from meta-analysis suggests an upward trend with studies from 1996–2017 estimating a 5.5% prevalence of hypertension using the Fourth Report definition [50], while studies from 2017–20 estimate the prevalence at 7.5% according to the AAP guideline [51].
When evaluating prevalence estimates, it is important to recognize the deviation from guideline-recommended diagnosis of hypertension, which require consistently elevated BP across multiple measurements and clinic visits, and the single-visit measurements predominantly used in these prevalence studies. This practice likely leads to an overestimation of hypertension prevalence in youth. However, provided the definition of hypertension and the measurement methods are consistent, the observed trends should reflect true changes in prevalence.
Key Risk Factors for Pediatric Hypertenion
The global rise in pediatric hypertension is primarily attributed to the coinciding obesity epidemic among youth [33], but this trend is not universal. For example, China [52] has reported a decline in hypertension prevalence despite rising obesity, suggesting that multiple factors contribute to pediatric hypertension. According to the AAP guideline, these factors include older age (> 6 years) prenatal and maternal risk factors (maternal hypertension, low birth weight), lifestyle factors such as physical inactivity and poor nutrition (high salt intake, low fruit and vegetable consumption), and negative youth/prenatal experiences (maltreatment, anxiety) [17]. Other contributing factors are sleep disorders (sleep duration ≤ 8 h/night, poor sleep quality, sleep deprivation, obstructive sleep apnea) [53,54,55], sedentary behaviors (screen time > 2 h/day) [56], tobacco exposure (both active and passive smoking) [57], environmental factors (air pollution) [58], and social determinants (low family income) [46]. Additionally, sex and race differences play a role, with males and Blacks showing higher BP levels from the age of 12 years [59].
Familial aggregation or resemblance of BP shows that hypertension traits cluster within families due to genetic and shared environmental factors [60]. The HERITAGE Family Study reported maximal heritability (genetic and environmental) of 46% for SBP and 31% for DBP, with this higher among Blacks (SBP, 68%; DBP, 56%) than Whites (SBP, 43%; DBP, 24%) [61]. Approximately 50–60% of BP familial aggregation is genetic heritability [62], particularly in early-onset hypertension [63]. Together, familial aggregation studies outline the potential to identify hypertension and manage risk early in life.
Family history is a valuable predictive tool in pediatric settings, where children of hypertensive parents have higher and faster rising BP levels from infancy [64, 65]. Niiranen et al. [63] found that adults whose parents were diagnosed with hypertension at a younger age had higher risk of hypertension themselves. However, parental hypertension history does not account for the full genetic risk as it includes non-genetic heritability factors such as shared behaviors and environments. Adding parental hypertension history with youth BP and modifiable risk factors improves prediction of adult hypertension, but including genetic risk can further refine these predictions [66].
Genome-wide association studies identify genetic variants associated with elevated BP [67, 68] that can be compiled into a genetic risk score (GRS) or a more extensive polygenic risk score (PRS). While both scores predict genetic predisposition to hypertension, the PRS covers a broader range of genetic influences, and its use is becoming more widespread due to advances in computational and genomic technologies. In the Cardiovascular Risk in Young Finns Study, a GRS derived from 13 SNPs associated with life-course BP since childhood [β for 1-standard deviation (SD) increase in GRS: 0.47 mmHg for SBP; 0.53 mmHg for DBP, all P < 0.01, 95% CI not reported], even after adjusting for age, sex, and body mass index [69]. Similarly, pooled data from two studies found a GRS based on 29 SNPs associated with SBP at age 6 years [per-allele effect sizes, β (standard error) 0.097 (0.039) mmHg], but not with the changes between ages 6 to 17 years [70]. The genetic determinants of BP may evolve as individuals age [71], indicating variability in the genetic drivers of hypertension at different life stages. A recent initiative developed a youth-specific GRS for hypertension including 16 SNPs with the aim to enhance the genetic foundations of hypertension in youth and aid prediction [72]. However, translating these genetic insights into clinical practice faces significant challenges and requires further research to identify barriers and potential solutions.
Ultimately, hypertension in the young arises from a complex interplay of lifestyle, environmental, and genetic factors. The extent to which lifestyle modifications can mitigate the impact of genetic predispositions on BP across the life-course remains unclear. However, a study on adults suggests that lifestyle impacts on incident hypertension are consistent across different PRS groups [110].
