Paediatrics & Child Health, 2018, 1–7

doi: 10.1093/pch/pxx207
Original Article

Original Article

Blood pressure in children with attention deficit/hyperactivity

disorder
Silviu Grisaru MD1, Melissa Yue BHSc2, Susan M. Samuel MD1, Kathleen H. Chaput PhD3,
Lorraine A. Hamiwka MD1
1
Department of Pediatrics, Cumming Section of Medicine, University of Calgary, Calgary, Alberta; 2Werklund School of
Education, University of Calgary, Calgary, Alberta; 3Departments of Pediatrics and Community Health Sciences, University
of Calgary, Calgary, Alberta
Correspondence: Silviu Grisaru, Alberta Children’s Hospital and Research Institute, University of Calgary, 2888 Shaganappi Trail,
Calgary, Alberta T3B 6A8. Telephone 403-955-7759, Fax 403-955-2203, E-mail [email protected]

Abstract
Objectives: Children with attention deficit/hyperactivity disorder (ADHD) are frequently treated
with psycho-stimulant agents causing a modest but significant increase in blood pressure and heart
rate. The objective of this study was to define blood pressure characteristics in children with ADHD
treated with a variety of medications in a community setup.
Methods: Children registered at a large paediatric clinic in Calgary, AB with documented histories of
ADHD were randomly contacted. Consenting participants had standardized office BP measurements,
ambulatory blood pressure monitoring (ABPM) studies and were asked to complete the sleep distur-
bance scale for children (SDSC) questionnaire. Findings were compared with data from the Canadian
Health Measures Survey (CMHS).
Results: Fifty-five children (47 males) aged 7 to 17 years (average 11.6 ± 2.5 years) with an average
BMI z-score of −0.37 ± 1.22 completed the study. All children were medicated, the majority (82%),
with various types of stimulant agents. Elevated office BP values were more prevalent than in the
CMHS; >90th percentile in 5 (9.1%) and >95th percentile in 3 (5.5%). ABPM confirmed ‘white coat
hypertension’ in 3 (5.5%), masked hypertension in 2 (3.6%) and nondipping in 28 (51%). The SDSC
score suggested that 43 (78%) children had disturbed sleep. Logistic regression modelling indicated
that nondipping correlated with disturbed sleep.
Conclusion: The ‘white coat’ phenomenon may be responsible for increased prevalence of elevated
rest/office BP values in children with ADHD. Prevalent sleep ‘non-dipping’ in this population is asso-
ciated with sleep disturbances but clinical significance of this finding requires further investigation.

Keywords: Blood pressure; Hypertension; Children; ADHD; ABPM.

BACKGROUND most frequently with a member of the psycho-stimulant med-

ications family (3). The incidence of ADHD and use of medi-
Attention deficit/hyperactivity disorder (ADHD) is a com-
cations for treatment, particularly psycho-stimulant agents, has
mon neurobehavioural childhood disorder that can continue
steadily increased over the last few decades (4,5). Efficacy of
into adulthood (1,2). A national population-based sample of
stimulant medications in alleviating symptoms of ADHD has
US children found that 8.7% of children aged 8 to 15 years, an
been well established since 1970s and over the last 40 years,
estimated 2.4 million, meet DSM-IV criteria for ADHD (1).
many different drugs belonging to this group have been devel-
Management of this disorder is based on pharmacotherapy,
oped, the latest addition being long-acting preparations (3).

©The Author(s) 2018. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. 1
For permissions, please e-mail: [email protected]

