BLOOD PRESSURE MONITORING AND MANAGEMENT (J REDON, SECTION EDITOR)

Ambulatory Blood Pressure Monitoring in Childrenand Adolescents: Coming of Age?

Empar Lurbe & María Isabel Torró & Julio Álvarez

Published online: 17 April 2013# Springer Science+Business Media New York 2013

Abstract Over the last years, ambulatory blood pressuremonitoring has been introduced into the pediatric popula-tion, contributing to a significant increase in the bulk ofknowledge of crucial clinically relevant issues. Guidelineshave established the currently known conditions where am-bulatory blood pressure monitoring is useful and where itwill provide additional information in children and adoles-cents. How common and important the intra-individual dif-ferences are within clinical and ambulatory blood pressure isthe keystone to the use of ambulatory blood pressure mon-itoring as a diagnostic tool. By using not only office, butalso ambulatory blood pressure, four possible situationsarise. Two of these have values in agreement fornormotension or hypertension. Two have values that arediscrepant. The latter two are known as white coat andmasked hypertension. The relationship with hypertension-induced organ damage, the prognostic value and the assess-ment of treatment goals are key issues of ambulatory bloodpressure monitoring. In children, the accurate identificationof hypertension at the earliest possible age would, therefore,give health-care providers the opportunity to initiate preven-tive measures, thereby reducing the chance of developingend-organ damage and its attendant morbidity and mortality.

Keywords Hypertension . Blood pressure . BP .

Ambulatory blood pressure monitoring . ABPM . Children .

Adolescents . White coat hypertension . Maskedhypertension . Organ damage

Introduction

Assessment of blood pressure (BP) is today accepted as aroutine in the health maintenance in children from threeyears old, despite the low prevalence of hypertension(HTN) in this age group. The reasons for this recommenda-tion are that BP values are one of the most importantmarkers of cardiovascular risk later in life [1], and therecognition of essential hypertension as the first cause ofhypertension late in the first decade and into the seconddecade of life. Likewise, the fact that BP tracks into adult-hood can help to detect early-on situations of cardiovascularrisk later in life [2]. An early identification of risk canprovide the opportunity for successful preventive actions.

Hypertension in children has some peculiarities that needto be considered. First is that the threshold to define HTNchanges throughout growth and maturation. Referencevalues were obtained from the percentile distribution ingeneral populations. The second derives from the preva-lence and causes of hypertension, which differ largely withage. While in the first years of life secondary hypertension isthe most frequent, in older children essential hypertension isthe first cause.

Casual BP measurement has provided the basis for presentknowledge of the potential risk associated with HTN [3], andhas guided patient management for many years. The intro-duction of ambulatory BP monitoring (ABPM) in pediatricshas given the opportunity to observe additional facts aboutBP behaviour with relevant clinical information [4].Experience accumulated in the last years has allowed forthe development of recommendations for the use of ABPM.The Fourth Report on the Diagnosis, Evaluation andTreatment in Children and Adolescents [5••], the AmericanHeart Association Atherosclerosis, Hypertension, andObesity in Youth Committee [6•] and the European Societyof Hypertension [7••], recommended the use of ABPM in theconditions delineated in Table 1.

E. Lurbe (*) :M. I. Torró : J. ÁlvarezDepartment of Pediatrics, Consorcio Hospital General, Universityof Valencia, Avda Tres Cruces 2,46014 Valencia, Spaine-mail: empar.lurbe@uv.es

E. Lurbe :M. I. Torró : J. ÁlvarezCIBER Fisiopatologia Obesidad y Nutricion (CB06/03), Institutode Salud Carlos III, Madrid, Spain

Curr Hypertens Rep (2013) 15:143–149DOI 10.1007/s11906-013-0350-7

Quality of Recordings

At the beginning of the use of ABPM in children and ado-lescents, feasibility and quality was a relevant issue since itwas applied to subjects with a large range of ages and bodysizes, and in which physical activity was difficult to control.Feasibility was tested performing 24-h monitoring in a widerange of ages, and it was found to be possible even in childrenfrom 3 years old. The quality was tested by our group inchildren and adolescents from 3 to 18 years old using anoscillometric device. In this group, 84 % of the 24-h ABPMattained a percentage of successful measurements greater than80 % [8], a percentage that was considered to be of a highquality. The factors related to the rate of successful measure-ments were age and BP values. The best recordings werethose performed in the oldest children and those with thehighest BP values. The reasons for this could be the betterfollow-up of instructions by the oldest children, and that largepulse wave oscillations decreased the potential for erroneousmeasurements [8]. However, both age and systolic BP ac-count for a small percentage of the successful readings.Acceptance to the device and compliance with the monitoringprocess play an important role in the quality of the recordings.