Consequences of Youth Blood Pressure
Elevated BP in youth increases the risk of adult hypertension and is adversely associated with both immediate and long-term cardiovascular health outcomes. This includes vascular aging (characterized by structural and functional alterations in the vasculature) and cardiac damage, and overt CV disease in adulthood.
Youth Blood Pressure and Adulthood Blood Pressure
Substantial data published from cohort studies over the last 50 years show the tendency for BP to track (or persist) from youth to adulthood; summarized in meta-analyses by Chen et al. (50 studies, correlation coefficients of 0.38 for SBP and 0.28 for DBP) and Toschke et al. (29 studies, correlation coefficients of 0.37 for SBP and 0.31 for DBP) [5, 6]. Recently, an international study involving 38,589 participants found a correlation coefficient of 0.44 for SBP tracking from childhood to mid-adulthood over 35 years [9], while a meta-analysis showed that each 1-SD increase in youth SBP increases the odds of adulthood hypertension by 1.72 times (95% CI, 1.50, 1.95) [73]. A summary of key studies that assess the potential of raised BP in childhood to predict adult hypertension is provided in Table S1. However, these studies tend to have small sample sizes, lack, or do not consider, BP measurements in the intervening period, or use non-standardized definitions for high-risk BP categories. As such, the US Preventive Services Task Force (USPSTF) has called for future research to adopt standardized definitions [74], such as the AAP-defined high thresholds [75], to enhance understanding of hypertension transition from youth over the life-course.
Recent cohort data has also examined BP developmental trajectories, using multiple measurements that span youth through to adulthood. From puberty, males exhibit a steeper increase in SBP, peaking in young adulthood (age 26 years) at levels 8.2 mmHg (95% CI, 6.7, 9.8) higher than in females [76]. Females tend to catch up by their seventies, having more rapid increases in SBP later in life [76]. Data from the Bogalusa Heart Study supports these findings, showing distinct SBP and DBP trajectories by sex and race from 4 to 51 years [59]. This study also found higher BP levels and rates of increase throughout puberty and young adulthood associated with increased odds of hypertension in mid-adulthood [59]. Despite debate over the clinical application of these trajectory analyses [77], they, along with the tracking data, suggest the early origins of adult hypertension begin in youth, providing opportunities for early prevention.
Youth Blood Pressure and Target-Organ Damage
Cross-sectional studies (detailed in Table S2) have shown the association between youth BP and target-organ injury including vascular alterations such as increased carotid intima-media thickness (IMT) and arterial stiffness, cardiac changes indicated by higher left ventricular (LV) mass index (LVMI), and potential cognitive impairments. However, the association between youth BP and kidney injury, particularly microalbuminuria (urine-albumin-to-creatinine-ratio), remains unclear with current data not showing significant differences between normotensive and hypertensive adolescents [78], but there is a need for more sensitive markers to detect early kidney injury.
The long-term association of youth BP with markers of target-organ damage in adulthood (Table S3), focusing mainly on structural [IMT, coronary artery calcification (CAC)], mechanical [arterial stiffness, e.g., PWV, carotid distensibility (cD)], and functional [brachial flow-mediated dilatation (FMD)] markers of subclinical CV disease, and markers of cardiac damage (LVMI) [79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99] is well established. However, limited evidence exists for outcomes of cognitive function and kidney health [100,101,102]. An important systematic review and meta-analysis of 12 cohorts published in 2020 found that elevated BP in childhood accelerates vascular aging [high PWV (defined as ≥ age-, sex-, and heart rate-/study-specific 80th percentiles): OR (95% CI), 1.83 (1.39, 2.40); high carotid IMT (defined as ≥ age-, sex-, and study-specific 90th percentile): 1.60 (1.29, 2.00)], and increased the odds of developing LV hypertrophy (defined as LVMI > 49.2 g/m2.7 in males and LVMI > 46.7 g/m2.7 in females) [1.40 (1.20, 1.64)] in adulthood [7]. Moreover, findings from the i3C Consortium suggest youth SBP thresholds predictive of increased adult carotid IMT are lower than current definitions for elevated youth BP (90th percentile) by the AAP [88]. These insights call for reevaluation of existing definitions to better align with preventive efforts [103].