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Despite their proven efficacy, stimulant medications have (19). The ABPM was performed with the Welch Allyn ABPM
always been under intense scrutiny for potentially serious side 6100 monitor, with set parameters according to reference val-
effects such as insomnia, growth retardation, exacerbation ues provided by Wuhl et al. (20). The ABPM blood pressure
of pre-existing psychiatric disorders, adverse cardiovascular index was calculated by dividing the average blood pressure for
effects and abusive use (6). Concerns regarding an associated each patient by the 95th percentile blood pressure value specific
increased risk for sudden death have not been substantiated for that patient, such that an index greater than 1.0 is equivalent
by large observational studies (7). A modest but significant with an average BP greater than the 95th percentile (21). The
increase in blood pressure and heart rate are well known adverse operative protocol for ABPM administration and interpretation
effect of stimulants that have been documented in many retro- of results were conducted according to Urbina et al. updated
spective and prospective studies focusing on safety of specific by Flynn et al. (22,23). BMI and BMI z-score were calculated
agents (8–18). Nevertheless, population-based prospective based on height and weight recorded at the time of ABPM ini-
studies investigating the overall effect of drug therapy on blood tiation. Classification of BMI was made according to the CDC
pressure in children with ADHD are rare. The objective of this method (http://www.cdc.gov/obesity/childhood/).
study was to define blood pressure characteristics in a sample of Given the risk for insomnia associated with stimulant treat-
otherwise healthy children treated with a variety of medications ment and the possible effect of insomnia on nocturnal blood
indicated for ADHD and to compare prevalence of suspected pressure values, the sleep disturbance scale for children (SDSC)
hypertension in this cohort with the prevalence documented in questionnaire was also administered and filled out by parents
the general Canadian paediatric population. during the visit. The SDSC is a 26-item instrument for evalu-
ating sleep among children aged 3 to 18 years. It is validated at
a cut-off score of 39 to predict sleep disturbances in children,
METHODS with 0.89 sensitivity and 0.74 specificity (24). Higher SDSC
We conducted an observational comparative study, with pro- scores indicate increasing severity, with a cut-off score of 50 or
spective measurement of BP in a sample of children with higher marking ‘severe’ sleep disturbance.
ADHD, currently undergoing pharmaceutical treatment, at To compare prevalence of suspected hypertension in chil-
a large community general paediatric clinic in Calgary, AB. dren with ADHD with prevalence in the general paedi-
Following an official request for collaboration, three consent- atric Canadian population, we used office blood pressure
ing independent paediatricians practicing at the clinic, pro- values documented in our sample and available data from the
vided lists of all patients under their care with a documented Canadian Health Measures Survey (CHMS). The CHMS is a
diagnosis of ADHD. Patient names and contact information national, representative, cross-sectional, direct-measures sur-
were compiled in a single list in random order generated by vey of more than 15,000 Canadians aged 6 to 79 years who
a computer algorithm. Candidates were contacted by phone underwent anthropometric as well as blood pressure and
in the order they appeared on the randomly-compiled list for heart rate measurements during single visits to mobile exam-
preliminary consent as well as screening for eligibility to par- inations centres across Canada. In the CHMS, BP was also
ticipate. Children aged 5 to 18 years with a documented diag- measured with a calibrated oscilometric electronic device;
nosis of ADHD and receiving ongoing treatment with any type however there were six measurements 1 minute apart with
of medication indicated for ADHD were eligible for inclusion. the average of the last five being documented. Data from two
Interested subjects were scheduled for a clinic appointment cycles (2007 to 2009 and 2012 to 2013) were used for com-
during which a full medical history, physical examination and parison (25,26).
anthropometric measurements were performed, followed by Descriptive statistics included calculation of means and
initiation of a 24-hour ambulatory blood pressure monitoring proportions. Chi-square analysis was used to compare prev-
(ABPM) test. alence of blood pressure values in the prehypertension or
Children with pre-existing medical histories or physical hypertension range among children medicated for ADHD,
exam findings suggestive of other chronic diseases (particularly with children from the CHMS survey representing the general
chronic kidney disease, heart disease or diabetes mellitus) or Canadian paediatric population. Children were also grouped
taking any other prescribed medications were excluded from according to the presence or absence of ABPM abnormalities
the analysis. (mean ambulatory pressure > 95th percentile and/or sleep
Office blood pressure was measured with the Carescape nondipping) and were categorized as having sleep distur-
V100 (GE Healthcare) monitor three times, 2–5 minutes apart; bance, based on the SDSC score. A reverse stepwise-elimina-
an average of the last two measurement was recorded. Office tion logistic regression modelling process was used to assess
blood pressure values percentiles were calculated and classified the association between ABPM abnormalities and sleep dis-
according to the fourth report on the diagnosis, evaluation and turbance in the ADHD population, controlling for confound-
treatment of high blood pressure in children and adolescents ers as appropriate.