Characteristics and Reference Values

The BP values measured in ambulatory conditions using auto-matic devices reflect the values of regular living conditions andthe behaviour profile for a whole day. The average of ambula-tory BP values correlates positively to office BP counterparts[9]. Usually, ambulatory BP in normotensive children is higher

than office, while in hypertensives, the relationship is reversed[10]. The reason is not well understood, although the degree ofactivity during living conditions and the overestimation of BPvalues with oscillometric monitors, in the range of low BPvalues, may provide the explanation [11].

Office BP in children and adolescents increases duringage and maturation. The increment rate of ambulatory BP,however, is lower than the office BP across age and height.While an increment exists for systolic BP, no changes areobserved in diastolic BP [9]. During adolescence, changesin BP are more evident, since it is a period with fast growthand hormonal changes. In boys, systolic BP increases from10 to 16 years of age, while in girls systolic BP stabilises, oreven decreases after 13 years [12].

Circadian BP profile is also observed in this age group,with higher values during the daytime period than thoseduring nighttime as a consequence of activity in the awak-ening hours. In our experience, in a study carried out inchildren and adolescents with a wide age range, 83 % of thechildren have a significant systolic diurnal BP rhythm and89 % for diastolic BP [13]. The nocturnal BP fall, calculatedas the difference between the daytime and nighttime period,is normally distributed. Nocturnal BP fall and circadian BPprofile have a low reproducibility [14], since they depend ondegree of physical or mental activity and the number ofsleeping hours [15]. Assessment of circadian variability inchildren and adolescents is important in certain pathologicalconditions, even in the absence of HTN [16]. Consideringthe low reproducibility of BP circadian variability, one 24-hour recording is probably insufficient to fully characterise adiurnal BP profile.

According to the criteria of the Fourth Report on theDiagnosis, Evaluation, and Treatment of High BloodPressure in Children and Adolescents [5••], shared by theGuidelines from the European Society of Hypertension[7••], normotension in children is defined as systolic anddiastolic BP below the 90th percentile for age, gender, andheight. Hypertension is defined as systolic and/or diastolicBP persistently at or above the 95th percentile, measured onat least three separate occasions with the auscultatory meth-od. Those children with systolic or diastolic BP at or abovethe 90th percentile but below the 95th percentile are classi-fied as having high-normal BP. Likewise, adolescents withBP at or above 120/80 mmHg, even if below the 90thpercentile, are considered as high-normal BP. Althoughoffice BP is still the reference for the diagnosis of hyperten-sion, ambulatory BP may help to us to define BP categories.Therefore, the availability of reference values of “normalcy”is a key issue. Preliminary ones for ambulatory systolic anddiastolic BP have been obtained from some Europeanpopulations [17•]. The reference tables available until nowhave the limitation that they were constructed using a smallnumber of children for each strata of sex, age or height.

Table 1 Recommendations for 24-hour ambulatory BP monitoring.Reprinted from Lurbe et al. [7••]. Management of high blood pressurein children and adolescents: Recommendations of the European Societyof Hypertension. J Hypertens. 2009; 27:1719–1742, with permission

During the process of diagnosis

Confirm hypertension before starting antihypertensive drug treatment

Type 1 diabetes

Chronic kidney disease

Renal, liver or heart transplant

During antihypertensive drug treatment

Evaluation of refractory hypertension

Assessment of BP control in children with organ damage

Symptoms of hypotension

Clinical trials

Other clinical conditions

Autonomic dysfunction

Suspicion of catecholamine-secreting tumours

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Today, these tables will be a starting point to progress in thisimportant issue, to construct robust reference values.