Life-Course Blood Pressure and Target-Organ Damage
Recognizing the role of youth BP on adulthood subclinical CV risk, research has begun to address risk development across the life-course from childhood to adulthood. Studies using BP data from two time-points have shown that individuals with persistently elevated BP in both youth and adulthood have the highest risk for adult markers of early vascular aging (carotid IMT [104] and PWV [105]). Conversely, those who resolve their elevated BP from childhood to adulthood largely do not show an increased risk, although a small residual risk remains. These results provide impetus for outlining modifiable factors associated with the resolution of raised BP [106] that could be targeted across the life-course.
However, analyses using BP from only two time-points in youth and adulthood could not fully assess the impact of the duration or timing of exposure [104, 105]. Research involving multiple BP measurements from youth to adulthood that consider cumulative BP (usually calculated as the area under the curve from serial measurements [89, 107,108,109,110] or from trajectories [111, 112]) suggests that prolonged exposure to high BP contributes to vascular aging and cardiac damage. A recent study outlined cumulative BP as the most important risk factor for markers of early vascular aging (PWV, IMT) compared with other factors such as lipids and body mass index [107]. While useful in describing long-term BP burden, these analyses do not determine specific life stages at which the BP-outcome association may vary—information that could optimize screening and prevention efforts.
In response, recent studies have employed advanced life-course modelling to determine the relative contributions of BP at different life-stages. These studies consistently find that while BP at each examined life-stage directly associates with the outcomes, the extent of the contribution varies depending on the outcome. For example, BP at different life-stages from infancy appears to provide an equal contribution to adult carotid IMT [113], whereas for PWV, BP levels measured closest to the outcome contribute most [114]. These findings suggest that while maintaining lower BP levels throughout life is ideal, controlling high BP at specific life-stages can still likely reduce CV risk.
Despite the value of these studies in understanding the long-term risks associated with BP, the complexity of the required data limits their practical application in clinical settings. An alternate, more feasible approach for clinicians might involve using the age at hypertension onset both in parents [63] and in the child to assess risk, with earlier onset related to higher risk of incident subclinical CV disease [115]. However, this research has primarily been conducted in adults, leaving a gap in our understanding of how knowledge of early versus later onset hypertension affects youth, noting our discussion above on tracking of BP from youth to adulthood.
Youth Blood Pressure and Clinical Cardiovascular Disease
While there is substantial evidence linking youth BP with subclinical CV risk, its association with clinical CV events is less well established. Early studies, like the Swedish 1969 male conscript cohort first indicated an association between young adult (aged 18–20 years) BP and incident coronary heart disease [116], and stroke [117]. However, these results contrasted with those from younger participants (aged 6–18 years at baseline) in the Princeton-Lipid Research Clinics Follow-Up Study where elevated youth BP (≥ 90th percentile using the Fourth Report) did not associate with incident CV disease 26 years later [118].
The link between youth BP and CV mortality in adulthood was initially highlighted in the Harvard Alumni Health Study among 855 males aged 19 years at baseline with a mean follow-up of 30 years [119]. These findings were confirmed in a subsequent study with a longer follow-up duration and lager sample size that accounted for the potential influence of adult BP [120]. Comparable conclusions were drawn from an Israeli cohort where youth (aged 16–19 years) hypertension (SBP/DBP ≥ 140/90 mmHg) was associated with stroke mortality [121]. Another study among Swedish male conscripts found that among young adults (mean age 18.4 years), DBP above 90 mmHg was positively associated with all-cause mortality over a median follow-up of 24 years whereas SBP demonstrated a U-shaped relationship with mortality risk, showing the lowest risk at a level of 130 mmHg [122]. This U-shaped curve might be explained by associations of low SBP with factors such as poor social, physical, and mental wellbeing, along with issues in brain perfusion and reflex abnormalities. The study also addressed concerns of reverse causation, where pre-existing illness might lead to both low BP and higher mortality. Such concerns are minimized by the young age and low prevalence of disease of the cohort at baseline, and the findings remaining consistent even after excluding data from the early years of follow-up. Another study failed to show the association of hypertension (using the cut-offs from the Fourth Report) in younger American Indian youth (aged 5–19 years) and all-cause mortality over a median follow-up of 23.9 years [123]. These varied findings underscore the complex relationship between youth BP and adult CV events, highlighting the need for further investigation. Important insights have been gained from recent studies.