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RESULTS blood pressure above the 95th percentile was observed in

3.64% of cases, and sleep blood pressure load greater than 25%
The compiled randomized list of potential participants included
was observed in 18.8% of children in the study. Forty-three par-
240 children with a recorded diagnosis of ADHD. Contact was
ticipants (78%) scored more than 39 on the SDSC instrument
attempted with 145 families, 19 of whom were not reached due
to outdated/incorrect phone numbers. Of those reached, 26
were excluded since they were not taking any prescription med-
ications. Two patients declined participation and three were
excluded because of ongoing treatment for comorbid chronic
diseases. Of the remaining 95 eligible candidates, 57 were able
to coordinate an appointment and an ABPM test during the
study period. Two children were excluded from the final analysis
due to noncompliance with the ABPM test, leaving a sample of
55 participants. The study was terminated before all candidates
were contacted due to exhaustions of available resources. More
than 85% of children in the study sample were treated with a
type of psychostimulant medication indicated for ADHD: 36%
methamphetamine, 22% combination of dextroamphetamine
and amphetamine, 22% lisdexamphetamine and 3% dextroam-
phetamine. The rest of the children (14%) were treated with the
norepinephrine reuptake inhibitor, atomoxetine.
Descriptive statistics of participants’ demographics, BMI,
proportion of children with abnormal office BP as well as
available parallel data from the CMHS are shown in Table 1.
Office BP percentiles of the subjects are graphically illustrated
in Figure 1 and the distribution of ABPM parameters is shown
in Figure 2. We observed a significantly higher prevalence
of suspected prehypertension (P=0.031) and hypertension
(P=0.033) in the study sample, compared to the Canadian
paediatric population (Table 1). Blood pressure classification
combining results of office BP values and ABPM tests as well
as prevalence of sleep disturbances are listed in Table 2. The
ABPM studies demonstrated that all subjects with abnormal
office blood pressure values had ‘white coat’ hypertension or
could not be classified. Interestingly, the ABPM studies indi-
cated that more than half of the children in our ADHD sample Figure 1. Calculated office blood pressure (BP) percentiles of children
(51%, n=28) experienced nondipping. Sleep, mean ambulatory with ADHD. (A) Systolic BP percentiles; (B) Diastolic BP percentiles.

Table 1. Demographic characteristics and office BP of children with ADHD and children from the Canadian Health Measures Survey
(CMHS)
ADHD sample CHMS 2007–2009 CMHS 2012–2013
N (Boys %) 55(85.5%) 1850 (51.2%) 1899 (50.1%)
Age range, years 7–17 6–17 6–19
Average BMI/BMI-z score 17.9*/−0.37 19.6*/0.49 20.3/n/a
Overweight and obese, % 7.3%** 26.5%** 25.6%
Prehypertension (single office visit) 9.1%† 2.2% 3%†
Hypertension (single office visit) 5.45%‡ 0.8% 2%‡

Difference in proportions/means: *1.4 (95% CI: 15.3–16.9), P= 0.0004; **−0.192 (95% CI: −0.310–0.074), P=0.002; †0.043 (95% CI: 0.004–
0.141), P=0.031; ‡0.035 (95% CI: −0.005–0.114), P=0.033.
ADHD Attention deficit/hyperactivity disorder; BP Blood pressure.

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office blood pressure values compared to children in the general

