Identifying elevated blood pressure and hypertension in children and adolescents

A large body of evidence has shown that cardiovascular disease begins in early life,1-3 and multiple cardiovascular risk factors, including elevated blood pressure (BP), exacerbate the effects of age on the progression of cardiovascular disease from childhood to adulthood.4 Elevated BP in childhood tends to persist into adult life5 and is the single most significant risk factor for adult hypertension.6 It also contributes to damages in the cardiovascular system in childhood in the short term7 and to increased risk of cardiovascular disease in adult life in the long term.8, 9 As a result, the importance of identifying elevated BP and hypertension in children and adolescents has long been recognized. However, how to define elevated BP and hypertension in children and adolescents has been a challenge and remains controversial. Many professional organizations or research groups have developed various criteria for the identification of elevated BP and hypertension in children and adolescents.6, 10-15 The current standards used to define elevated BP in children are mostly determined by age-, sex-, and height-specific percentiles, without reference to adult cardiovascular outcomes because of limited investigations on the performance of the standards in predicting adult cardiovascular events. In this issue of the Journal, Fan and colleagues from the Beijing BP Cohort Study examined the performances of different standards in identifying childhood elevated BP and hypertension and in predicting adult hypertension and subclinical cardiovascular diseases.16 Left ventricular mass index, carotid-femoral pulse wave velocity, and carotid intima-media thickness were measured in a population-based, longitudinal cohort of 1177 participants who were examined for cardiovascular risk factors in childhood and the subclinical outcomes in young adult life.16 As expected, children identified as having elevated BP or hypertension according to any of the references, including the Fourth Report12 and its updated version,6 the international standards,11 and the Chinese standards,17 had increased risks of adult hypertension, increased arterial stiffness, and elevated left ventricular mass index. Using the four different standards, the authors also reported discrepancies in the prevalence of elevated BP in childhood and its associations with adult subclinical cardiovascular outcomes. According to the Chinese standards,17 18.7% of the participants in childhood were identified as having elevated BP or hypertension,16 which was significantly higher than identified by the Forth Report12 (14.2%) and its recent update6 (17.5%) and by the International Child Blood Pressure References Establishment Consortium11 (18.0%). Moreover, the Chinese standards performed equally compared with the updated US standards and better compared with the other standards in terms of the associations of elevated BP in childhood with adult subclinical cardiovascular diseases.16 Notably, sensitivity of the four references in identifying adult outcomes was low.16 Strengths of the study include a population-based, longitudinal cohort, a long follow-up time (23.5 years on average), and use of multiple subclinical outcomes in adults. Although the study used data from participants living in Beijing, China, a social-economically advanced region, the associations of childhood elevated BP with adult subclinical diseases are most likely to hold true across the country. However, similar studies using data from a nationally representative sample will improve generalizability. This study by Fan and colleagues16 feeds a growing need for examining the performance of different BP standards in predicting adult cardiovascular outcomes. Despite the latest efforts to assess the performance of various standards in identifying high-risk children based on adult subclinical cardiovascular disease,16, 18, 19 challenges and knowledge gaps still exist. First, more data that link childhood BP to adult cardiovascular disease events are needed. Such data would provide valuable and more definitive information for defining cutoff points for the identification of elevated BP and hypertension in children and adolescents because outcome-based definitions will be more appropriate than distribution-based, somewhat arbitrary definitions. Fortunately, these data are becoming increasingly available, for example, from the International Childhood Cardiovascular Cohort (i3C) Consortium,20 which includes five cohort studies from the United States, one from Finland, and one from Australia, all beginning in childhood. The i3C Consortium is collecting data on hard cardiovascular events (morbidity and mortality). In the short term, studies using subclinical outcomes, such as by Fan and colleagues,16, 19 to examine the performance of different standards for identifying elevated BP in children, particularly in those 6 years or younger, should be encouraged. In addition, assessing subtle changes in the cardiovascular system in children by noninvasive technologies should also be informative.21 Second, although harmonized, cross-population standards may facilitate comparisons of results across populations, such standards may, to different degrees, misclassify BP status in different populations.10, 15 It has been well documented that significant ethnic and geographic differences exist in BP levels, cardiovascular