The i3C Consortium found youth SBP associated with increased risk of both fatal [per 1-SD, HR (95% CI), 1.34 (1.19, 1.50)] and fatal/nonfatal [1.33 (1.24, 1.42)] CV events in adulthood [9]. This study also found that SBP levels in the 50th to 90th percentiles—considered normal by most current guidelines—associated with increased risk, which was consistent with earlier research on subclinical CV disease. Follow-up of almost 2 million Israeli military conscripts recently showed that those with hypertension in adolescence had approximately twice the risk of overall and ischemic stroke at a median age of 43 years compared to those without hypertension [10]. While these studies have typically defined hypertension among generally healthy individuals, a recent study identified youth with more severe or symptomatic hypertension using hospitalization and physician claims, including both primary and secondary causes. This study found that youth with hypertension had a 2.06-fold higher risk of major adverse cardiovascular events over a median follow-up of 12.9 years compared to those without hypertension (95% CI, 1.94–2.19) [124].
Recent evidence from the Coronary Artery Risk Development in Young Adults (CARDIA) Study found that 15-year cumulative SBP from young adulthood (aged 18–30 years), quantified as area under the curve, associated with increased risk for heart failure [per 1-SD increase: HR (95% CI), 2.14 (1.58, 2.90)], coronary heart disease [1.49 (1.19, 1.87)], and stroke [1.81 (1.38, 2.37)] [125]. Mendelian randomization analyses in the UK Biobank have further confirmed that genetically lower SBP across the life-course (2.9 mmHg lower on average) associated with 18% (95% CI, 0.79, 0.85) reduced odds of CV events [126]. Although this analysis did not specifically involve youth data.
Collectively, these studies outline the potential immediate and long-term CV benefits of early and effective BP management. This evidence needs to be considered with the generally lower awareness, diagnosis, and management of hypertension in younger populations compared to older adults, which might be further amplified in those with disadvantage [127]. The next section provides an overview of approaches for the prevention and treatment of elevated BP in youth.
Prevention and Treatment
Therapeutic Lifestyle Intervention
BP guidelines consistently highlight the fundamental role of lifestyle modification to prevent and treat abnormal BP in youth. [17, 18, 27] This is supported by several short-term randomized trials (refer to Supplement Text 1 for key trials) where lifestyle interventions aimed at lowering salt intake [128], promoting healthier diet choices [64] or regular physical activity and exercise [129] (especially high-intensity interval-based training [130]), and losing weight (reduction in body mass index standard deviation score) [131] have proven effective in lowering youth BP. Given the multifactorial nature of BP, the design of future lifestyle interventions should consider more detailed aspects of diet (microbiome [132]), mental health (symptoms of anxiety, depression and stress) [133], and the 24-h activity cycle (ideal time allocation) [134]. Furthermore, policies to control pollutants and environmental chemicals including outdoor (fine particles in ambient air) and indoor (household air pollution from inefficient household combustion) air pollution, environmental toxicants (heavy metals), noise pollution, and passive smoking, especially in low- and middle-income countries, seem pertinent [135].
Pharmacological Intervention
The decision to initiate pharmacological treatment for hypertension in youth depends on several factors (detailed in Table S4) [17, 18]. The safety and efficacy of antihypertensive medicine is less well-documented in youth compared to adults. A review by Gartlehner et al. which included six clinical trials with 909 participants aged 6 to 17 years, found that the risk of adverse events (such as dizziness and headache) was comparable between pharmacologic treatment and placebo over 2 to 4 weeks [74]. In terms of efficacy, a network meta-analysis involving 2,378 hypertensive children of median age of 12 years across 13 randomized placebo-controlled clinical trials (median follow-up of 35 days) found that angiotensin converting enzyme inhibitors and angiotensin receptor blockers, but not calcium channel blockers and thiazide diuretics, significantly reduced SBP and DBP compared to placebo [136]. Although these four drug classes are recommended as first-line treatments [17], individual responses vary [137], suggesting the need for personalized treatment plans. Data have emerged demonstrating that angiotensin converting enzyme inhibitors can lead to regression of LV hypertrophy (the process of reducing LVMI) [138], but similar evidence is lacking for other drugs, and there is no direct evidence linking LV hypertrophy reversal in youth with reduced CV risk later in life.
Overall, while clinical trials demonstrate short-term efficacy and safety of antihypertensive treatments in youth, evidence of their long-term efficacy and safety remains limited. This lack of long-term data contributes to the discordance and variability in guidelines and recommendation statements regarding BP screening and treatment in youth. The next section summarizes the various BP guidelines and recommendation statements for youth.
