VOLUME 78. AUGUST 1986. NUMBER 2
Pediatrics
Serum
Apolipoproteins
A-I and
B in 2,854
Children
From
a Biracial
Community:
Bogalusa
Heart
Study
Sathanur R. Srinivasan, PhD, David
S. Freedman,
PhD,
Chakravarthi Sharma, PhD, Larry S. Webber, PhD, and
Gerald
S. Berenson,
MD
From the Departments of Medicine, Biochemistry, Public Health and Preventive Medicine, and Biometry and Genetics, Louisiana State University Medical Center, New Orleans
ABSTRACT. Serum apolipoprotein A-I (apo A-I) and
apolipoprotein B (apo B) profiles were examined in 2,854
children, 5 to 17 years of age, from a total biracial
community. Black boys had higher apo A-I levels than white boys (P < .001), whereas girls showed no such
race-related difference. Black-white difference in apo A-I
per-sisted among boys with similar triglyceride levels
pro-vided that triglyceride levels were high. The ratio of
high-density lipoprotein cholesterol (HDL-C)/apo A-I was higher in black than in white children, irrespective of sex
(P < .001). Only black children showed sex-related
dif-ferences for apo A-I (boys > girls, P < .05). Sex-related differences were seen in white children for HDL-C/apo
A-I ratio (boys > girls, P < .001) and in children of both
races for apoB (girls > boys, P < .01). Age-related changes
were more apparent for apo A-I and HDL-C/apo A-I
ratio than for apo B. A progressive decrease in apo A-I
was noted during sexual maturation only in white boys.
The magnitude of inverse association of apo B to
HDL-C was less strong in black children (P < .01). Although apo A-I was inversely correlated with very low-density lipoprotein cholesterol and triglycerides in white
chil-dren, no association was noted in black children. These
findings are indicative of intrinsic metabolic differences
among the race-sex groups, resulting in variability in
lipoprotein composition and levels and atherogenic
po-tential. Pediatrics 1986;78: 189-200; apolipoprotein A-I, apolipoprotein B.
Received for publication May 28, 1985; accepted Nov 21, 1985. Reprint requests to (G.S.B.) Department of Medicine, LSU Medical Center, 1542 Tulane Aye, New Orleans, LA 70112.
PEDIATRICS (ISSN 0031 4005). Copyright © 1986 by the
American Academy of Pediatrics.
The pathologic precursors of coronary heart
dis-ease are now recognized as originating in
child-hood.’3 Serum lipoproteins are considered
impor-tant risk factor variables in this regard, with
low-density lipoproteins (LDL) and high-density
lipo-proteins (HDL) showing positive and inverse risk
associations, respectively.47 Consequently, there
has been a surge of interest in studying the
evolu-tion of serum lipoprotein profiles in children.
Recently, serum lipid and lipoprotein
distribu-tions in US children from major population-based
studies have been reported.81’ Of these, the
Boga-lusa Heart Study provides lipoprotein profiles of a
biracial (black-white) pediatric population. Our
studies show that the most dramatic changes in
serum lipids and lipoproteins occur during the first
year of life, with the mean level of total cholesterol
essentially approaching the young adult level by 1
to 2 years of age.12”3 Age- and sex-related
differ-ences in lipoproteins differ markedly from adult
patterns. Lipoprotein transitions occur during
sex-ual maturation so that adult patterns of elevated
levels ofboth very low-density lipoproteins (VLDL)
and LDL and decreased levels of HDL in males v
females are reached.14”5 In addition, consistent
race-related differences exist in children for VLDL
(whites > blacks) and
HDL
(blacks
> whites).9”6The above lipoprotein changes are measured in
and HDL-C), one of several components of lipopro-teins.
Serum lipid classes are bound in a spectrum of
proteins called apolipoproteins, which are an
inte-gral part of lipid transport. Among the known
apo-lipoproteins (apo), B and A-I are of particular
in-terest. Apo B is the predominant protein
constitu-ent of VLDL and LDL and serves as the principal
carrier of lipids to peripheral tissues.’7 On the other
hand, apo A-I is found as the major apolipoprotein
of HDL particles and functions as an activator of
lecithin-cholesterol acyltransferase, a key enzyme
in the reverse transport of cholesterol from the
peripheral tissues.’8”9
Studies in adults suggest that apolipoproteins
may serve as better predictors of coronary heart
disease than lipoprotein cholesterol.20’2’ To date,
there are only a few studies describing
apolipopro-tein levels in the general adult population.2224 The
present study describes the apo A-I and apo B
profiles in 5- to 17-year-old children from a biracial
community.
