Download Prevalence and Consequence of Systolic Hypertension in Children

AJH
2002; 15:57S– 60S
Prevalence and Consequence of
Systolic Hypertension in Children
Jonathan M. Sorof
Systolic blood pressure (SBP) has become the major criterion for the diagnosis, staging, and treatment of hypertension in adults, based on the epidemiology and pathophysiology of adult hypertension, linkage between SBP
levels and disease, and benefits of treatment of isolated
SBP hypertension. Although children do not typically
suffer overt hypertensive disease, an accumulation of data
suggests that SBP elevation is as important a factor in the
morbidity of hypertension in children as in adults. Systolic
BP hypertension is more common in children, whether
examining an unselected sampling of patients by routine
screening or a selected sampling of referred hypertensive
patients. Mild-to-moderate BP elevation in children is
associated with increased left ventricular mass (LVM),
T
he diagnosis, staging, and therapeutic management
of adult hypertension have undergone a major shift
in emphasis in recent years toward systolic blood
pressure (SBP). This shift is best illustrated by the most
recent clinical advisory statement from the Coordinating
Committee of the National High Blood Pressure Education
Program.1 Citing lines of evidence included data on the
epidemiology of systolic and diastolic hypertension, the
pathophysiology of adult hypertension, the linkage between SBP levels and disease, and the relative benefits of
treatment of isolated systolic hypertension, the advisory
statement prioritizes SBP and specifically states, “the use
of age-adjusted BP targets is discouraged.” This emphasis
on SBP in adults is of uncertain applicability to the evaluation and management of hypertension in children. Ageadjusted BP targets must be used in children due to the
normal age-related increase in BP throughout childhood.
Atherosclerotic disease and overt cardiovascular morbidity or mortality are uncommon in the vast majority of
hypertensive children, thereby preventing linkage of
treated or untreated mildly to moderately elevated BP with
outcome. Despite these limitations, an accumulation of
data now suggests that SBP elevation is as important a
factor in the morbidity of hypertension in children as in
Received October 15, 2001. Accepted October 16, 2001.
From the Section of Nephrology and Hypertension, Department of
Pediatrics, University of Texas-Houston School of Medicine, Houston,
Texas.
© 2002 by the American Journal of Hypertension, Ltd.
Published by Elsevier Science Inc.
with SBP more closely linked to LV morphology than
diastolic BP (DBP). Furthermore, SBP is associated with
increased LVM even in patients with SBP within the
normal range. Among hypertensive children, the reported
prevalence of left ventricular hypertrophy (LVH) ranges
from 30% to 70%, and LVH is more closely related to SBP
than to DBP. These data suggest that treatment of hypertension should be directed at normalization of SBP, even
when DBP is within the normal range. In addition, trials of
antihypertensive medications in children should incorporate SBP hypertension into study inclusion criteria. Am J
Hypertens 2002;15:57S– 60S © 2002 American Journal of
Hypertension, Ltd.
Key Words: Systolic hypertension, children, sequelae.
adults. The goal of this review is to provide support for
this statement by summarizing studies on 1) the prevalence of SBP hypertension in healthy and hypertensive
children, and 2) the relationship between SBP and indexed
left ventricular mass or left ventricular hypertrophy (LVH)
in healthy and hypertensive children.
Prevalence of SBP
Hypertension in Healthy
and Hypertensive Children
The relative importance of SBP and diastolic blood pressure (DBP) hypertension in children can be expressed in
part by their respective prevalences in healthy and hypertensive pediatric populations. Several screening programs
have determined the prevalence of hypertension in an
unselected population of otherwise healthy school-aged
children. Using varying diagnostic thresholds and number
of visits to define hypertension, the range reported from
several large BP screening studies is a three- to eightfold
higher prevalence of systolic than diastolic hypertension.2– 4 These single-center studies are limited by their
concentration on a single geographic region. A recent
multicenter collaborative study on ethnic differences in BP
Address correspondence and reprint requests to Dr. Jonathan M.
