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sium intake and cardiovascular reactivity in

with risk factors for essential hypertension


roof MD, Alex Forman, PA, MeH, Nancy Cole, BA, John M. Jemerin, MD, and
t~ Curtis Morris, MD

Objectives: Our study objectives were as follows: (1) to determine whether urinary Both genetic and environmental factors may
excretion of potassium is lower in black than in white children, (2) to determine participate in the pathogenesis of essential
whether cardiovascular reactivity (CVR) varies inversely with dietary intake of potas- hypertension. The risk of essential hyperten-
sium, and (3) to confirm that CVR is greater in black than in white children, and in sion is greater in black subjects than in white
subjects 1, 2 and in individuals who have a
children with a family history of hypertension than in those without such a history.
family history of hypertension than in those
Study design: Baseline measurements included 2 4 - h o u r urinary sodium, potassium, with no such history. 3-5 In normotensive
and ereatinine levels and food intake (by questionnaire). Resting and stress blood pres- children and adults, both risk factors have
sures were measured during blood sampling, cold water foot immersion, and a video been associated with an acute cardiovascu-
game before and after 1 week each of supplementation with potassium citrate, 1.5 lar response to stress that is enhanced, T M
mmol/kg per day, and placebo administered in random order. which itself may predict higher resting blood
pressure values and the occurrence of essen-
Results: Thirty-nine children aged 7 to 15 years were studied. White subjects had
tial hypertension. 22"25 Such enhancement
higher baseline excretion of potassium than black subjects (p < 0.001) and higher veg-
may be so predictive because the increased
etable intake (p < 0.01), which were positively correlated (r = 0.53, p < 0.001). At base- adrenergic activity that mediates it26' 27 may
line, the 24-hour urinary potassium/creafinine ratio varied inversely with diastolic CVR be an important pathogenetic determinant of
to the video game stressor in white children (r = -0.55, p = 0.02). Cardiovascular reac- essential hypertension. 28 Thus black race
tivity was not attenuated measurably by potassium supplementation compared with and a positive family history of hypertension
placebo. The CVR was greater in children with a family history of hypertension than in might both be risk factors for hypertension
those without, but was not greater in black children than in white children. in part through the agency of enhanced
adrenergic activity.
{2onlusions: The urinary potassinm/creatinine ratio is higher in white than black chil-
dren because their intake of vegetables is greater; dietary potassium intake may modu-
late CVR, particularly in white children with a family history of hypertension, but may
need to be supplemented for more than 1 week to demonstrate attenuation of CVR;
and a family history of hypertension may be a stronger predictor of enhanced CVR
than is race. (J Pediatr 1997; 131:87-94)

From the Departments of Pediatrics,Medicine, and Radiology, and GeneralCh)zicalResearch Center, Universityof In short-term studies of both hyperten-
California- San Francisco. sive aduks and normotensive young adults
Supported in part by giftsfrom the Church and Dwight Corporationand the EmilMossbacher,Jr. with F H +, adrenergically mediated car-
Foundation; U.S. PublicHealth Service,NationalHeart Lung and BloodInstitute grant No. RO1- diovascular phenomena are enhanced by
HL47943; and grant No. 5 MO1 RR-00079 from the GeneralClinicalResearchCenter and Pediatric potassium restriction and attenuated by its
ClinicalResearch Center, Divisionof Research Resources,Universityof California-San Francisco.
supplementation for periods of 6 to 14
Submittedfor publicationJune 11, 1996; acceptedNov. 18, 1996.
clays.29-31 Supplementation of dietary
Reprint requests:Jonathan Sorof, MD, Texas Children'sHospital,6621 Fannin St. MC 3-2482, Houston,
TX 77030-2399. potassium can abolish the racial differ-
Copyright 1997by Mosby-YearBook, Inc. ences (black vs white) in cardiovascular
0022-3476/97/$5.00 + 0 9/21/79369 reactivity to stress in previously potassi-