MATERIALS
AND
METHODS
Population
In 1981 to 1982, 3,314 five- to 17-year-old
school-children residing in Bogalusa, LA, were examined,
representing 80.2% of all eligible individuals. With
this participation rate it is reasonable to conclude
that the sample was representative of the target
population. Observations from a substudy of 761
nonparticipants revealed that less than 6% of older
nonparticipants refused because of “medical
prob-lems,” and more than 30% of these individuals
expressed outright refusal without giving specific
reasons.25
Analyses involving apo A-i and apo B
measure-ment were restricted to children fasting for 12 hours
prior to examination (n = 2,923), and compliance
was determined by interview on the morning of
examination. Apo A-I and apo B determinations
were not available for 2.4% (n = 69) of the fasting
children. Of those with apolipoprotein
measure-ments, 926 (32%) were white males, 907 (32%) were
white females, 478 (17%) were black males, and 543
(19%) were black females.
Physical
Examination
A physical examination was given by a physician,
and sexual maturation was determined by visual
assessment of secondary sex characteristics
accord-ing to the method of Tanner.26 The ratings for
sexual maturation ranged from 1 (no development)
to 5 (complete development) according to the stages
of female breast or male genitalia development.
Collection
of Blood
Specimens
Antecubital venous blood was collected in
Vacu-tamer tubes and allowed to clot for approximately
i#{189}hours. After centrifugation, sera were collected
in tubes containing thimerosal (Aldrich Chemical
Co, Milwaukee, WI) and sent in a cold-packed box,
by bus, to the New Orleans Core Lipid Laboratory
of the National Research and Demonstration
Cen-ter-Arterioscierosis where it was kept at 4#{176}C.The
following day the sera were analyzed for lipids,
lipoproteins, and apo B, and the remaining samples
were kept frozen at -20#{176}Cuntil apo A-I
measure-ments were made (the samples remained stored 9
to 15 months).
A second independent blind duplicate blood
sam-pie was collected at each screening day on a 10%
random subsample of the children to estimate
mea-surement errors.
Serum
Lipid and Lipoprotein CholesterolAnalyses
Cholesterol and triglyceride contents of whole
serum were determined in a Technicon
Auto-Analyzer II according to the laboratory manual of
the Lipid Research Clinics Program.27 The
labora-tory has been designated as standardized by the
Centers for Disease Control in Atlanta. An
isopro-panol extract of the sample was used for the
deter-minations. A serum calibrator, provided by the
Centers for Disease Control, was used to convert
the cholesterol values obtained by the
Auto-Analyzer II to the reference method of Abell et al.28
Serum VLDL-C, LDL-C, and HDL-C were
mea-sured by a combination of heparin-calcium
precip-itation and agar-agarose gel electrophoresis
proce-dures. A detailed description of this method,
in-cluding measurement errors and its application in
the Bogaiusa Heart Study, has been reported.9 The
specificity and quantitative aspects of the method
for the precipitation of apo B-containing
lipopro-teins have been well documented.29’3#{176}
Apolipoprotein
Assay
The levels of apo B and apo A-I in whole serum
were assayed by the electroimmunoassay procedure
of Laurell.3’ Antibodies to LDL (density 1.03 to
1.05 g/mL) and apo A-I (prepared by the procedure
of Miller et a132) raised in goats were used. The
electroimmunoassay for apo B was performed with
the use of antibody in 1.2% (w/v) agarose gel,
Tris-tricine buffer pH 8.6 at 6 V/cm for five hours. No pretreatment of samples and standards was carried out. In contrast, conditions for apo A-I were altered:
Electrophoresis was performed in 1.8% (w/v)
TABLE 1. Measuremen Determinations: Bogalusa
t Error for Serum Apolipoprotein B and Apolipoprotein A-I
Heart Study
Variable No. of
(Blind)
Mean (mg/dL) Measurement Error
SD Coefficient of
Variation
(%)
Sample 1 Sample 2
Apolipoprotein B 319 86.3 86.4 4.6 5.4
Apolipoprotein A-I 319 141.4 141.0 8.8 6.3
of samples, and standards were treated with 8 M
urea and 1% Nonidet P-40 detergent (final
concen-tration).33 Frozen aliquots from a pooled serum, in
which apo B and apo A-I were determined, served
as secondary standards.