Sorof, Division of Pediatric Nephrology and Hypertension, University of
Texas-Houston, Medical School, Room 3.124, 6431 Fannin Street, Houston, TX 77030; e-mail: [email protected]
0895-7061/02/$22.00
PII S0895-7061(01)02303-2
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SYSTOLIC HYPERTENSION CONSEQUENCES IN CHILDREN
in children by Rosner et al5 reviewed the data from eight
large studies from 1978 to 1991 from different geographic
regions in the United States. Overall, SBP data on 47,196
children (68,556 visits), and DBP based on the fifth
Korotkoff sound (K5) data on 38,184 children (52,053
visits) were available. Using definitions from the Task
Force Report on High Blood Pressure in Children and
Adolescents6 and after pooling the data from all visits, the
overall prevalence of SBP hypertension was 4.4% and of
DBP hypertension was 3.2%. Further analysis shows that
the prevalence of SBP hypertension was higher for virtually every grouping of subjects by race, gender, and age.
Thus, the prevalence of SBP hypertension in a healthy,
unselected, and geographically diverse population of children was approximately 1.4 times that of DBP hypertension. Although these studies are consistent in showing a
higher prevalence of SBP hypertension, controversy over
the choice of the onset of the fourth Korotkoff sound (K4)
or K5 for determining DBP in children and discrepancies
in the prevalence of diastolic hypertension based on that
choice may have important implications for comparing
studies and determining the relative prevalences of SBP
and DBP hypertension.7
The 1997 Food and Drug Administration Modernization Act has resulted in a substantial increase in pediatric
trials of antihypertensive medications.8 One of the first
was the Ziac Pediatric Hypertension Study, a multicenter
study conducted through subject recruitment from 22 centers in the United States and Brazil that care for children
with hypertension.9 To qualify for randomization to treatment or placebo, subjects were required to have an average
sitting SBP or DBP above the Task Force 95th percentile
at the last visit of the screening placebo phase. One hundred forty children were initially screened for the study,
and 110 children qualified for randomization. At the initial
screening visit, 71% of subjects had systolic hypertension
(isolated or in combination with DBP hypertension) and
51% had diastolic hypertension (isolated or in combination with SBP hypertension). At randomization, 83% had
systolic hypertension and 53% had diastolic hypertension.
Among the randomized patients, the prevalence of isolated
SBP hypertension was 47% compared to a prevalence of
isolated DBP hypertension of only 17%.
Transient psychological stress, which may occur when
a patient is confronted by an unfamiliar medical setting,
may preferentially elevate SBP and thus may overestimate
the prevalence of SBP hypertension by casual BP measurement in the clinic setting. To determine whether SBP
elevation to the hypertensive range in children undergoing
hypertension assessment is transient or persistent, Sorof
and Portman10 reviewed 115 children referred by primary
care providers for persistent casual BP elevation who
underwent 24-h ambulatory BP monitoring as part of the
initial diagnostic assessment. For the entire patient group,
the prevalence of hypertension by normative pediatric
ambulatory BP criteria was 44% for SBP and 23% for
DBP. Among the patients with documented casual hyper-
AJH–February 2002–VOL. 15, NO. 2, PART 2
tension in the hypertension clinic, the prevalence of ambulatory hypertension was 95% for SBP and 35% for
DBP. Thus, similar to the unselected screening population,
the prevalence of SBP hypertension in selected referral
population was higher than that of DBP hypertension.
SBP and Left Ventricular
Morphology in Normotensive
and Hypertensive Children
The recommendations regarding the threshold values for
defining hypertension in adults are based on the associations between BP values that exceed these thresholds and
subsequent morbidity or mortality. These associations are
difficult to establish in children as overt morbid events
such as stroke, myocardial infarction, and congestive heart
failure are rare except in cases of severe hypertension. In
the absence of these events, the most extensively investigated surrogate marker of hypertensive morbidity in children has been the geometry and size of the left ventricle
measured by M-mode echocardiography. Virtually all of
the studies of children have found that SBP is positively
associated with left ventricular mass (LVM). Burke et al11
from the Bogalusa Heart Study reported in 654 healthy
subjects aged 7 to 22 years that after adjustment for body
size, LV wall thickness and the ratio of LV thickness to
chamber size were found to be correlated with SBP but not
with DBP. Similarly, Malcolm et al12 from the Muscatine
Study reported in 904 normal patients aged 6 to 16 years
that a strong positive linear association was found between
LVM and both SBP and DBP. Daniels et al13 examined
the relationship of LVM to BP in 201 normotensive subjects aged 6 to 17 years old and found that SBP and DBP
were significant univariate correlates of left ventricular
mass. However, multiple regression analysis revealed that
only lean body mass, fat mass, and SBP were statistically
significant independent correlates of LVM. Treiber et al14
investigated the association between LVM index (LVMI)
and BP in 84 biracial normotensive children selected for a
family history of hypertension. Significant independent
correlates with LVMI included resting SBP but not DBP.