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SOROF ET AL. THE JOURNAL OF PEDIATmCS
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Table L Clinical and physiologic characteristics of subjects at baseline METHODS


Subject Recruitment
Subjects were recruited from the San
Francisco area by circulation of flyers to
local schools and to local pediatric clinics
affiliated with the University of Califor-
n i a - S a n Francisco. Inclusion criteria
were as follows: 7 to 15 years of age, black
or white race (each of four grandparents
of same self-described ethnicity as the
subject), normal serum concentration of
creatinine, and no concurrent medication
use during the duration of the study.
Subjects were categorized by the pres-
ence or absence of a family histo W of es-
Table IL Relationship of urinary electrolytes and food frequency to race and family his- sential hypertension (defined as at least
tory of hypertension one parent or grandparent with essential
hypertension by parental report). Es-
sential hypertension was defined as hy-
pertension in the absence of secondary
causes such as primary renal disease or di-
abetes, or that developed before the age of
65. Consent forms for parents and age-ap-
propriate assent forms for subjects were
approved b y the Committee on Human
Research at the University of Califor-
nia-San Francisco and were signed at the
first visit. Each subject received $120 re-
imbursement for completing the 2-week
study.

Hemodynamic Measurements
and Experimental Stressors
Three visits, 1 week apart, were made
urn-restricted, normotensive men, 52 re- subjects and in F H individuals, and to the Pediatric Clinical Research Center
duce blood pressure in adults with essen- thereby increase their risk of hyperten- at Moffitt Hospital. At each visit, the sub-
tial hypertension, 33-39 and slow the nor- sion. To further consider this hypothesis, jects were seated in a quiet, darkened
mal age-related rate of rise of blood we determined the following in nor- room and a blood pressure cuff was
pressure in adolescent girls who follow motensive children: (1) whether dietary placed on their left arm. After a S-minute
salt-restricted diets,g0 Urinary excretion intake and urinary excretion of potassium rest period during which the subject
of potassium is inversely related to (1) are less in black children than i n white watched an age-appropriate videotape,
resting blood pressure in adults, (2) the children on the West coast, (2) whether four blood pressure and heart rate mea-
rate of the age-related rise of blood pres- the acute cardiovascular response to surements were made 1 minute apart with
sure in normal children, and (3) the inci- stress varies inversely with urinary excre- an oscillometric device (Dinamap, John-
dence of essential hypertension, 41-45 and, tion of potassium, (3) whether dietary son & Johnson Medical, Inc.). The final
in the United States, is lower in black potassium supplementation can attenuate three of four sets of measurements were
subjects than in white subjects beginning an enhanced cardiovascular response, averaged to give the resting hemodynam-
in childhood. 11, 46-50 Accordingly, a long- and (4) whether the acute cardiovascular ic measurements for that visit.
term reduced dietary intake of potassium response to stress is greater in black chil- After the resting hemodynamic mea-
might enhance adrenergic-mediated car- dren than in white children, and in chil- surements were made, three different ex-
diovascular phenomena over the long dren with F H than in children with no perimental stressors were administered:
term, particularly in n0rmotensive black family history of hypertension. blood sampling, cold pressor, and video

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THE JOURNAL OF PEDIATRICS SOROF ET AL.
Volume 13 I, N u m b e r I, Part I

game. Blood sampling refers to the stress


associated with the anticipation of phle-
0.1 !
botomy. Subjects were told that blood o
o o
was about to be obtained with a needle,
o o o
a 23-gauge butterfly needle was pre-
pared for use, and an alcohol wipe was
0.08
applied to the skin. Immediately before
the insertion of the needle, two consec- 0
utive hemodynamic measurements were E 0.06
recorded and blood was then obtained.
This was followed by a 5-minute rest
E
period. Coldpressor refers to the stress of
immersing an extremity in a cold water
L_ "D 2 ~ 00
bath. Subjects were asked to immerse a
0 0.04
foot up to the ankle into a 10" C (50 F) o