Intraassay and interassay coefficients of
varia-tion ranged, respectively, 2.3% to 4.i% and 1.6% to
4.4% for apo B v 0% to 5.2% and 2.3% to 6.0% for
apo A-I. Measurement errors from the ‘blind
dupli-cate samples are given in Table 1. Because two
independent samples were collected from each of
319 individuals, the measurement error includes
errors associated with collection, processing, and
analysis of the samples, as well as with data
proc-essing. In addition to these quality control
meas-ures, the laboratory is participating in the
apolipo-proteins A-I and B standardization program of the
International Union of Immunological Societies,
Centers for Disease Control, and National Heart,
Lung, and Blood Institute.
No efforts were made to determine any possible
effect of frozen sample on apo A-I measurements.
Earlier studies have used frozen samples for
apoli-poprotein analysis.2224 Recently, Blum34 reported
that when samples were stored at -20#{176}Cas long as
8 years, there was no apparent relationship between
storage time and the values obtained for apo A-I.
Statistical Analysis
Because race and sex interactions were present,
ttests were performed within strata defined by race
or sex. Polynomial regression (using age, age2, and
age3 as independent variables) within each race-sex
group indicated three age groups differing according
to apolipoprotein changes. Piecewise regression
techniques35 were then used to calculate yearly
changes in predicted apolipoprotein levels within
each age group.
Differences in the magnitude of the Pearson
cor-relation coefficients were assessed after applying
Fisher Z transformation and assuming a variance
of i/(n -‘ 3)36 Race-, sex-, and age-specific Z scores
(relative deviates) for apo A-I and triglycerides were
calculated.’#{176} These standardized values were used
to assess the relationship between apo A-I and
triglycerides in each race-sex group, independently
of age. The possibility that race-related differences
in triglyceride and apo A-I levels could account for
apo A-I and triglyceride differences, respectively,
between the races was examined by matching age
and apo A-I or triglyceride levels. (Analysis of
co-variance was considered inappropriate because the
relationship between apo A-I and triglycerides
dif-fered between the races.)
RESULTS
Distributions and Mean Levels by Race and Sex
Distributions, mean levels, and both race- and
sex-related differences of the major serum lipids
and lipoprotein cholesterols remained essentially
the same as previously reported9”4 (data not
shown). Race- and sex-specific distributions of apo
A-I and apo B are shown in Figs 1 and 2; the mean
values of the apolipoproteins, along with HDL-C
and HDL-C/apo A-I ratio, are given in Table 2.
Because apo B is derived from both VLDL and
LDL, no ratio relating apo B to either of these
lipoprotein cholesterols was determined.
The distributions of apo A-I and apo B were
unimodal with median values almost identical with
the means. However, distributions of both
apoli-poproteins were skewed to the right, especially apo
B. Overall, levels of HDL-C and HDL-C/apo A-I
ratio were significantly higher in black children
than in white children, irrespective of sex. However,
apo A-I was significantly higher in blacks than in
whites only among boys. No race-related
differ-ences were noted for apo B. With respect to
sex-related differences, levels of HDL-C and HDL-C/
apo A-I ratio were significantly higher in white boys
than in white girls. In contrast, only black children
showed such significant sex-related differences for
apo A-I, with black boys showing higher values
than black girls. In both races, apo B was
signifi-cantly higher in girls than in boys.
Effect of Age
Race-, sex-, and age-specific mean levels of apo
A-I and apo B are shown in Fig 3. Age-related
changes were more apparent for apo A-I than for
apo B among all the four race-sex groups. For
o---o boys, N926 .‘-.. girls, N=907
o---o boys, N478 .-. girls, N543
Boys Girls
o---o whit#{149},N=926
.-. black, N=475
o---o whits, NSO7 S.-. black, N=543
140 180 220 0 60 100 140 180 220
Apo A-I, mg/di
50
WhIt#{149} Black
U
C
.
3
U.
40’
30’
20’
10
0-a
40 ‘ 80 #{149}120 ‘ 160 ‘ 200 0 40 80 120 160 200Apo B, mg/dl
Fig 1. Distributions ofserum apolipoprotein (apo) A-I in boys and girls by race: Bogalusa Heart Study.
‘S
U C
3
U.
30
20
1
0-0 60 100
Fig 2. Distributions of serum apolipoprotein (apo) B in white and black children by sex:
Bogalusa Heart Study.
TABLE 2. Serum Levels
(HDL-C), and High-Density
of Apolipoprotein (Apo) A-I
Lipoprotein Cholesterol to A
, Apolipoprotein B, High-Density Lipoprotein Cholesterol polipoprotein A-I Ratio by Race and Sex*
Apo A-I (mg/dL)
Boys
-
-
.
