85

Atherosclerosis, 25 (1976) 85-94

@ Elsevier/North-Holland
Biomedical

Press, Amsterdam

MAXIMAL EXERCISE STRESS TESTING

HYPERLIPIDEMIC
CHILDREN

- Printed in The Netherlands

IN NORMAL

FREDERICK W. JAMES, CHARLES J. GLUECK, RONALD

FRANK MILLETT and SAMUEL KAPLAN

AND

W. FALLAT,

Department of Pediatrics (Cardiology), The Lipid Research Center of the Childrens

Hospital Medical Center and the General Clinical Research Center, College of Medicine,
University of Cincinnati, Cincinnati, Ohio (U.S.A.)
(Received 27th January, 1976)
(Revised received 12th April, 1976)
(Accepted 12th April, 1976)

summary
Electrocardiographic
and cardiovascular
responses during maximal exercise
were evaluated in 103 normal children and in 82 children with familial hyperlipoproteinemia.
The normal and hyperlipidemic
children were comparable in
regards to age, weight-height
index, resting and exercise blood pressures, and
maximal working capacity indices. The cohort of 82 hyperlipidemic
children
included 61 children (29 boys and 32 girls) with well defined monogenic
familial hyperlipoproteinemia.
Segmental ST depression on the exercise electrocardiogram
occurred in 8 of these 29 boys (27.6%) as compared to 4 of 55
normal boys (7.3%), P < 0.025 and in 6 of the 32 girls (19%) as compared to 7
of 48 normal girls (14.6%), P > 0.1. Segmental ST depression was present in
14 of 61 (23%) children with monogenic
hyperlipoproteinemia,
as compared
to 11 of 103 (10.75%) normals (x2 = 4.47, P< 0.05). An assessment of the
clinical significance of an abnormal exercise electrocardiogram
in male children
with monogenic
hyperlipoproteinemia
must await the following: (1) two to
four decades of observation and study of the development
of morbid or mortal
coronary disease, or (2) the future development
of improved invasive or noninvasive techniques for the early detection of covert coronary occlusive disease.
Currently,
maximal exercise electrocardiography
cannot be contemplated
as a
useful indicator of eventual premature coronary artery disease in asymptomatic
hyperlipidemic
children.
Supported in part by the American Heart Association, Southwestern Ohio Chapter Ad the General Clinical Research Center Grant No. RR-00068-13.
A portion of this work was done during Dr. Gluecks tenure
(1971-1976)
as an Established Investigator. American Heart Association.
Address for reprints: Frederick W. James. M.D., Division of Pediatric Cardiology, Childrens Hospital Medcal Center. Cincinnati, Ohio 45229, U.S.A.

86

Key words:

Children - Familial hypercholesterolemia

- ischemic heart disease - Maximal exercise electrocardiogmphy
-Premature
atherosclerosis