water bath for as long as they could en- 0

dure for up to 1 minute, but were told


that the foot could be removed at any 0.02
time. Hemodynamic measurements
were made and recorded at 15 and 45 r = 0.53, p <0.001
seconds of foot immersion. The foot was
removed at 1 minute and immediately 0 , t , I

warmed and dried. This was followed 0 400 800 1,200 1,600
by a 5-minute rest period. Video game
refers to the stress associated with play-
Vegetable Intake (portions/year)
ing a computer game for financial incen-
tive. Subjects played a 4-minute stan-
dardized computer memory game that
White (n=17) Black (n=19)
0
required memorizing a random se-
quence displayed on the computer
screen and then reproducing it by press- F~g. I. Relationship between vegetable intake and urinary excretion of potassium. Open
ing keys on the keyboard in the same se- circles, white subjects; solid circles,black subjects.
quence. This video memory task was se-
lected because of its high test-retest
reliability as described elsewhere, sl For sisted by their parents. The number of study, subjects were randomly assigned
each correct response, subjects received portions per year of each food on the list to receive either an oral solution of potas-
25 cents up to a total of 5 dollars per was calculated to provide a yearly fre- sium citrate, 1.5 mmol/kg per day in 2 di-
game. Hemodynamic measurements quency for each individual food. Each vided doses, or a solution of cherry syrup
were made and recorded after 30 sec- food was assigned to one of four main placebo. During the second week of the
onds and then every 1 minute thereafter food categories (meats, vegetables, study, the supplement was switched to
for a total of 4 sets of measurements. fruits, and dairy), and each category was the one not yet received, so that on com-
The order in which the stressors were then expressed in portions per year. pletion of the study each subject had re-
administered was the same for each Portions per year of meats, vegetables, ceived 1 week of both potassium and
study visit. fruits, and dairy were compared for placebo. Both the subjects and the inves-
black and white children, and for F H - tigators were unaware of the order of ad-
Dietary Questionnaires and F H children. ministration of the solutions. The potas-
A list was compiled of the foods that sium citrate solution was diluted 2:1 with
comprise the top 50 sources of potassium Potassium Supplementation cherry syrup to mask the taste of the sup-
in the American d i e t 9 Subjects were Before the first study visit, each sub- plement, and the placebo solution was
asked to report the frequency of intake of ject collected urine for 24 hours; the sam- diluted 2:1 with 1% acetic acid to give a
each food on the llst by clay, week, month, ples were analyzed for the concentra- slightly bitter taste. Compliance was as-
or year. Subjects who could not complete tions of sodium, potassium, and sessed by measuring the residual vol-
the questionnaires by themselves were as- creatinine. During the first week of the umes in the bottles of supplement at the

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SOROF ET AL. THE JOURNALOF PEDIATRICS
JULY 1997