-______--White Black
(n = 926) (n = 478)
139 ± 21 144 ± 21
Girls Race
Differences
White Black (P.<)
(n = 907) (n = 543)
Sex Differences
(P<)
140 ± 21 141 ± 23 .001#{176} #{149}05b
Apo B (mg/dL) 83 ± 21 83 ± 20 86 ± 22 86 ± 21 NS .Old
HDL-C (mg/dL) 58 ± 20 66 ± 20 55 ± 21 64 ± 20 #{149}001d oc
HDL-C/apo A-I ratio 0.42 ± 0.13 0.46 ± 0.12 0.40 ± 0.14 0.45 ± 0.12 .00l’ .00i
140 A-I
120 whIti, N925
.-. black, N=475
100
80 S
60
Age (years)
Apo A-I
o---o whlt#{149}, N=907 .-. black, N=543
Apo S
5 7 9 11 13 15 17 5 7 9 11 13 15 17
Boys
5-9yrs.
10-l4yrs.
15-l7yrs.
Girls
5* **
I*5
5*I
-4 -2 0 2 4 -.4 -2 0 2 4
160 Boys Girls
V
E
.
. 1 C a
a
Fig 3.
Changes in serum apolipoprotein (apo) B and apo A-I levels in boys and girls by age and race: Bogalusa Heart Study.5-8yrs.
9- l4yrs.
15-l7yrs.
Apo B Apo A-I
0 whlts
S
blackmg/di/y.ar (regression coefficient)
*p<O.05 **p<O.O1
Fig 4. Predicted yearly changes in serum apolipoprotein (apo) B and apo A-I levels in
boys and girls by race and age groups: Bogalusa Heart Study.
showed a progressive decrease in apo A-I levels
between the ages of 10 and 17 years.
Because apolipoprotein changes with age were
not linear, the relationship between these two
pa-rameters was estimated for specific age groups
based on piecewise regression technique. Predicted
yearly changes (milligrams per deciliter per year)
in apo A-I and apo B levels are shown in Fig 4.
Boys of both races showed significant yearly
incre-ments in apo A-I between the ages of 5 and 9 years
(2.2 mg for white boys v 4.1 mg for black boys) and
marked decrements between the ages of 10 and 14
years (-2.5 mg for boys of both races). The
declin-ing trend was reversed only in 15- to 17-year-old
black boys who showed significant yearly
incre-ments (3.4 mg). Among the girls, yearly changes in
apo A-I were significant for each age group only for
white girls whose values increased between 5 and 8
years (2.4 mg) and decreased between 9 and 14
years (-1.4 mg), followed by increases between 15
and 17 years (3.4 mg). Although black girls showed
similar trends in each age group, changes were
significant only in 15- to 17-year-olds (3.9 mg).
With respect to apo B, white girls showed a
significant yearly increase between the ages of 5
and 8 years (3.1 mg) followed by an equally
signif-icant decrease between the ages of 9 and 14 years
(-2.3 mg). Minimal changes were noted between
15 and 17 years of age in white girls. The yearly
changes by age group were not significant for other
race-sex groups.
The relationship of changes in HDL-C to changes
in apo A-I, with age, were evaluated in terms of
race-o---o whlt#{149}, N=926 .-. black, N=471
0 a
4
0 0. 4
(;)
-I a I C
a
a
o---o whlti, N=907 a-. black, N=543
S
0
5 . 7
.
9.
1’l ‘ 13 ‘ 15 17 0.55I
Boys Girls0.50’
0.45-0.40’
0.35
0.30
5 7 9 11 13 15 17
Age (years)
Fig 5.
Changes in high-density lipoprotein cholesterol (HDL-C) to apolipoprotein (apo)A-I ratio in boys and girls by age and race: Bogalusa Heart Study.
TABLE 3. Serum Levels of Apolipoproteins (Apo) A-I and B by Sexual Maturation*
Tanner Stage Tanner Stage v
Apolipoproteinst
1 2 3 4 5
Apo A-I (mg/dL)
White boys 143 ± 21 139 ± 20 136 ± 20 130 ± 20 132 ± 19 -0.231
White girls 141 ± 21 137 ± 22 137 ± 20 136 ± 18 142 ± 19 -0.04
Black boys 144 ± 20 146 ± 21 146 ± 24 140 ± 25 144 ± 23 -0.01
Black girls 141 ± 22 138 ± 23 135 ± 22 142 ± 27 144 ± 23 -0.03
Apo B (mg/dL)
White boys 84 ± 21 86 ± 20 83 ± 22 78 ± 23 80 ± 24 -0.08
White girls 88 ± 22 89 ± 22 83 ± 21 78 ± 19 80 ± 20 -0.16
Black boys 83 ± 19 86 ± 21 83 ± 20 80 ± 20 81 ± 23 -0.05
Black girls 87 ± 22 85 ± 19 86 ± 23 86 ± 20 83 ± 19 -0.07
* Values are means ± SD.
t Pearson correlation coefficients.