Screening in Youth: No Consensus
There is a lack of long-term randomized controlled trials that quantify the benefits and harms of BP screening and management in youth, particularly evidence demonstrating that early screening for abnormal BP can reduce the risk of future CV events. Reflecting this gap in evidence, the USPSTF in 2003 concluded that the evidence was insufficient to recommend for or against routine BP screening in youth [139]. Subsequent updates [140, 141] reaffirmed this stance, indicating an ongoing uncertainty in assessing the balance of benefits and harms of screening in children and adolescents. In contrast, guidelines from the AAP [17], the ESH [18], and the Hypertension Canada Guideline Committee [27] recommend BP screening in youth. Table 2 summarizes the recommendations for BP screening from these guidelines with the following section overviewing the evidence and challenges associated with BP screening in youth.
Potential Efficacy and Harms
High quality clinical trials for childhood BP screening and intervention to prevent adult events might never be possible and would be complex, expensive and require a large sample size. One of the arguments for screening is that we should not justify inaction (in the presence of so much other evidence) in the absence of potentially unobtainable evidence that some authorities require [142]. For example, cohort studies simulate efficacy by showing those able to resolve elevated youth BP have reduced odds of developing hypertension and markers of early vascular aging (carotid IMT [104] and PWV [105]) in adulthood, though data on CV endpoints is lacking. Additionally, findings from cross-sectional and longitudinal studies reinforce the potential benefits of early screening (Tables S2 and S3). Moreover, the primary physiological mechanism in pediatric hypertension is increased circulating volume, leading to elevated and sustained peripheral vascular resistance—a precursor to adult hypertension [143]. Measuring BP in pediatric physical examinations was advocated in the National Institutes of Health-sponsored expert panel report [144], and endorsed in the 2017 AAP guideline [17], emphasizing its importance in the early detection and management of hypertension. The implementation of BP measurements in routine school entry physical exams in some regions, such as in the US [145], exemplifies the feasibility of early hypertension screening.
The potential harms relate to high false-positive hypertension diagnosis in youth, including overdiagnosis and unnecessary treatment. Accurate BP evaluation is a basis of screening, yet guidelines lack consensus on measurement protocols (Table 2). Recent evidence underscores the need for consistency among pediatric guidelines in recommending repeat BP measurements for hypertension diagnosis, as there is considerable individual variation in SBP change among consecutive readings at each single visit that can influence BP classification [146]. ABPM improves the accuracy of BP evaluation by capturing day and night fluctuations [17], but multiple BP readings could increase the chances of diagnosing hypertension. Furthermore, the potential discomfort caused by ABPM during sleep can contribute to an overestimation of ambulatory hypertension, underscoring the importance of educating patients about the procedure. Additionally, ABPM-specific hypertension thresholds are understudied. The optimal balance between accurate evaluation versus feasibility and cost of screening, especially in low- and middle-income countries with limited resources, remains under examined. Weak predictive ability from youth BP to future CV risk is another concern (C statistics≈0.60–0.68 for adulthood hypertension, carotid IMT and PWV) [147], although screening protocols with adjunctive predictors such as familial predisposition, obesity, and genetic data might improve prediction [66].
Challenges in Hypertension Diagnosis
The first challenge relates to youth hypertension thresholds. The current threshold for youth hypertension set at the 95th percentile was criticized by the USPSTF as an “arbitrary statistical point” [144]. Using this hypertension threshold to predict adult CV risk results in high specificity but low sensitivity, suggesting some at-risk individuals remain undetected [118]. Recent evidence suggests employing a lower percentile (70th-80th percentile for SBP) for screening to increase sensitivity while minimizing reduction in specificity, improving early identification without significantly increasing false positives [147]. In support of revised hypertension definitions, mentioned above, evidence is consistently showing subclinical/clinical CV risk can begin at BP levels below the conventional 95th percentile threshold [9, 88]. Moreover, the proportion of adult elevated BP attributable to elevated child BP was estimated to only be about 10% [106], and youth with BP elevations within the normal range can still progress to adulthood hypertension [147], highlighting the benefits of early prevention. The AAP guidelines respond to these findings by recommending more inclusive cut-offs for initial screening [17]. Consensus is emerging that lowering youth BP thresholds is warranted [103, 148]. However, lowering thresholds will need to be weighed against the added burden—due to higher prevalence of hypertension—on the healthcare system this will create, and will vary by country/region.