Harshfield et al15 performed BP assessment and echocardiography in 60 African American and 40 white normotensive youths. Sex, age, and SBP were independent predictors in the sample as a whole, accounting for 37% of the
variance of LVMI. Thus, the results from all these studies
indicate a clear independent association between SBP and
LV morphology, even in healthy children without known
elevation of BP to the hypertensive range.
The ability of current BP to predict future LV morphology has also been investigated in normotensive children.
Papavassiliou et al16 assessed the contributions of anthropometric, demographic, and cardiovascular parameters as
predictors of LVM 3 to 4 years after the initial examination in 68 children. The only cardiovascular parameter that
predicted LVMI was SBP reactivity to postural change.
AJH–February 2002–VOL. 15, NO. 2, PART 2
SYSTOLIC HYPERTENSION CONSEQUENCES IN CHILDREN
Kapuku et al17 performed a similar study in 146 youths on
two occasions separated by 2.3 years using both clinic and
ambulatory BP. The SBP response to stress and initial
ambulatory SBP (24-h, daytime, and nighttime) was positively related to the LVMI measured 2 years later. These
data suggest that both enhanced SBP reactivity to stress
and elevated resting ambulatory SBP are predictive of
future LVMI and, by extension, the development of LVH.
The same relationship between SBP and LVM has been
demonstrated in hypertensive children. Daniels et al18
studied 104 children and adolescents with BP persistently
more than the 90th percentile for age and sex who had no
known cause of BP elevation. The LVH (defined as LVMI
more than the pediatric 95th percentile) was found in
38.5% of patients. Resting SBP was a significant univariate correlate with LVMI, whereas DBP was not. Multiple
regression showed that independent correlates of LVMI
were male sex, body mass index, sodium intake, age, and
SBP at maximal exercise. Chamontin et al19 studied 49
young adults (⬍20 years of age) with a history of childhood hypertension detected at a routine school physical
examination and 49 young adults with BP more than the
97.5th percentile. All subjects underwent measurement of
ambulatory wake BP by oscillometric monitoring, a 15min oscillometric BP monitoring in clinic, and measurement of clinic office BP with a standard mercury sphygmomanometer. Significant correlates of LVMI were
ambulatory wake SBP and mean oscillometric SBP. The
LVMI did not correlate with office SBP, and did not
correlate with any DBP parameter. Belsha et al20 performed ambulatory BP monitoring and M-mode echocardiography in 33 normotensive and 29 untreated mildly
hypertensive adolescents. The prevalence of LVH in the
hypertensive group was 34%. Overall, sleep SBP correlated most closely with LVMI. Other significant univariate
correlates were casual SBP and DBP, and 24-h and wake
SBP (r ⫽ 0.32– 0.40). None of the ambulatory DBP parameters correlated with LVMI.
In conclusion, the paradigm of essential hypertension in
adults has clearly shifted to an emphasis on SBP. The SBP
hypertension in older patients is more common, is a
marker for vascular disease, predicts cardiovascular morbidity and mortality, and when treated results in decreased
morbidity and mortality. In children and adolescents, data
supporting a similar pattern of disease is emerging. The
SBP hypertension is more common in children, whether
examining an unselected population of patients by routine
screening or a selected population of referred hypertensive
patients. In addition, compelling evidence in children suggests that even mild-to-moderate BP elevation is associated with increased LVM, and that SBP appears to be
more closely linked to LV morphology than DBP. This
association persists even when controlling for other variables such as age and body habitus. Among patients with
casual hypertension by Task Force criteria, the reported
prevalence of LVH defined by pediatric standards ranges
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from 30% to 70% and is more closely related to SBP than
to DBP. Increased LVM is associated with SBP even in
patients whose SBP falls within the “normal” range.
In aggregate, these data indicate that SBP hypertension
in children should be considered to be of primary prognostic significance. This assertion has practical implications. Treatment of hypertension should be directed at
normalization of SBP, even when DBP is within the normal range. Trials of antihypertensive medications in children should incorporate SBP hypertension into the study
inclusion criteria. Future pediatric studies should be aimed
at demonstrating regression of LVM with effective treatment of both SBP and DBP elevation, and at prevention of
cardiovascular morbidity by early initiation of such treatment. If physicians who care for hypertensive children
seek to promote health that extends beyond the traditional
pediatric age range, early recognition and intervention for
hypertension clearly must begin in childhood.
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