:tP<.0001
§
P < .05.specific mean ratios are shown in Fig 5. Boys from
both races showed a decrease in the ratio with age;
this trend was most pronounced in older white boys.
In girls of both races the ratio decreased between
the ages 5 and 1 1 to 12 years. Afterward, the ratio
increased until the age of 15 years, followed by
further decreases in white girls. Values in
17-year-old adolescents were lower than the values at 5
years of age in all race-sex groups except black
boys.
Effect
of Sexual
Maturation
Because adolescents of a given age express wide
variations in stage of sexual maturation, apo A-I
and apo B changes were also related to various
Tanner stages, an index ofphysiologic development
during adolescence (Table 3). Although secondary
sex characteristics are considered subjective, the
relationships with serum apo A-I and apo B can be
seen for Tanner stages. In adolescents the changes
of these apoproteins with maturation are quite
sim-ilar to those noted above with age, reflecting a close
association between developmental age and
chron-ologic age in the population as a whole. (Correlation
coefficients between age and Tanner stages for the
race-sex groups ranged from 0.79 to 0.87.) Of
par-ticular interest is the significant negative
relation-ship between apo A-I and sexual maturation seen
only in white boys. White children, especially girls,
showed an inverse association between apo B and
sexual maturation.
Relationship
to Serum
Lipids and Lipoprotein
Cholesterol
TABLE 4. Relationship of Apolipoproteins B and A-I
With Serum Lipids and Lipoprotein Cholesterol in White
(n = 1,830) and Black (n = 1,019) Children: Bogalusa
Heart Study*
ApoB ApoA-I
White Black White Black
Cholesterol
Total 0.77 0.761 0.39 0.37
Very low-density 0.48 0.38 -0.15 -0.04
lipoprotein
Low-density 0.93 0.92 0.06t 0
lipoprotein
High-density -0.36 -0.18 0.49 0.54
lipoprotein
Triglycerides 0.53 0.38 -0.13 0.01
Apo B 0.05t 0
* Pearson’s product-moment correlation coefficient.
tP< .05.
:I:P<.001.
§
Race difference, P < .01.serum lipids and lipoprotein cholesterol levels in
black v white children is presented in Table 4. In
both races, apo B was strongly related to both
LDL-C and total cholesterol and less strongly to
VLDL-C and triglycerides. A significant negative
correla-tion was noted between apo B and HDL-C. The
magnitude of the correlation of apo B with
triglyc-erides, VLDL-C, and HDL-C was less strong in
black children.
Apo A-I was moderately correlated with HDL-C
and to a lesser extent with total cholesterol.
How-ever, the association of apo A-I to HDL-C was not
as pronounced as the relationship between apo B
and LDL-C. A plot of apo A-I v HDL-C showed
that at a given level of apo A-I there was a wide
range of corresponding HDL-C levels (data not
shown). Although apo A-I was inversely correlated
with VLDL-C and triglycerides in white children,
no association was noted in black children. The
inverse relations of HDL-C to VLDL-C and
tn-glycenides occurred, as previously reported,9 in both
black and white children, and the relationships
were relatively stronger in whites than in blacks
(data not shown).
Serum Triglycerides-Apo A-I Associations
Because both serum triglycerides and VLDL are
inversely related to HDL,9’37 the differences in apo
A-I levels between black and white boys (blacks>
whites) is apparently consistent with the difference
in triglycerides (whites > blacks). To ascertain
whether this metabolic inverse relationship
be-tween these variables was entirely responsible for
the black-white differences, mean levels of
triglyc-erides and apo A-I by race were assessed separately
in boys and girls over each decile for apo A-I and
triglyceride relative deviates, respectively.
The formula (x - iRSA)/SRSA was used to
stand-ardize every child’s serum apo A-I or triglycerides
to the respective race-, sex-, age-specific group
(RSA).’#{176}For example, 144 mg/dL was the mean
(isA) apo A-I for all 10-year-old white boys and 21
mg/dL, the standard deviation (SRSA). A
10-year-old white boy with apo A-I level of 200 mg/dL
would have a relative deviate of (200 - 144)/21 =
+2.67. The corresponding value for another boy in
the same RSA with an apo A-I level of 100 mg/dL
would be -2.10. After relative deviates were
calcu-lated for all children, they were grouped in deciles.