disease spectrum, and the association of childhood BP with adult cardiovascular risk.22-25 Consequently, population-specific standards may be more appropriate in identifying elevated BP or hypertension in children and adolescents. Population-specific standards should be developed if not yet available, used, and updated when new evidence becomes available. Of note, developing national references should be based on normal weight samples, as has been done for the development of the updated US standards6 Nationally representative samples should also be used. Developing national references should ideally be coordinated and done by an authoritative organization; otherwise, discrepancies and confusions may arise even for a single country.10, 17 Third, all of the current BP standards have been developed based on BP measurements at a single visit, mostly by the auscultatory method. Mercury sphygmomanometers are disappearing and being replaced by oscillometric or other new technology-based BP devices in clinical use.6 In addition, ambulatory BP monitoring provides critical information on mean BP, variability, and circadian patterns, which are all relevant to cardiovascular risk26 and is able to identify or confirm white-coat hypertension and masked hypertension.6 Ambulatory BP monitoring–based data will help refine BP standards in children and adolescents. Clinicians and healthcare professionals should be aware of the discrepancies in BP levels measured by different devices and their clinical implications. Fourth, according to current available standards, BP measurements from only one or just a few visits are used to determine BP status. Longitudinal BP patterns during childhood with growth and development taken into account are also very important. Evidence from the Bogalusa Heart Study shows that childhood BP trajectories are closely associated with risk of adult hypertension27 and left ventricular hypertrophy (T. Zhang, S. Li, L. Bazzano, J. He, P. K. Whelton, W. Chen, unpublished data), independently of absolute BP levels. Such information is mostly lacking in other countries/populations. Electronic health records and the increasing use of ambulatory BP monitoring will clearly help make it feasible and easier to collect longitudinal data for the purpose of identifying long-term patterns and linking these patterns to adult cardiovascular disease.6, 28 Fifth, the current available national or international standards are age, sex, and height specific, resulting in a large number of cutoff points, which are cumbersome in clinical practice. Simplified criteria have been proposed to ease such burdens.18, 19 However, these simplified criteria still have concerns, such as lack of data in younger children below age 6 and misclassifications; clinical utility of simplified criteria to guide clinical practice is yet to be established in further studies.6 As electronic healthcare systems are increasingly used, elevated BP in children can be marked with the age-, sex-, and height-specific percentiles integrated into the electronic systems. Finally, there may be a need to modify the current standards in children and adolescents because the cutoff points for adult normal BP have been changed to 120/80 mm Hg.29 The updated US guidelines for children 13 years or older used the same 120/80 mm Hg cutoffs to define normal BP.6 Given that BP increases with age even after age 13, it seems that using the same 120/80 mm Hg cutoff points to define normal BP in this young group may be questionable. New data to identify specific BP levels associated with adverse cardiovascular outcomes will inform the appropriateness of the 120/80 mm Hg criteria in this age group. Identifying elevated BP and hypertension in children and adolescents is challenging. The greater challenge is how to treat or intervene after a diagnosis has been made. Evidence from clinical trials, the gold standard to establish causality, to examine the efficacy of nonpharmacological and pharmacological interventions to prevent adult cardiovascular events in high-risk children is still lacking because of the fact that such clinical trials remain challenging, if not impossible, to perform.6 While findings by Fan and colleagues16 underscore the importance of addressing elevated BP and hypertension in childhood, childhood cardiovascular risk factors are not limited to elevated BP or hypertension. Although it is beyond the scope of this commentary, excessive body weight, dyslipidemia, and insulin resistance, along with psychosocial risk factors30, 31 in childhood also need to be addressed early.32, 33 Despite the challenges and uncertainties, however, consensus is that children, regardless of their cardiovascular risk profiles, should adopt a healthy lifestyle, including a healthy diet, routine moderate to rigorous physical activity, and avoidance of harmful behaviors such as smoking and drinking.34, 35 Further, for those who have been identified as having a heightened risk profile, not necessarily limited to elevated BP or hypertension, a more aggressive intervention strategy, sometimes involving pharmacological interventions, should be adopted. We would like to acknowledge funding support by grants R01AG016592 from the National Institute on Aging, R01HL121230 from the National Heart, Lung and Blood Institute, and P20GM109036 from the National Institute of General Medical Sciences. The authors have no conflicts of interest to declare.