Introduction
Certain hyperlipoproteinemias
are closely associated with the development
of premature
ischemic heart disease (IHD) [l-3].
Adults, heterozygous
for
of IHD befamilial hypercholesterolemia
(FHC) may develop manifestations
fore age 30, but most commonly before age 50 to 60, and 50 to 70% of these
events are lethal [l-3].
FHC occurs in l/200 to l/600 unselected
American infants and is highly
penetrant
in the progeny of affected kindreds [4-71. Children heterozygous
for FHC do not have clinical signs of IHD [ 81, whereas, those with homozygous
FHC have angina, myocardial infarction (usually before age 20) and aortic ring
atheromata
[ 31. In autopsy studies in children and young adult males, there is
suggestive evidence that atherosclerotic
cardiovascular disease of the adult population may have its genesis during childhood
[g-11].
Exercise may induce
electrocardiographic
signs of myocardial ischemia in children with certain congenital heart diseases [ 12-141.
Since early demonstration
of myocardial
ischemia is of clinical significance in certain hyperlipoproteinemias,
we analyzed
the exercise electrocardiogram
to determine the prevalence of abnormal segmental ST depression in asymptomatic
hyperlipidemic
and normal children.
Materials and Methods
Eighty-two
children with well characterized
familial hyperlipoproteinemia
and 103 children with normal fasting cholesterol and triglyceride levels were
ascertained
by the Lipid Research Center during various lipid and lipoprotein
sampling studies [ 57,151. At least 2 fasting blood samples were obtained while
weights were stable on a habitual diet intake, and diagnoses of hyperlipidemia
were made following well characterized
analytical methods [ 21.
After measurement
of plasma lipids, we then established the following criteria for 2 study groups (normal and hyperlipidemic
children), in which all subjects had a normal resting physical examination
and electrocardiogram.
The
normal children also had normal fasting levels of cholesterol and triglyceride
and normal resting supine blood pressures as compared to values reported by
Londe [16], Masland et al. [17] and Heyden et al. [18]. Using these criteria,
103 subjects, 55 boys and 48 girls between the ages of 5 and 21 years were
classified as normal. The average age for both males and females was 13.
All hyperlipidemic children had primary elevation of cholesterol or triglyceride or both in 2 blood samples. To study as nearly a homogeneous
group of
children as possible, we established the following additional requirements
for
entry into the lipid study group: (a) Exclusion of secondary hyperlipidemia
[2,4,8].
(b) Documentation
of primary hyperlipidemia
in at least one additional first degree relative of the index child. (c) When possible, documentation
of monogenic
familial hypercholesterolemia
[7,8] by family studies which
revealed either 3 generation vertical transmission
or presence of tendon xan-

87

thomas or both (55 children, 23 kindreds). (d) Documentation

of monogenic
familial combined hyperlipidemia
[ 31 by 3 generation vertical transmission of
mixed II-A, II-B and IV lipoprotein
phenotypes
(4 children, 4 kindreds). (e)
Documentation
of monogenic
familial hypertriglyceridemia
[ 31 by 3 generation vertical transmission of Type IV lipoprotein
phenotypes
and endogenous
hypertriglyceridemia
(2 children, 2 kindreds).
Using these criteria, 82 children, 42 boys and 40 girls, between the ages of 5
and 21 years, had primary hyperlipoproteinemia
(Table 1). The average age of
the hyperlipidemic
males and females was 13. These 82 children came from 56
separate kindreds.
Exercise procedure
The 103 normolipidemic
children and the 82 hyperlipidemic
children underwent a continuous
graded maximal bicycle exercise test. The exercise test was
performed on a Quinton Instrument
Ergometer (Model 844). Each subject was
tested in 1 of 3 exercise programs which were based on body surface area
(BSA). The limits of BSA for each program were as follows: <l M* (Program I),
l-1.19
M* (Program II) and 21.2 M* (Program III) [14].
A 12-lead electrocardiogram
and Frank orthogonal
leads (X,Y,Z) were recorded in the supine and standing positions with and without hyperventilation.
During exercise each subject was urged to continue until his maximum voluntary exercise capacity was reached. That level of exercise was considered the
end point for calculating the maximal working capacity. Blood pressure was
measured every 2-3 min. Precordial leads Vl, V5 and V6 and Frank orthogonal leads X,Y,Z [19] were simultaneously
recorded every minute. Additional
details of the exercise method have been described elsewhere [ 141.
Data analyses
The exercise data were interpreted
by the cardiologists
who had no foreknowledge of the cholesterol and triglyceride levels or the family study results
in the children. Weight+eight
index (body weight (kg)/body height (m)) was
used as a measurement
of body size [ 14,201.
The maximal blood pressure and heart rate were recorded when the maximal
voluntary
capacity level was reached. The maximal working capacity was calculated from the work loads (kg-m/min) and the exercise time (min). The maximal working capacity index (MWCI) was calculated as a ratio between the
maximal working capacity and body weight (in kg) or BSA (in m*).
Seven leads (2,3,AVF,V5,V6,X
and Y) were analyzed on the exercise electrocardiogram
(E-ECG) for segmental ST depression.
Five consecutive
complexes in the previous minute prior to the patients maximal voluntary capacity
were measured and averaged. The criterion for a positive E-ECG was segmental
ST depression 21 mm [21] extending for at least 0.06 set after the J point
[ 221 below the p-q segment level combined with a horizontal [ 211, downward
sloping [ 211, or upward sloping [ 21,23-251
ST segment contour.
Besults
Normal and hyperlipidemic children
Lipid levels
The distributions
for cholesterol and triglyceride