Over each decile mean apo A-I or triglycerides were
determined for each race-sex group. The data are
shown in Fig 6.
Both white boys and white girls showed a steady
decline in triglycerides and apo A-I across the
higher deciles for apo A-I and triglycerides,
respec-tively (Fig 6). No such trend was noted in black
children. In boys black-white differences in
tniglyc-enide levels were discernible only at lower apo A-I
relative deviates. In contrast, the race-related
dif-ference in apo A-I levels in boys was not apparent
at higher deciles of triglyceride relative deviates. In
girls, although the black-white difference in
triglyc-enides was seen throughout the entire apo A-I
dis-tnibution, no such difference in apo A-I was noted
in relation to triglyceride distribution.
To determine triglycenide-apo A-I associations in
boys of both races, matching analyses based on
triglycerides (or apo A-I) and age were performed.
Mean apo A-I or triglyceride levels were then
corn-pared between the races. The results, Table 5, show
that the differences in apo A-I between black and
white boys who were matched for triglycerides and
age approached statistical significance only when
their triglyceride levels were high. Conversely, the
black-white difference in triglycerides among boys
who were matched for apo A-I and age became
apparent only when their apo A-I levels were low.
Selected
Percentiles
To estimate the statistical normal limits for
serum apo A-I and apo B in the pediatric
popula-tion, fifth and 95th percentile values by race, sex,
and age were determined and given in Tables 6 and
7, respectively. In addition, tenth percentile value
for apo A-I and 90th and 75th percentile values for
apo B were included as a guideline for identification
of a larger number of individuals who might be
potentially at risk for developing coronary heart
disease later in life.38 In general, consistent with
the race-, sex-, and age-related trends, the
percent-ile values for apo A-I differed between the races.
Boys Girls
C---O whlt#{149}, N 926 --o white, N 907
a-. black, N 478 .-#{149} black, N 543
- 80 0.
___o
o--, a \___o_.o..
----O---O---’Y-60
40
‘S
, 20
C a
a
a
_________________________0 r, ,
Apo A-I relative deviate deciles
I
::
‘ 130
C a
e
a 120
1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10
Low HIgh Low High
Triglycerides relative deviate deciles
Fig 6.
Serum triglyceride-apolipoprotein (apo) A-I associations in children by race, sex,and decile: Bogalusa Heart Study.
TABLE 5. Black-White Comparisons of Serum Triglycerides and Apolipoprotein A-I in
Matched Pairs*
Triglycerides Apolipoprotein A-I Age
(mg/dL) (mg/dL) (yr)
Triglycerides
53 mg/dL (261 pairs)t
White 41 ± 8 144 ± 21 9.7 ± 3.1
Black 42 ± 7 144 ± 21 9.7 ± 3.2
54 mg/dL (179 pairs)t
White 71 ± 16 140 ± 19 10.7 ± 3.7
Black 71 ± 15 144 ± 22 10.8 ± 3.7
Apolipoprotein A-I
141 mg/dL (215 pairs)t
White 59 ±
341:
126 ± 11 10.1 ± 3.7Black 54 ± 2O 126 ± 11 10.1 ± 3.7
142 mg/dL (231 pairs)t
White 55 ± 27 158 ± 12 10.1 ± 3.2
Black 53 ± 34 158 ± 12 10.1 ± 3.1
* Pairs are matched on apolipoprotein A-I or triglycerides and age. Values are means ±
SD.