population. However, ABPM in these children demonstrated
that this largely represents ‘white coat’ hypertension. Moreover,
office BP values suggesting prehypertension were not con-
firmed as such, using the BP classification criteria combining
office BP values with ABPM results. Systematic screening of
participants with ABPM identified potentially clinically signifi-
cant BP abnormalities that are not detectable by office BP mea-
surements, such as the high prevalence of nondipping, which
appeared to be well correlated with sleep disturbances. A high
prevalence of nocturnal BP load was also detected by ABPM as
well as two cases on masked hypertension.
This study was inspired by a previous retrospective obser-
vation, that in our centre, a significant proportion of children
referred for investigation of suspected hypertension had a
comorbid diagnosis of ADHD (27). The results of the current
study offer a partial explanation for this observation. Access
to the CMHS data provided a unique opportunity to compare
this sample of children medicated for ADHD with an appro-
priate control group of healthy Canadian children who were
also randomly recruited for anthropometric and BP measure-
ments using comparable equipment and methodology, except
for the total number of measurements (25,28). Prevalence
of elevated BP values in children sampled by the CMHS was
significantly lower than reported by many large retrospective
studies, some of which found the prevalence of elevated blood
pressure in children, on a single visit, to be as high as 15%
and even higher among obese children (29–31). However,
similar to most other studies, the CMHS also found over-
Figure 2. Ambulatory blood pressure (BP) monitoring results distribution weight to be a strong risk factor for both prehypertension and
among children with ADHD. (A) Ambulatory BP index; (B) Ambulatory hypertension. Interestingly, the higher prevalence of elevated
BP load. office BP values in children with ADHD does not appear to
be related to overweight as the average BMI of this group was
indicating a high prevalence of sleep disturbances, with more significantly lower compared to the CMHS sample of healthy
than half (51%) of the study sample scoring in the severe sleep Canadian children.
disturbance range. Children with ADHD and ABPM abnor- Despite the small sample, results of this study suggest that
malities (except nondipping) were 5.6-fold more likely to score the ‘white coat’ phenomenon is largely responsible for elevated
above 39 > on the SDSC than those without ABPM abnormali- office blood pressure in children medicated for ADHD. Studies
ties (OR 5.6, 95% CI: 1.25 to 24.95; P=0.02), when controlling involving otherwise healthy children suspected of hypertension
for BMI, age and sex. Similarly, children who had nondipping on based on office measurements, found white coat hypertension
ABPM were at five times the odds of having a sleep disturbance (WCH) in up to 50% of cases (32,33). In children, WCH was
(SDCS score > 39) than their peers who did not experience found to be associated with higher BMIs and higher left ventric-
nondipping (OR 5.13, 95% CI: 1.1 to 23; P=0.03) controlling ular mass which was still present even after adjusting for body
for age, sex and BMI. mass index while in adults WCH is considered as a risk factor
for cardiovascular events (34,35). The significance of WCH in
children medicated for ADHD, who seem to have a tendency
DISCUSSION for lower BMIs, is not known.
This small prospective observational study provides reassuring The clinical significance of the very high risk for sleep non-
evidence regarding the risk for clinically significant hyperten- dipping discovered by ABPM screening is also not well defined.
sion in children medicated for ADHD. As anticipated, ADHD In children with diabetes, sleep nondipping was associated
pharmacotherapy was associated with more prevalent elevated with increased risk for BP related target organ damage while in

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Table 2. Classification of office BP values in combination with ABPM results and frequency of sleep disturbances in children with ADHD
Classification based on a single office BP and ABPM results* N=55 (100%)
Normal BP (Office BP 90th percentile, ABPM average <95th percentile, Load <25%) 39 (70.9%)
White Coat HTN (Office BP ≥95th percentile, ABPM average <95th percentile, Load <25%) 3 (5.45%)
Pre-HTN Office (Office BP ≥90th percentile, ABPM average <95th percentile, Load ≥25%) 0
Masked HTN (Office BP <95th percentile, ABPM average >95th percentile, Load ≥25%) 2 (3.64%)
Ambulatory HTN (Office BP >95th percentile, ABPM average >95th percentile, Load 25–50%) 0
Unclassified 1 (Office BP ≤90th percentile, ABPM average <95th percentile, Load ≥25%) 6 (10.9%)
Unclassified 2 (Office BP ≥90th<95th percentile, ABPM average <95th percentile, Load <25%) 5 (9.1%)
Non-dipping (Mean sleep/(Mean wake – 0.1*Mean wake) > 1.0) 28 (50.91%)
Sleep disturbance based on a score > 39 on the SDSC questionnaire 43 (78.2%)

*Based on Flynn et al. (22).