levels for the children

with

50

18

50

42

29

18

37

17

237

220

245

134

224

115

80

62

80

58

275

148

275

164

50th

AND

133

86

110

85

288

172

320

177

75th

TRIGLYCERIDE

170

120

166

102

336

198

363

199

90th

IN NORMAL

9 5th

208

128

188

123

358

204

389

360

137

254

132

363

214

420

213

99th

HYPERLIPIDEMIC

211

AND

42

55

40

48

36 a

55

38

48

CHILDREN

99f

68+-

89+-

62+-

274 +

156*

291 c

167+

F+

10d

gd

9 c

SE

aExcludes 2 females with primary hyperlipidemia

who had normal cholesterol (160, 170 mg/lOO ml) but elevated triglyceride levels (254, 220 mg/lOO ml).
bExcludes 6 mates with primary hyperlipidemia
who had normal cholesterol (168. 178, 180, 200. 209. 215 mg/lOO ml) but elevated triglyceride levels (146.162.
164.170, 178, 248 mg/lOO ml).
CP < 0.001, cholesterol levels in hyperlipidemic
females vs. normal females. hyperlipidemic
males. vs. normal males.
dP < 0.02. triglyceride levels in hyperlipidemic
females vs. normal females, hyperlipidemic
males vs. normal males.
a = Mean; +SE = standard error.

Normal males
Hyperlipidemic
males

Triglyceride
Normal females
Hyperlipidemic
females

Normal males
Hyperlipidemic
males e

145

124

6th

25th

OF CHOLESTEROL

Percentile

DISTRIBUTION

Cholesterol
Normal females
Hyperlipidemic
females

PERCENTILE

TABLE

89

primary hyperlipidemia
and for normals are summarized in Table 1. Of the 82
children with primary hyperlipidemia,
74 had predominant
hypercholesterolemia, with essentially no overlap in the disparate distributions
of cholesterol
levels in affected and normal children. Since 8 of 82 children with primary hyperlipidemia
had predominant
hypertriglyceridemia,
the distribution
of triglycerides for normal and hyperlipidemic
children has considerable overlap, although there were notable distinctions in group means which were higher for
P < 0.02 (by Students t-test). Fiftyboth boys and girls with hyperlipidemia,
five of the 82 hyperlipidemic
children came from kindreds thought to have
monogenic
familial hypercholesterolemia,
4 from kindreds with familial
combined hyperlipidemia,
and 2 from kindreds with familial hypertriglyceridemia.
Age, weight-height index, blood pressure and maximal working capacity
The normal
and hyperlipidemic
groups were further
subdivided
by
sex (Table 2). Comparing the males to males and females to females from both
groups, there were no significant differences
in the mean ages and weightheight indices. Also, the resting blood pressures and maximal systolic blood
pressures were not different in either group except for the maximal diastolic
blood pressure being significantly
higher in the hyperlipidemic
males than in
the normal males.
There were no significant differences in the mean exercise times and maximal

TABLE 2
THE MEAN AGES, WEIGHT-HEIGHT
PERLIPIDEMIC CHILDREN

INDICES,

AND BLOOD

PRESSURES

IN NORMAL

AND HY-

Age

W-HI

RSBP

RDBP

MSBP

MDBP

77
16.1
2.2
83.2 a
12.4
1.9

(Yrs)