Table IIL Cardiovascularreactivity stressors at baseline

end of each week, and by 12-hour RESULTS dren than in black children (722 vs 392,
overnight urine collections on the even- p < 0.01). The portions per year of meats,
ings before both the second and third Subject Demographics fruits, or dairy products did not differ be-
study visits. Thirty-nine children (22 girls, 17 boys) tween black and white children. Vege-
completed the study from June 1994 to table intake correlated positively with 24-
Data Analysis November 1994. Four other children hour UK+/Cr (r = 0.53,p < 0.001) (Fig. 1),
For each experimental stressor, CVR were not included in the study because and negatively with 24-hour urinary sodi-
was expressed as both the maximum he- they did not comply with the supplemen- um/potassium ratio (-0.37, p < 0.05). The
modynamic response, and as the change tation solutions. Race, family history of 24-hour UNa+/Cr did not correlate with
from the resting state to the maximum re- hypertension, and sex were evenly dis- portions per year of vegetables, meats,
sponse for systolic blood pressure, dias- tributed in the study group, and age, fruits, or dairy products.
tolic blood pressure, mean arterial pres- weight, and resting hemodynarnic para-
sure, and HR. Urinary electrolyte values meters at the first visit did not differ be- Cardiovascular Reactivity to
were expressed as milliequivalents per tween black and white children, or be- Stressors at First Visit
milligram of creatinine. Dietary frequen- tween F H - and F H + children (Table I). For each experimental stressor, SBP,
cies were expressed as portions per year. None of the children was hypertensive at DBP, MAP, and H R were compared with
A two-tailed t test was used for racial rest by commonly accepted defmitions of respect to race and family history of hy-
(black vs white children) and family his- hypertension in children. The prevalence pertension (Table III). In F H children
tory of hypertension (FH- vs F H ) com- of a family history of hypertension did not compared with F H - children (Table III),
parisons. A Spearman correlation test as- differ between black and white subjects. blood sampling induced a marginally
sessed the association between 26-hour greater change in SBP (p = 0.055), and
baseline urinary potassium/creatinine Urinary Electrolyte Levels and the video game stressor induced a
ratio and both food portions peryear and Dietary Questionnaire greater change in SBP (p < 0.05) and
stress cardiovascular responses. Analysis The 24-hour UK+/Cr was greater in MAP (p < 0.05). White and black children
of variance for repeated measures was white children than in black children did not differ in the change in cardiovas-
used to compare the cardiovascular re- (0.062 vs 0.041, p < 0.001), and the 24- cular response induced by any of the ex-
sponse for the study periods of baseline hour urinary sodium/potassium ratio was perimental stressors (Table II D. In white
versus placebo versus potassium for each greater in black children than white chil- children (n = 17), the 24-hour UK/Cr
subject. All statistical analyses were per- dren (3.96 vs 2.51, p < 0.001)(Table II). showed a negative correlation with the
formed with the STATISTICA for The 24-hour urinary sodiurn/creatinine maximum D B P induced by the video
Windows software package (release 4.3, ratio was not different between black and game stressor (r = -0.55, p = 0.02) (Fig. 2),
StatSoft, Inc.). Data are expressed as white children. The portions per year of and marginally negative correlations with
mean SD. vegetables was greater in white chil- the maximum D B P induced by blood