t
Median values.:1:
P < .10 (paired t test).between boys and girls, the magnitude ofwhich was 17 years of age. With respect to apo A-I,
race-dependent upon age. related difference (blacks > whites) is seen only
among boys, in agreement with earlier findings in
DISCUSSION
adults
by
Tyroler et al.23 These authors have alsoThe present study describes the race-, sex-, and shown that the black-white difference in apo A-I is
age-related patterns of serum apo A-I and apo B in not completely accounted for by differences in
TABLE 6. Selected Percentile Values for Serum Apolipoprotein A-I in Children by Race,
Sex, and Age: Bogalusa Heart Study
Race and Boys Girls
Age (yr) n 5th 10th 95th n 5th 10th 95th
White
5-7 242 107 112 176 243 105 112 176
8-9 152 112 116 176 166 109 112 176
10-11 180 112 115 176 186 107 112 176
12-13 156 102 112 176 144 96 112 170
14-15 135 99 112 162 107 112 112 170
16-17 60 96 103 170 61 112 116 175
Black
5-7 127 104 112 172 138 104 112 192
8-9 84 112 122 176 99 112 112 176
10-11 98 122 128 176 85 96 110 18.8
12-13 55 107 112 193 78 96 106 192
14-15 63 107 112 176 75 109 112 177
16-17 51 111 118 192 68 107 112 192
TABLE 7. Selected Percentile Values for Serum Apolipoprotein B in Children by Race,
Sex, and Age: Bogalusa Heart Study
Race and Boys Girls
Age (yr) n 5th 75th 90th 95th n 5th 75th 90th 95th
White
5-7 242 51 92 104 115 243 53 96 113 120
8-9 152 53 93 104 114 166 58 104 117 143
10-11 180 57 96 108 120 186 59 102 120 132
12-13 156 50 93 106 123 144 50 90 112 120
14-15 135 48 88 104 112 107 45 88 104 117
16-17 60 52 96 109 151 61 45 88 103 106
Black
5-7 127 49 96 104 112 138 52 96 109 120
8-9 84 54 96 106 128 99 54 96 114 120
10-11 98 54 96 104 113 85 53 102 117 137
12-13 55 48 90 108 117 78 54 91 108 116
14-15 63 44 92 106 117 75 49 104 114 117
16-17 51 47 90 114 162 68 50 92 115 133
relatively higher in adults than in children of both
races.
The present findings demonstrate that a
signifi-cant black-white difference in apo A-I persists
among boys with almost identical triglyceride levels
provided that their triglyceride levels were in the
upper range of the distribution (Table 5). On the
other hand, the race-related difference in
tniglyc-enides among boys with almost identical apo A-I
levels is seen at low apo A-I levels. Because
triglyc-enides are inversely related to apo A-I in white
children but not in black children, the black-white
differences in apo A-I and triglycerides are likely to
become apparent at high and low levels of
triglyc-enides and apo A-I, respectively. However, it is of
interest that in girls race-related differences in
triglycerides persist at all levels of apo A-I; the
trend is not noted for apo A-I either at low or high
levels of triglycerides (Fig 6). It appears that the
black-white difference in triglycerides among girls
may not be totally attributable to the metabolic
inverse relationship between HDL and VLDL.37’39
These observations raise the possibility of some
intrinsic metabolic differences between the two race
groups.
The sex- and age-related changes in children
indicate a tendency for black girls to have lower
apo A-I and for girls of both races to have higher
apo B levels. In contrast, adult men (older than 20
years of age) show lower levels of apo A-I and higher levels of apo B than women.2224’4#{176} The
character-istic adult pattern seems to emerge during the latter
part of sexual maturation.
Although the age- and puberty-related
observa-tions are cross-sectional, the observed changes of a
large population probably reflect longitudinal
trends. Previously noted cross-sectional decreases
in HDL-C levels in white boys undergoing sexual
maturation14”5 parallel HDL-C longitudinal
de-creases observed in a cohort of white males from
the same Boys from both races
5 and 9 years, followed by marked decrements
be-tween 10 and 14 years of age (Fig 4). Girls,
espe-cially white girls, showed similar trends during
these age intervals. Of particular interest are the
changes that occurred among the four race-sex
groups in 15- to 17-year-olds. White boys continued
to show decrements during this age interval,
whereas black boys and girls of both races showed
increasing apo A-I Levels. No such changes in apo
B, with age, are seen among the race-sex groups,
except in white girls who showed increases between
the ages of 5 and 8 years followed by decreases.
The relationship of sexual maturation (Tanner
stages) to apolipoprotein changes is discernible only
in white children, with boys and girls showing
in-verse associations, respectively, for apo A-I and apo
B (Table 3). Earlier studies of children from this
community have shown that black children of each
sex progressed through each Tanner stage at an
earlier age than did white children.42 The divergent
changes in apolipoproteins during sexual
matura-tion probably reflect underlying physiologic and
metabolic differences related to race and sex.
Ap-parently, endogenous sex hormones are having a
major influence on the lipoprotein profile in
ado-lescents.43’44 In addition, the well-documented
ef-fects of smoking, alcohol, and oral contraceptives
on lipoprotein levels in older adults have been
dem-onstrated in adolescents as well.45’46 It is worthwhile
to understand the contribution of intrinsic (or
ge-netic) v environmental factors to the observed
dif-ferences during this transition period.