The Role in Diagnosis

Using both office and ambulatory BP, four possible situationsarise. In two situations, when both office and ambulatory BPare in agreement, normotension or hypertension is confirmed.When the values are discrepant we are facing what is calledwhite coat or masked HTN. White-coat HTN is the elevationof a patient’s BP in response to the observer measuring the BP[18, 19]. It has been defined as a normal daytime ambulatoryBP, but with elevated office BP. The opposite phenomenon,masked HTN, consists of elevated daytime or awake ambula-tory BP with normal office BP [20, 21]. The discrepancybetween office and ambulatory BP has clinical relevance andis one of the fundamentals for the use of ABPM.

Prevalence and significance of these two discrepant condi-tions, white-coat and masked, are not well defined since theydiffer depending on the subjects analyzed. The main studies inthe prevalence and significance of white-coat and maskedHTN in children and adolescents are shown in Table 2.

White-Coat Hypertension

The prevalence differs largely among the studies published,with values ranging from very low to as high as 44 % [19].This is due to the fact that it depends not only on thethreshold selected to define HTN for ambulatory BP values,but also on the population included and the procedure usedfor the office BP measurements.

The thresholds selected for the upper limit of normal valuesof ambulatory BP are partly to blame for the elevated figures of

the white-coat phenomenon. The higher the ambulatory BPthreshold, the greater the white-coat phenomenon is [21].Sometimes the thresholds used are the same for both ambula-tory as well as for office BP. If not, they have been selectedcomparing age-and height-based reference values for office BPwith height or age based values for ambulatory BP [17•]. Thecharacteristics of the population included also contribute to thedifferences in prevalence. In two studies by Sorof et al. [19]and Stabouli et al. [22], which included children referred to aHTN clinic, white-coat HTN was reported in 44 and 12.9 % ofthe subjects, respectively. Other studies also performed inreferred subjects had figures similar to the previously men-tioned [23–27]. On the other hand, in one studywhich includedhealthy children and adolescents, white-coat HTN was diag-nosed in only 1 % [20]. This very low prevalence was due toboth the type of population studied and the method used toassess the office BP values. Office BP status was qualifiedusing the average of three measurements assessed by nurses,which reduced the potential for alarm reaction.

Concerning the significance of white coat HTN, childrenwith this condition tend to have a higher left ventricularmass index (LVMI) than confirmed normotensives, al-though no significant differences have been observed be-tween the groups [19, 22, 24]. Up to now, no long-termfollow-up data of children with white coat HTN at initialassessment is available in order to know the reproducibilityof the phenomenon, and to assess the impact of this condi-tion. If white-coat is an innocuous phenomenon or a preludeto future permanent adult HTN, needs to be assessed.

Masked Hypertension

The opposite phenomenon is the so-called masked HTN. Instudies that have explored this condition, it occurred in

Table 2 Association of ambulatory blood pressure with hypertension-induced organ damage of white-coat and masked hypertension inchildren and adolescents

Author Population Characteristics Prevalence White-Coat Prevalence Masked Association TOD

Sorof 2001 [19] 71 referred subjects 31 % – –

Matsuoka 2002 [22] 202 normo- hypertension 47 % – –

Matsuoka 2004 [24] 138 normo- hypertension – 11 % –

Lurbe 2005 [20] 592 population study 1.7 % 7.6 % LVH in masked

Stabouli 2005 [21] 85 referred subjects 12.9 % 9.4 % LVH in masked

McNiece 2007 [23] 163 referred subjects Stage 1 – 34 % 20 % LVH in maskedStage 2 – 15 %

Kavey 2007 [24] 119 referred subjects 52 % – LVH in white-coat

Lande 2008 [25] 217 referred subjects 31 % – –

Stergiou 2008 [26] 102 referred subjects 18 % 11 % –

Mitsnefes 2010 [27] 366 CKD subjects – 38 % LVH in confirmed and masked HTN.

Di Salvo 2011 [28] 76 aortic coarctation repair – 47.4 % LVH in masked HTN.

TOD target organ damage, LVH left ventricular hypertrophy, HTN hypertension, CKD chronic kidney disease

Curr Hypertens Rep (2013) 15:143–149 145

approximately 10 % of children and adolescents [20, 22,27–30], although a higher prevalence of 22 % has also beenreported [24]. Key issues, such as the persistence and thesignificance of the phenomenon, were analyzed in a prospec-tive study from our group [20]. Follow-up of 234 adolescentsdemonstrated that the abnormal elevation of the daytimeambulatory BP persisted in nearly 40 %. Adolescents withpersistent masked HTN were more than twice as likely tohave a parental history of HTN. Subjects with masked HTNwere also found to have a higher ambulatory pulse rate, bodymass index and more frequently left ventricular hypertrophythan normotensive subjects. Alone or in combination, thesecharacteristics predispose subjects to develop HTN and toincrease cardiovascular risk later life [20].