90
THE JOURNAL OF PEDIATRICS SOROF ET AL.
Volume 13 I, N u m b e r I, Part I

sampling @ = -0.44, p = 0.08), and the 90


maximum MAP induced by cold pressor
(r = -0.48, p = 0.06). In white FH +children
(n = 7), the 24-hour UK+/Cr showed a
negative correlation with the maximum
DBP induced by video game (r = -0.82, 80
p < 0.05) (Fig. 2) and by blood sampling (r .... .. O
= -0.79, p < 0+05), and a marginally nega- %"'%%
tive correlation with the maximum DBP (r "%%oo O
= -0.70, p = 0.08) and the maximum MAP E
(r = - 0 . 7 5 , / 9 = 0.052) induced by cold E 70
pressor. Cold pressor induced the great- O
0_
est change in SBP (p < 0.05), DBP (p < m
0.001), and MAP (p < 0.05) cardiovascu-
lar responses of the three stressors (Table X O "-.O
IV). 60
O "~
Potassium Supplementation
The UK+/Cr value was significantly
higher during the potassium supplementa-
tion period than during either the baseline 50 O
or placebo period (p < 0.001) for all sub-
jects (Table IV). The cardiovascular re- r , I , I
sponse to blood sampling was higher dur- 0.02 0.04 0.06 0.08 0.1
ing the baseline period than during either
the placebo or potassium periods for the UK/Cr (meq/mg)
change in SBP, DBP, and MAP (0 < 0.06)
(Table IV). The cardiovascular response White (n=17) White FH+ (n=7)
to the video game stressor was higher dur-
r = - 0.55, p = 0 . 0 2 r = -0.82, p = 0.03
ing the baseline period than during the
placebo or potassium periods for the
change in SBP, DBP, and MAP (o < 0.05).
The cardiovascular response to cold pres- F ~ . 2. Relationshipbetween maximum changein diastolicblood pressureto video game
stressor and urinary excretion of potassium.Open circles and dashed line, white subjects;
sor did not differ among the baseline,
solid drcles and solid line, white subjectswith family history of hypertension.
placebo, or potassium periods. For each of
the stressors, the placebo and potassium
periods did not differ in the change in
CVR when considering all subjects, the Several studies have found that black sub- the lower urinary excretion of potassium
subsets of white and black children, the jects consume fewer potassium-contain- in the black children.
subsets of FH- and FH + children, and the ing foods such as fruits and vegetables White F H children had a lower base-
children who excreted less than the mean than do white subjeetsfi 346 By using a line 24-hour UK/Cr than the white F H -
24-hour UK/Cr at baseline. food frequency questionnaire, an instru- children. In the white children, particular-
ment that has been shown to be reliable in ly in those who were FH , many of the
the study of dietary habits in children, 56' 57 maximum cardiovascular responses at the
we found that the frequency of intake of first visit varied inversely with the base-
DISCUSSION vegetables in black children was approxi- line 24-hour UK+/Cr. This observation is
Despite its small number of subjects, mately half that of white children, where- entirely consistent with the findings in
our study confirms that black children ex- as the intake of meats, fruits, or dairy studies of white normotensive young
crete less potassium but similar amounts products did not differ. The positive cor- adults that supplementation of dietary
of sodium compared with white chil- relation between vegetable intake and 24- potassium in those subjects who were
dren, ll, 46-50 and documents the occur- hour UK+/Cr suggests that the lower in- FH + attenuates acute adrenergically me-
rence of this phenomenon in a population take of potassium-containing foods such diated cardiovascular phenomena. 29' 50
of children living on the West coast. as fresh vegetables accounts for much of We also confirmed that the acute car-