M&S
Normal

55

HyperIipidemic

42

8
+SD
+SE
8
+SD
+SE

13.1
4
0.5
13.1
4
0.6

30.9
8.1
1.1
30.3
8.1
1.3

112.8
11.9
1.6
116.1
14.6
2.2

71.2
10.4
1.4
73.5
9.5
1.5

167.7
33.6

8
+SD
*SE
a
*SD
*SE

13
4.2
0.6
13.2
4
0.6

30.2
11.3
1.7
31.9
11.6
1.8

112.6
11.9
1.7
117.3
13.4
2.1

72.2
10.1
1.5
73.4
10
1.6

153.2
27.2
4
162.2

4.5
174.8
33.1
5.1

Femde.S

Normal

48

Hyperlipidemic

40

25.2
4

N = number of children
W-HI = weight-height index
RSBP = resting syst.oIic blood pressure
RDBP = resting diastolic blood pressure
MSBP = systolic blood pressure at maximal exercise
MDBP = diastolic blood pressure at maximal exercise
SD = standard deviation, SE = standard error. x = mean.
a The MDBP is higher in the hyperlipidemic males than in the normal maks, P < 0.05.
Other comparisons within the sex groups were not significantly different, P > 0.1.

82.8
9.4
1.4
83.8
11.1
1.8

90

TABLE

THE MEAN

EXERCISE

HYPERLIPIDEMIC

TIMES

AND

MAXIMAL

WORKING

CAPACITY

INDICES

IN NORMAL

AND

CHILDREN
N

ET

MWC/M2

MWC/kg

x
+SE
s
tSE

12.2
0.7
11.15
0.6

5146
414
4316.2
334

160
13.5
128.4
6.4

x
+SE
K
*SE

9.02
0.49
9.2
0.5

M&S

Normal

55

Hyperlipidemic

42

Fe?tlde.S

Normal

46

Hyperlipidemic

40

3240
211
3111
204

99.9
1.4
97.3
6

Within the sex groups compared variables were not significantly different, P > 0.1.
N = number, ET = exercise time, MWC/m2 or /kg = maximal working capacity per body surface area (m2)
or body weight (kg).

working capacity indices (MW&) in the comparison of males to males and females to females from each group (Table 3). However, the mean MWCI were
higher in the males than in the females.
Exercise electrocardiograms
Normal children
ST depression was not present in any child before exercise. During exercise,
ST depression > 1 mm was recorded in 4 boys and 7 girls (Table 4). No arrhythmias were recorded.
TABLE

A COMPARISON
NORMAL

OF SEGMENTAL

AND HYPERLIPIDEMIC
ST Depr

ST DEPRESSION

> 1 mm DURING

No ST Depr

x2

Males

Hyperlipidemic
Normal

MAXIMAL

EXERCISE

IN

CHILDREN
ST Depr

No ST Depr

x2

Females

9
4

33
51

4.12a

6
7

34
41

0.003NS

8
4

21
51

6.4 b

6
7

26
41

0.25NS

Monogenic
hyperlipidemia
Normal

Males and

females

Hyperlipidemic
Normal

15
11

61
92

2.2NS

Monogenic
hyperlipidemia
Normals

14
11

41
92

4.47 a

Monogenlc = hyperlipoproteinemia
with vertical transmission in 3 generations, or in 2 generations in
kindreds with familial hypercholesterolemia
and tendon xanthomas in adult subject. Of 82 children with
primary hyperlipidemia,
61 were shown to have monogenic
hyperlipidemia.
Depr = depression, NS = not significant, x2 = Chi-square.
a P < 0.05.
b P < 0.025.