ABPM Ambulatory blood pressure monitoring; ADHD Attention deficit/hyperactivity disorder; BP Blood pressure; HTN Hypertension; SDSC Sleep
disturbance scale for children

adults it has been shown to be associated with all-cause mor- aim of the present study was to capture a ‘real life’ sample of
tality (36,37). Overweight and obesity have also been found children medicated for ADHD rather than focus on the effect
to be associated with higher prevalence of nondipping in up to of a specific drug. This approach has the potential to provide
42% of prepubertal and early pubertal severely obese children more accurate answers to general questions related to BP, in
(37). The pathophysiologic mechanism of nondipping is likely children with ADHD given an increasing variety of available
multifactorial and currently poorly defined, however sleep dis- medications and a well-documented tendency of physicians
turbances and autonomic nervous system imbalance have been and patients to try different approaches and make frequent
implicated (36). Both these mechanisms have been associated dosage changes while monitoring clinical improvement of
with ADHD and have also been shown to be influenced by psy- symptoms (43,44).
cho-stimulant agents (38–42). In summary, we prospectively examined blood pressure
The SDSC demonstrated the fact that sleep disturbances values measured during a single screening office visit and by
are prevalent in children medicated for ADHD and a statisti- ABPM in a sample of children with ADHD from a large com-
cal correlation with sleep nondipping and other sleep ABPM munity paediatric clinic. Compared to screened children in the
abnormalities was identified, but the study was not designed to general Canadian population, this cohort demonstrated higher
prove or search for causality. Furthermore, as with WCH, the prevalence of office BP values in the hypertension or prehyper-
significance of nondipping in this population is not known and tension range despite having a lower average BMI compared
is likely to be different than in populations with multiple cardio- to children in the general Canadian population. Ambulatory
vascular risk factors such as diabetes and overweight. monitoring did not confirm a high prevalence of clinically
The study was limited by the relatively small sample of par- significant hypertension in these children but suggested more
ticipating children, the convenience bias related to recruitment frequent occurrence of ‘white coat’ hypertension as well as a
from a single clinic and lack of a well-matched control group common loss of the typical circadian BP pattern of sleep dip-
of nonmedicated children with ADHD. The use of the CMHS ping. These findings support current American Academy of
cohort as control representing the general population was less Pediatrics recommendation for careful longitudinal follow-up
than ideal in view of the variability in the number of BP mea- of children medicated for ADHD, including more frequent
surement. Nevertheless, this was a relatively unique attempt office BP monitoring; however, their long-term clinical signif-
to define BP at rest and on ambulatory monitoring in a ran- icance is unknown. Longitudinal long-term studies focusing on
dom sample of children with ADHD treated in the community the effect of childhood initiated ADHD pharmacotherapy on
with a variety of medications indicated for ADHD. Previous BP and cardiovascular outcomes will be required to eliminate
prospective small studies with rigorous cross-over design have such knowledge gaps.
proven beyond doubt that stimulant medications treatment in
children is associated with a statistically significant elevation Acknowledgments
in ABPM values (13,14). However, these studies that focused We thank our colleagues from the Kaleidoscope Pediatric Consultants
exclusively on the effect of one or two psychostimulant agents Clinic in Calgary, Dr. Kate N. Culman, Dr. Jennifer R. MacPherson and
did not demonstrate that this effect is also clinically significant Dr. Darrell J. Palmer for their support and collaboration that made this
or is associated with increased prevalence of hypertension. The project possible.

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Funding Source: This research was partially supported by a ‘Small 13. Samuels JA, Franco K, Wan F, Sorof JM. Effect of stimulants
Research Grant’ from the Alberta Children’s Hospital Research on 24-h ambulatory blood pressure in children with ADHD:
Institute and a Markin Undergraduate Student Research Program in A double-blind, randomized, cross-over trial. Pediatr Nephrol
Health & Wellness summer student scholarship. 2006;21(1):92–5.
Financial Disclosure: The authors have no financial relationships rele- 14. Stowe CD, Gardner SF, Gist CC, Schulz EG, Wells TG. 24-hour
vant to this article to disclose. ambulatory blood pressure monitoring in male children receiving
stimulant therapy. Ann Pharmacother 2002;36(7-8):1142–9.
Conflict of Interest 15. Wernicke JF, Faries D, Girod D, et al. Cardiovascular effects
The authors have no conflicts of interest relevant to this article to of atomoxetine in children, adolescents, and adults. Drug Saf
disclose. 2003;26(10):729–40.
16. Wilens TE, Biederman J, Lerner M. Effects of once-daily osmotic-re-
lease methylphenidate on blood pressure and heart rate in children
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