The complexity inherent in pediatric BP classifications—owing to their reliance on a matrix of age-, sex-, and height-specific percentiles—poses another significant challenge for routine screening. The AAP guidelines provided simplified cut-offs for initial screening for children aged 1–12 years, based on the sex- and age-specific 90th BP percentile value at the 5th height percentile [17]. However, this approach showed low PPV of < 50% [149]. In contrast, data from the NHANES showed a simplified table using a higher height percentile (75th) had both high PPV (85.0%) and negative predictive values (NPV) (98.6%) in children aged < 13 years [150]. Additionally, the 95th BP percentile with 22 fixed cut-offs emerged as the most effective among 11 simplified options, offering the highest PPV (~ 90%) and a NPV of 100%, outperforming the more complex Fourth Report cut-offs [32]. However, the age restriction above six years and the lack of CV endpoints in these studies, and the potential impact of variation by population factors needs to be determined [149].
Cost-Effectiveness of Blood Pressure Screening
Cost-effectiveness of any screening program is a central consideration. A simulation study in the US population aged ≥ 18 years showed that population-based screening of BP is modestly cost-effective (USD 48,500/quality-adjusted life year) [151]. In another simulation study among US adolescents aged 15 years, neither population-based screening coupled with treatment for hypertension and LV hypertrophy, or targeted screening among adolescents with overweight/obesity, exhibited superior cost-effectiveness than population-level lifestyle modifications (salt reduction, increased physical activity) [152]. However, these studies did not consider younger age groups, other possible subgroups being targeted (e.g., with family history of hypertension), frequency of screening, cost of personnel, subsequent treatment costs, and likely lack of generalizability to other countries and health systems. The application of machine learning might assist in disentangling these uncertainties [153].
Blood Pressure Screening in Low- And Middle-Income Countries
Guidelines on youth BP screening have only been established in high-income countries. However, screening strategies in low- and middle-income countries require particular attention due to the challenges these regions face, including other essential health needs with limited healthcare resources, disparities in health literacy, and higher hypertension prevalence [135]. Adult studies in developing countries have shown community-based screening (at schools and community events) involving task-shifting to non-physicians and community-based health workers as an effective approach to screen and manage BP [154, 155]. Digital health technology (e.g., education program with text messages, using mobile devices and apps) is another promising strategy in locations where these devices are pervasive [156], as it allows for remote monitoring and can improve access to healthcare services in rural or hard-to-reach areas.
Conclusion
We positioned recent research on BP in children and adolescents within the broader field. We advocate for attention on the prevention and management of BP in youth, maintaining a cautiously optimistic standpoint. While we recognize primordial prevention as the ideal, early screening and subsequent interventions hold promise. We outline needs for ongoing research to continue to address the critical evidence gaps (Table 3) and advocate for a global perspective to formulate BP definitions and prevention strategies tailored to the unique contexts of low- and middle-income versus high-income countries.
Data Availability
No datasets were generated or analysed during the current study.
Abbreviations
- AAP:
-
American Academy of Pediatrics
- ABPM:
-
Ambulatory blood pressure monitoring
- BP:
-
Blood pressure
- CAC:
-
Coronary artery calcification
- CARDIA:
-
Coronary Artery Risk Development in Young Adults Study
- cD:
-
Carotid distensibility
- CI:
-
Confidence interval
- CV:
-
Cardiovascular
- DBP:
-
Diastolic blood pressure
- ESH:
-
European Society of Hypertension
- FMD:
-
Flow-mediated dilatation
- GRS:
-
Genetic risk score
- HR:
-
Hazard ratio
- i3C:
-
International Childhood Cardiovascular Cohort
- IMT:
-
Intima-media thickness
- LV:
-
Left ventricular
- LVMI:
-
Left ventricular mass index
- NPV:
-
Negative predicted value
- OR:
-
Odds ratio
- PDAY:
-
Pathobiological Determinants of Atherosclerosis in Youth
- PPV:
-
Positive predicted value
- PRS:
-
Polygenic risk score
- PWV:
-
Pulse wave velocity
- SBP:
-
Systolic blood pressure
- SD:
-
Standard deviation
- SNP:
-
Single-nucleotide-polymorphisms
- UK:
-
United Kingdom
- US:
-
United States
- USPSTF:
-
United States Preventive Services Task Force
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Meng, Y., Mynard, J.P., Smith, K.J. et al. Pediatric Blood Pressure and Cardiovascular Health in Adulthood. Curr Hypertens Rep (2024). https://doi.org/10.1007/s11906-024-01312-5
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DOI: https://doi.org/10.1007/s11906-024-01312-5