91

Hyperlipidemic children
In order to focus on those children with the best defined, and generally quantitative most severe primary hyperlipidemia,
studies of the frequency of ST depression were made in the 61 children with well defined monogenic
familial
hyperlipoproteinemia
(Table 4). Segmental ST depression was present in 8 of
29 hyperlipidemic
boys (27.6%), which was 3 times more frequent than in normal boys, 4 of 55 (7.3%), P < 0.025 by CHI square analysis (Table 4). Segmental ST depression was present in 6 of 32 (19%) girls with monogenic
familial
hyperlipoproteinemia,
but this was not more frequent than in normal girls (7/
48, 14.6%), P > 0.1. When all children with monogenic hyperlipoproteinemia
were considered together, and compared to all normal children, ST depression
was more common in hyperlipidemic
children (Table 4).
Discussion
Our study revealed that abnormal ST depression was more prevalent in boys
with monogenic
hyperlipoproteinemia
than in normolipemic
boys. At the
present time, we are unable to interpret the significance of our findings of abnormal ST depression in 7.3% of the normal males and 14.6% of normal females. There is, however, a parallel finding of a high incidence of false positives in normal adult females [26-281
as compared to normal adult males.
The results of the exercise electrocardiogram
are reproducible,
since each of 20
hyperlipidemic
and 31 normolipemic
children has demonstrated
identical ST
segment changes on both, the initial and follow up, exercise tests.
A preliminary analysis of post-exercise
systolic time intervals in these same
children has revealed that the duration of the pre-ejection period and the ratio
of pre-ejection
time:left ventricular
ejection time were significantly increased
in the hyperlipidemic
boys as compared to the normolipidemic
boys, P < 0.05.
[29] In the girls, the post-exercise
systolic time intervals were similar in both
patient and control groups. In the presence of a relatively large group of presumably false positive exercise tests in normal children it is difficult to make
firm conclusions
regarding the significantly
increased incidence of abnormal
tests in hyperlipidemic
boys.
We could not contemplate
coronary arteriography
to diagnose coronary occlusive disease in asymptomatic
children who have an abnormal maximal exercise test and familial hyperlipoproteinemia,
particularly
since similar studies
would also have to be done in normal controls for comparison. There are then
no immediate prospects to obtain direct objective visualization of the coronary
arteries in these children. Follow-up studies to provide evidence to link the
ECG changes with the clinical development
of morbid or mortal premature
coronary disease will require at least 2-5 decades in this group of children. The
significance of an abnormal exercise electrocardiogram
in these patients will
then have to await further clinical follow-up studies accompanied hopefully in
the future by sophisticated non-invasive or improved invasive techniques for detecting and measuring coronary artery occlusion.
Several investigative groups have analyzed the exercise electrocardiogram
in
asymptomatic
children between the ages of 5 and 21 years. Goldberg [30] recorded segmental ST depression of l-2 mm during exercise in 5% of normal

children, using single lead (CR6) electrocardiography.