Because both HTN and LVH are the forerunners inadverse cardiovascular outcome [31, 32], when maskedHTN persists in childhood, it should be regarded as acondition that requires further follow-up and intervention.From a therapeutic approach, masked HTN in pediatricpatients is an indicator for further follow-up and the intro-duction of life style measures that promote cardiovascularhealth and have the potential to decrease BP or delay thedevelopment of HTN. Indeed, ambulatory BP is superior tooffice BP and highlights the complementary use of ABPMto conventional office BP measurement.

Pediatricians are faced with the serious problem of identi-fying subjects with the masked HTN condition, since all ofthem are normotensive in the clinical setting. It raises a veryimportant question: in which children should ABPM beperformed? While the question is yet to be answered,ABPM is useful not only for the stratification of risk inindividual subjects but also for increasing knowledge aboutthe BP behaviour and its clinical implication. Clearly, it is notpractical to perform ABPM in all subjects with normotensionin the office in order to unmask those with ambulatory HTN,but we must accept that children with masked HTN may be ata serious disadvantage if ABPM is not performed. Then,children with the highest risk to be hypertensive later in life,mainly parental history of hypertension, should be monitored.Once masked HTN is identified, repeated office BP measure-ments should be encouraged to detect the potential progres-sive rise in BP values.

Ambulatory Blood Pressure and Organ Damage

The use of ABPM has provided insights into the role of BPcomponents in the development of HTN-induced organdamage. The relationship between HTN, defined by officeBP values, and specific hypertensive target-organ damagehas not been well correlated. Ambulatory BP monitoring hasthe ability to obtain more accurate and reproducible BPvalues [9] and the estimation of circadian variability [13].

Therefore, ABPM has become a recognized tool in evalua-tion and prognosis [4], overcoming the limitations of casualBP measurements.

Numerous clinical studies in children, both with and with-out established renal insufficiency, have provided evidence onthe importance of ambulatory BP values in the progression ofrenal disease. The reduction in GFR and the increment inurinary albumin excretion (UAE) are markers of HTN-induced renal damage. Elevated BP values may contribute toincrease UAE, a marker of glomerular damage in primary andsecondary glomerulopathies. Cross-sectional studies havedemonstrated an association between a subtle increase inUAE and a clustering of cardiovascular risk factors and organdamage. However, in pediatrics, information on the validity ofmicroalbuminuria assessment is limited to diabetic subjects.

In patients with renal disease, regular use of ABPMfrequently uncovers abnormalities in circadian variabilityand allows for better BP control. A characteristic of renalfailure is the blunted nocturnal BP fall, the so-called non-dipper pattern [21]. The role of the pattern has been stressedin many studies as either a marker or a pathogenic factor ofkidney damage [33]. Patients with a decrease in glomerularfiltration rate (GFR) are likely to show less nocturnal dip inBP, and frequently show an increase in nocturnal versusdaytime BP levels, when these are compared with the BPprofiles from normotensives or hypertensives with a normalGFR [34, 35]. The prevalence of non-dipping pattern in-creases as renal function worsens. When GFR drops toextremely low levels of <1 0 ml/min, and creatinine reachesvalues greater than 600 μmol/l, more than 70 % of these endstage renal disease subjects had non-dipper pattern, a per-centage similar to that observed in dialysis patients. In bothadults and children after renal transplantation, an abnormaldecline in nighttime BP occurs almost universally [36–39].In children after renal transplantation 72 % of the subjectsshowed a reduced decline in nocturnal systolic BP, with24 % having greater nighttime than daytime BP [37].

Even when glomerular filtration rate is in the normalrange, abnormal circadian variability has been observed inseveral nephropathies, autosomic dominant polycystic kid-ney disease [40], reflux nephropathy [41, 42] and Type 1diabetes [16]. The greater bulk of information comes fromstudies in Type 1 diabetes. Throughout the diabetic ne-phropathy stages, 58 % of microalbuminuric and 80 % ofproteinuric subjects had a non-dipping pattern [43].