91
SOROF ET AL. THE JOURNAL OF PEDIATRICS
JULY 1997

Tab& ~ Cardiovascular reactivity and urinary electrolyte levels for each study period were not different from those who re-
ceived placebo, irrespective of experimen-
tal stressor. To demonstrate attenuation of
the cardiovascular response to stress after
an intervention requires that the response
to that stress be highly reproducible with-
in the same individual throughout the du-
ration of that intervention. Several studies
in children and young adults have found
high test-retest reliability of acute cardio-
vascular response within individuals to
various experimental mental and physical
stressors.24, 51, 62-65 However, the applica-
bility of these results to the current study
is rendered uncertain by both the sub-
stantially longer interval between tests in
most other studies, and the limits of in-
traindividual test-retest reliability. If the
acute cardiovascular response to a stres-
sor depends on the level to which the sub-
ject subjectively experiences acute anxi-
ety, fear, or discomfort, then a decrease in
the intensity of that subjective experience
would tend to attenuate subsequent re-
diovascular response to stress was vs 19). However, we neither have nor sponses and thereby decrease the test-
greater in F H + children than in F H - know of data that compare the acute car- retest correlation. Particularly for the
children 6, 8, 10, 12, 18, 20; however, this diovascular response to cold stimulus to mental stressors, a shorter interval be-
greater cardiovascular response in F H + the face with that to the foot in either tween testing periods might speed the ha-
children was significant only in the white black or white children to support this hy- bituation to these stressors and lead to de-
subjects. Some studies, 11' 58, 59 but not pothesis. terioration in the test-retest reliability.
others,60, 61 have found greater CVR in After the first visit, repeated exposure Although the video game task used in the
F H + black children than in F H - black to either blood sampling or the video current study was reported to have signif-
children. game stressor at 1-week intervals was as- icant test-retest correlations in young
In the current study, although black chil- sociated with a decreased cardiovascular adults of 0.87, 0.69, and 0.59 for HR,
dren did not have a greater cardiovascular response, independent of whether potassi- SBP, and DBP, respectively,51 these cor-
response than white children as has been um or placebo was supplemented. By relations may not be high enough to
reported in other studies, 7' 9, 11, 15-17, 19 a contrast, the cardiovascular responses to demonstrate that potassium supplementa-
trend toward a greater response to cold cold pressor did not change with repeated tion can attenuate the acute cardiovascu-
pressor was observed in black children. A exposure. Habituation therefore appeared lar response to stress with the study de-
power analysis of our current data indi- to have occurred with the mental stres- sign w e used.
cates that approximately 100 black and sots, but not with the physical stressor. Potassium supplementation may have
100 white children would have to be stud- The video game stressor did not induce ei- failed to measurably attenuate CVR for
ied to detect a significant difference in the ther as great an H R response as did blood other reasons. Subjects may not have
cold pressor D B P response. One study sampling (a novel experimental stressor in been potassium deficient or deficient
with only 20 subjects in each group de- the study of CVR in children) or as great enough for potassium supplementation to
tected a greater D B P response in black a BP response as cold pressor. This sug- have demonstrated attenuation of their
children by applying cold stimulus to the gests the possibility that video games do cardiovascular response. Even if the car-
face. 18 The difference in the technique of not induce as persistently robust a cardio- diovascular response to stress had been
cold stimulation in their study compared vascular response as do other stressors, enhanced by potassium deficiency, 1 week
with ours (face vs foot) may explain in and may therefore not be the best choice of potassium supplementation may not
part the larger racial difference in the of experimental stressor in the investiga- have been sufficient to demonstrate atten-
DBP response (14 mm Hg vs 3 mm Hg) tion of CVR in children. uation of that response. Although collec-
related to an overall greater D B P re- The cardiovascular responses in those tions of 12-hour overnight urine speci-
sponse in the black subjects (24 mm H g who received potassium supplementation mens before each study visit showed a

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THE JOURNAL OF PEDIATRICS SOROF ET AL.
Volume 13 I, Number I, Part I

significant increase in potassium excre- Racial contrasts in cardiovascular response H, Strong WB. Ethnic differences in the
t i o n - i n d i c a t i n g some degree of compli- tests for children from a total community. myocardial and vascular reactivity to stress
ance with the potassium supplement solu- Hypertension 1980;2:686-94. in normotensive girls. Am d Hypertens
8. Warren P, Fisehbein C. Identification of la- 1994;7:15-22.
t i o n - m a n y children complained of its bile hypertension in children of hyperten- 22. Wood DL, Sheps SG, Elveback LR,
unpleasant taste. As a result the overnight sive parents. Corm ivied 1980;44:77-9. Schirger A. Cold pressor test as a predictor
urine collections may not have reflected 9. Alpert BS, Dover EV, Booker DL, Martin of hypertension. Hypertension 1984;6:301-
the degree of compliance for the entire AM, Strong WB. Blood pressure response 6.
week, and children may have taken less to dynamic exercise in healthy children- 25. Menkes MS, Matthews KA, Krantz DS,
black vs white, d Pediatr 1981;99:556-60. Lundberg U, Mead LA, Qaqish B, et al.
than the prescribed amount of the potassi- 10. Takeshim A, Imaizumi T, Ashihara T, Cardiovascular reactivity to the cold pres-
um supplement solution. Yamamoto K, Hoka S, Nakamura M. sot test as a predictor of hypertension.
At this time it may be reasonable to rec- Limited maximal vasodilator capacity of Hypertension 1989;14:524-50.
o m m e n d that black children should in- forearm resistance vessels in normotensive 24. Murphy JK, Alpert BS, Walker SS, Wflley
young men with a familial predisposition to ES. Children's cardiovascular reactivity:
crease their intake of potassium-contain-
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