Bengtsson [ 311 analyzed
the exercise electrocardiogram
using multiple leads in 99 asymptomatic
children
between the ages of 5 and 21 years. During tachycardia,
the ST segment position was measured at 50 msec or less after the J point. The exact percentage of
patients with ST depression at maximal exercise is difficult to determine from
this series. However, ST depression of l-l.5
mm was recorded in a few subjects during and after exercise. SjSstrand [ 321 studied the relationship between
the ST segment level on the electrocardiogram
and heart rate in 70 adult men
and women during the administration
of pharmacological
agents and exercise.
The ST segment level was measured in relationship to the p-q level at 20 msec
after the J point. ST depression of 1 mm was recorded in more than one electrocardiographic
lead during exercise. This author suggested that the shift in the
ST level was due to a slow change of potential after the T wave which produced
an elevation in the p-q level as diastole was shortened. As a result, the ST segment appears to be depressed.
Our study differs from the above series in that we recorded the exercise electrocardiogram
using multiple conventional
and the Frank orthogonal lead systems. Our method of analyzing the ST segment and the interpretation
of a positive change on the exercise electrocardiogram
were different. Also, our data
was segregated according to lipid levels and sex. Because of these differences, it
is difficult to compare our study with the findings of Goldberg [ 301, Bengtsson
[31] or Sjiistrand [32].
Rogers et al. [33] analyzed the E-ECG for J point displacement and ST segment slope in 73 asymptomatic
adolescent males. J point or segmental ST depression alone or in combination
was not recorded in any of their patients. The
authors suggested that any J point depression on the E-ECG should be considered abnormal in the adolescent male. J point depression < 1.5 mm with an
upward sloping ST segment did occur in many of our patients. However, J point
depression combined with depression of the ST segment for 60 msec or more
below the isoelectric line was more than we expected from tachycardia
alone
and was considered a positive finding in these children.
In adults, segmental ST depression on the E-ECG has been observed in patients with hypertension,
obesity and abnormal blood lipids [21]. Moreover,
several studies [34-361
have suggested that an abnormal maximal treadmill
test (MTT) response in adults has significant predictive value for subsequent development of clinical coronary disease and might be considered as an independent risk factor. Froelicher et al. [34] observed that adults with ischemic ST
segments provoked by dynamic exercise have an increased risk of developing
subsequent covert coronary heart disease [34]. Bruce et al. [35] reported that
clinical coronary artery disease developed over a 5-year interval in 3 of 22 normal subjects (13.6%) who initially had an abnormal MTT. In 199 normal subjects who initially had a normal MTT, 2 (1%) developed clinical signs of coronary artery disease over the same 5 year interval. Aronow [36] reported the development of clinical coronary artery disease over a 30 months interval in 3 of
13 normal subjects with an initially abnormal MTI. In 87 normal subjects with
an initially normal MTT, 1 (1.1%) developed clinical coronary artery disease
during the same 30 month interval.
Carlson et al. [37] observed an increased frequency of abnormal ST depres-

93

sion in asymptomatic
adults with primary hyperlipidemia
and suggested that