The abnormal increase in left ventricular mass (LVM)and/or geometry may be the most relevant HTN-induced earlyorgan damage. However, in children and adolescents, it ismore difficult to establish the relationship between HTN andleft ventricular hypertrophy (LVH) because growth and mat-uration introduce confounder factors. In fact, cross-sectionalstudies demonstrated that the main determinants of left ven-tricular growth are body size and sex, and to a lesser extent,

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BP [44, 45]. This was also supported from data from theBogalusa Heart Study, which showed that somatic growthand lean body mass, more than fat mass, contribute to cardiacgrowth [46]. In a longitudinal study, LVM tracks from early tolate adolescence to about the same degree as other importantrisk factors, such as BP and cholesterol [47]. In relation to thepotential role of adiposity in the increment of LVM, an asso-ciation has been observed in childhood, which tracks andbecomes stronger in young adulthood. Moreover, the increasein LVM from the child to the young adult is related to thedegree of increase in body mass index [48]. At the time toassess the “excessive LVM”, LVH operational thresholds havebeen established and recommendations exist for both thedefinition of excessive mass (>51 g/m2) and percentile distri-bution of mass and geometry. By using the excessive masscriteria, the prevalence of LVH ranges from 24 to 40 % inhypertensive children [49–52].

The relationship between LVM index (LVMI) and ambu-latory systolic BP is stronger than that observed with officesystolic BP [52–55], indicating that hemodynamic loadseems to play an important role in the growth of LVM thanpreviously recognized. Both sustained and masked hyper-tensive subjects had significantly higher LVMI than normo-tensives in cross-sectional studies [20, 22, 24].

Arterial structure and function have suffered the impact ofBP elevation from the beginning, but little attention was paidto vascular damage in the past. The introduction of non-invasive methods to assess vascular dysfunction and damagehas boosted knowledge in the issue. The most common pa-rameter to assess vascular structure is intima-media thicknessmeasurement in the carotid artery. Considering the influenceof growth and maturation, the values should be related topercentiles or expressed as standard deviation scores [56].

The information about the relationship between carotidwall-thickness and ambulatory BP is scarce and mainlyperformed in obese children. While one study providedstrong evidence that carotid intima-media thickness is in-creased in childhood primary HTN, independent of theeffect of obesity [57], recent findings have demonstratedthat obese children and adolescents have greater carotidintima media thickness than non-obese subjects independentof BP [58]. This suggests a possible role of childhoodobesity in the early onset of carotid artery atherosclerosis.

Prognostic Value and Goals of Treatment

The prognostic and clinical value of repeating ABPM over-time has been demonstrated for the first time in children andadolescents. Evidence has come from one study performedin normotensive type 1 diabetics, where nocturnal systolicBP was related to the development of microalbuminuria[59••]. An increase in BP during sleep preceded the

development of persistent microalbuminuria, and the pro-gression to microalbuminuria was less frequent when BPdecreased normally during sleep.

The second is the ESCAPE trial, which demonstrated theutility of ABPM in establishing the ambulatory BP goals toprotect the kidney in children and adolescents with chronickidney disease. The study was conducted in patients withdifferent glomerular and interstitial nephropathies. Thelong-term renoprotective effect of intensified BP control(with a target 24-hour mean arterial BP below the 50thpercentile) or conventional BP control (in the 50–95th per-centile) was assessed. Intensified BP control with target 24-hour BP levels in the low range of normal, below the 50thpercentile, confers a substantial benefit in reducing the riskto develop end stage renal disease among children withchronic kidney disease [60••].

Conclusions

In conclusion, ambulatory BP measurement is now an in-dispensable tool in the diagnosis and management of HTN.Detection of subtle BP abnormalities, early identification ofHTN, and whole-day control of HTN, are all facilitated byambulatory BP measurement. It is important to highlightthese abnormalities in the prevention of HTN and the sub-sequent cardiovascular and renal risk, especially in a popu-lation where intervention leads to greater benefits for theindividual and for the community as a whole. Enhancing theuse of ABPM for the management of HTN and for clinicalresearch should be mandatory for the paediatric age.

Conflict of Interest Empar Lurbe declares that she has no conflict ofinterest.

María Isabel Torró declares that she has no conflict of interest.Julio Álvarez declares that he has no conflict of interest.

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