the increased frequency of the ST depression was positively related to the concentration of both low density and very low density lipoproteins.
However, the limitations
of exercise electrocardiography
in hyperlipidemic
adults have recently been demonstrated
by Borer et al. [ 381. In hypercholesterolemic subjects who had an abnormal exercise test in the absence of other indications of coronary artery disease, only 37% had greater than 50% stenosis,
30% had less than 5096, and 33% had normal coronary arteries. Borer et al. concluded that . . . the diagnostic usefulness of exercise electrocardiography
is
limited. False-negative
responses are frequent in patients with clinically suspected coronary disease, and false-positive responses frequent in asymptomatic
patients [ 381. Hence, even in adults where occlusive coronary artery disease is
presumably
well developed, the significance of abnormal electrocardiographic
response is difficult to evaluate. Any attempt at this time to interpret the abnormal maximal exercise ECG as predictive for premature coronary artery disease in high risk children with monogenic
hyperlipidemia
would be purely
speculative. Maximal exercise electrocardiography
in children with familial hypercholesterolemia
can be viewed as an experimental
attempt to provide early
information
relative to coronary artery disease which can only be validated by
long term follow-up for several decades or the development
of improved invasive or non-invasive methods for providing objective evidence of occlusive coronary artery disease. Hence, conventional
maximal exercise electrocardiography
in asymptomatic
children with monogenic
familial hypercholesterolemia
cannot then be contemplated
as useful in the routine clinical evaluation of this disorder which is associated with a high risk of premature coronary artery disease.
Acknowledgements
We thank Mrs. Vera Naylor, Miss Mary Jo Sandker and Mrs. Anne Doerner
for their technical assistance; and Mrs. Margaret DeHo for typing the manuscript.
References
1 Stone. N.J.. Levy, RI.. Fredrickson, D.S. and Verter. J., Coronary artery disease in 116 kindred with
familial type II hyperlipoproteinemia, Circulation, 49 (1974) 476.
2 Fredrickson. D.S. and Levy. RI.. Familial hyperlipoproteinemia. In: J.B. Stanbury, J.B. Wyngaarden
and D.S. Fredrickson (Eds.). The Metabolic Basis of Inherited Disease, McGraw-Hill, New York, N.Y.,
1972, p. 545.
3 Goldstein, J.L.. Schrott, H.R.. Hazzard, W.R.. Bierman, E.L. and Motulsky. A.G.. Hyperlipidemia in
coronary heart disease, Part 2 (Genetic analysis of lipid levels in 176 families and delineation of a
new inherited disorder, combined hyperlipidemia). J. Clin. Invest., 52 (1973) 1544.
4 Glueck. C.J.. Fallat. R.W. and Tsang. R.C., Hypercholesterolemia and hypertrlglyceridemia in children
- Pediatric approach to primary atherosclerosis prevention, Amer. J. Dis. Child.. 128 (1974) 569.
5 Tsang. R.C.. Fallat. R.W. and Glueck. C.J., Cholesterol at birth and age, Part 1 (Comparison of normal
and hypercholesterolemic neonates), Pediatrics. 53 (1974) 458.
6 Goldstein, J.L., Albers, J.J.. Schrott, H.G.. Hazzard, W.R., Bierman, E.L. and Motulsky. A.G., Plasma
lipids levels and coronary heart disease in adult relatives of newborns with normal and elevated cord
blood lipids, Amer. J. Hum. Genet., 26 (1974) 727.
7 Tsang. R.C., Glueck. C.J., Fallat. R.W. and Mellies. M.. Neonatal familial hypercholesterolemia,
Amer. J. Dis. Child., 129 (1975) 83.
8 Kwiterovich. P.O.. Levy, R.I. and Fredrickson, D.S.. Neonatal diagnosis of familial type II hyperlipoproteinemia, Lancet, 1 (1973) 118.

94

9 Strong, J.P.
(1969)
251.

and McGill.

Jr.,

H.C..

The pediatric

aspects

of atherosclerosis,

Pesonen. E., Norio. R. and Sama. S.. Thickenings in the coronary

of genetic factors in coronary heart disease, Circulation,
51 (1975)

11

McNamara.
J.J.. Molot. M.A.. Stremple,
J.F. and Cutting, A.T., Coronary
artery disease in combat
casualties in Vietnam, J. Amer. Med. Ass., 216 (1971)
1185.
Hzdioren, K.H., The telemetered
exercise electrocardiogram
in congenital aortic stenosis, Pediatrics,
47 (1971)
31.
James, F.W., Effects of physical stress on adolescents
with normal or abnormal cardiovascular
function, Postgrad. Med., 56 (1974)
53.
James, F.W. and Ka~ian. S., ST depression and systolic hypertension
during exercise in aortic insufficiency, Circulation.
50 (1974)
U-27.

13
14
15
16
17
18

19
20
21

22
23
24
25
26
27

28
29
30
31
32
33
34

35
36
37
38

in infancy

Res..

10

12

arteries
218.

J. Atheroscler.

as an indication

Glueck. C.J., FaIIat. R.W., Tsar&. R.C. and Buncher. CR., Hyperhpidemia
in progeny of parents with
myocardiai
infarction before age 50, Am. J. Dis. Child.. 127 (1974)
70.
Londe, S., Blood pressure in children as determined under office conditions.
Clin. Pediatrics, 5 (1975)
71.
MasIand. Jr., R.P., HeaId. F.P., Goodaie, W.T. and Gallagher, J.R.. Hypertensive
vascular disease in
adolescence,
New EngI. J. Med., 255 (1956)
894.
Heyden. S., Bartel, A.G.. Hames. C.G. and McDonough.
J.R., Elevated blood pressure levels in adolescents. Evans County, Georgia - Seven-year follow-up of 30 patients and 30 controls, J. Amer. Med.
Ass., 209 (1969)
1683
Blomqvist,
C.G.. Use of exercise testing for diagnostic and functional evaluation of patients with arteriosclerotic
heart disease, Circulation 44 (1971)
1120.
Sive, P.H.. Medaiie. J.H., Kahn, H.A.. Neufeld, H.N. and Riu, E., Correlation
of weight--height
index
with diastolic and with systolic blood pressure, Brit. J. Prev. Sot. Med., 24 (1970)
201.
Blackburn,
H., The exercise
electrocardiogram,
technological
procedural
and conceptual
developments. In: H. Blackbum (Ed.), Measurement in Exercise Electrocardiogram,
Charles C. Thomas, Springfield, Iii.. 1969, p. 220.
Linhart, J.W. and Turnoff,
H.B., Maximum
treadmill exercise test in patients with abnormal control electrocardiogram,
Circulation. 49 (1974)
667.
Kattus. A.A.. Exercise electrocardiography
-Recognition
of the ischemic response, false positive and
negative patterns. Amer. J. Cardiol., 33 (1974)
721.
Case. R.B.. Nasser, M.G. and Crampton. R.S., Biochemical
aspects of early myocardiai &hernia.
Amer.
J. Cardiol.. 24 (1969)
766.
Stuart, Jr., R.J. and Eiiestad, M.H., Upsloping S-T segments in stress testing-a six-year follow-up Correlation in 248 angiograms (Abstr.), Circulation,
50 (1974)
111-8.
Astrand,
I., Exercise electrocardiograms
recorded
twice with an 8-year interval in a group of 204
women and men 4843
years old, Acta Med. Scand., 178 (1965)
27.
Lepeschkin.
E., Physiological
factors influencing the electrocardiographic
response to exercise. In: H.
Blackburn
(Ed.), Measurement
in Exercise Electrocardiography,
Charles C. Thomas, Springfield, III.,
1969, p. 363.
Gumming. G.R.. Dufresne, C.. Kich, L. and Samm. J.. Exercise electrocardiogram
patterns in normal
women, Brit. Heart J.. 35 (1973)
1055.
James, F.W.. Glueck. C.J.. Kaplan, S. and Naylor. V., Exercise electrocardiogram
and postexercise
systolic time intervals in hyperiipidemic
children. Ciin. Res.. 23 (1975)
471A.
Goldberg, S.J.. Exercise in cardiac patients. In: A.J. Moss and F.H. Adams (Eds.). Heart Disease in Infants, Children. and Adolescents,
Wiiams
and Wilkins. Baltimore,
Md., 1968, p. 270.
Bengtsson.
E.. The exercise electrocardiogram
in healthy children and in comparison
with adults. Acta
Med. Scand., 154 (1956)
225.
Sjiistrand. T.. The relationship between the heart frequency and the ST level of the e1ectrocaxliogra.m.
Acta Med. Scand.. 138 (1950)
201.
Rogers, J.H., Strong, W.B. and HeRerstein. H.K.. The exercise electrocardiogram
in trained and untrained adolescent males (Abstr.), Pediatric Res.. 9 (1975)
270.
Froehcher.
Jr., V.F.. Thomas, M.N., Pillow. C. and Lancaster,
M.C., Epidemiologic
study of asymptomatic men screened by maximal treadmill testing for latent coronary
artery disease, Amer. J. Cardiol.. 34 (1974)
770.
Bruce, R.A. and McDonough. J.R.. Stress testing in screening for cardiovascular
disease, Bull. N.Y.
Acad. Med., 45 (1969)
1288.
Aronow,
W.S., Thirty-month
follow-up of maximal treadmill stress test and double masters test in
normal subjects. Circulation, 47 (1973) 287.
Carlson. L.A.. Ekelund,
L.G. and Olsson, A.G.. Frequency of ischemic exercise ECG changes in
symptom-free men with various forms of primary hyperlipidemia, Lancet, 2 (1975) 1.
Borer. J.S., Brensike, J.F., Redwood, D.R.. Itscoitz, S.D.. Passman, E.R., Stone, N.J.. Richardson,
J.M.. Levy. R.I. and Epstein, S.E., ECG response to exercise in predicting coronary-artery
disease,
New En%. J. Med., 293 (1975)
367.