The continued decrease of apo A-I in white boys
during the transition to adulthood parallels the
HDL-C decrease seen previously in this race-sex
group.’4”5 The black-white differences in
lipopro-tein makeup appear to continue through
adult-hood.23’47 Because HDL is considered to be
antiath-erogenic,4’6’7 the adverse changes of apo A-I, as well
as HDL-C in white males, may target this group
for accelerated atherosclerosis and future coronary
heart disease. The greater incidence of coronary
heart disease among white men than black men
seems to support such views.48
The relationships of apo A-I and apo B to lipids
in different lipoprotein cholesterol fractions are in
the expected directions, given the metabolic and
functional associations among them.’7’37’39 The
oh-served black-white differences in the above
rela-tionships suggest differences in lipoprotein makeup
between the two groups. For example, relatively
lower levels of VLDL-C (or triglycerides) in black
children without any difference in apo B levels
would result in lower correlation between these
variables in the black compared to white children.
The finding that the relation of apo A-I to
HDL-C in children is not strong indicates the possibility
of heterogeneity among HDL particles, eg,
occur-rence of varying proportions of HDL2 and
HDL3.49’5#{176}It is known that HDL2 carries about
twice as much cholesteryl ester molecules per mole
of apo A-I compared to HDL3 and that the HDL
components, cholesterol and apo A-I, arise
inde-pendently through metabolic interconversions of
lipoproteins.37 Unlike HDL3, HDL2 differs
mark-edly among individuals and accounts for the
varia-bility of total HDL.50’5’ Therefore, any variability
in HDL subfractions among individuals is expected
to result in various levels of cholesterol for a given
amount of apo A-I. The variability in HDL-C, in
relation to apo A-I, may also be in part due to the
exchange of cholesteryl esters for triglycerides
be-tween HDL and VLDL, resulting in a decrease in
HDL-C with increasing triglycerides (VLDL).24’52
The possibility of race- and sex-related
differ-ences in HDL subpopulations is further supported
by the finding that the HDL-C/apo A-I ratio differs
by race (black > white) and by sex (boys > girls,
especially among white children). A higher ratio of
HDL-C/apo A-I suggests an increase in HDL2 in
proportion to HDL3.22 Recently, Tyroler et al23
found higher apo A-I/apo A-Il ratios in adult
blacks, especially men. Because the apo A-I/apo
A-II ratio is higher in HDL2 than in HDL3,53 these
authors hypothesized that HDL2 may be relatively
higher among blacks. Our results in children seem
to support this view. Although women are known
to have higher HDL2 than men,37’51 our findings
that younger white boys have a higher HDL-C/apo
A-I ratio than younger white girls suggest an
op-posite pattern in childhood. That marked changes
occur with HDL subfractions during childhood is
seen from the alterations in HDL-C/apo A-I ratio
with age.
Although the fifth and 95th percentiles may be
statistically valid normal population limits, they
are arbitrary and do not necessarily represent the
optimal levels with respect to coronary heart
dis-ease risk. It should be noted that some of the age-,
race-, and sex-specific percentiles provided here are
based on a relatively small number of observations.
Additional comparative data in pediatric
popula-tions living in different cultural and geographic
environments within the country may be necessary
for obtaining more accurate normal limits. Because
coronary heart disease is widely prevalent in the
population at large, less rigid limits are outlined by
including 90th and 75th percentiles for apo B and
the tenth percentile for apo A-I. These observations
will serve as baselines for comparison with other
interven-tion, especially when a family history of coronary heart disease is present.
ACKNOWLEDGMENTS
This research was supported by grant HL 02942 from the National Heart, Lung, and Blood Institute of the Public Health Service and grant HL 15103 from the National Research and Demonstration
Center-Arterio-sclerosis.
We are grateful to the children of Bogalusa and their
parents, without whom this work would not have been possible. We thank the Bogalusa Heart Study staff for
data collection and the National Research and
Demon-stration Center-Arteriosclerosis Core Laboratory staff, especially Rajini Sharma and Mildred Caro, for technical
assistance.
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ANNOUNCEMENT
The European Society for Pediatric Research will hold its next meeting in
Groningen, The Netherlands, Sept 7-10, 1986. The following Working Groups
will join the meeting: Paediatric Allergy and Clinical Immunology, Paediatric
Pharmacology, and Perinatal and Paediatric Microcirculation. The main topics
are Nutrition and Metabolism, Hepatic Metabolism, Fetal and Neonatal
Me-tabolism, Developmental Neurology, Genetics Immunology, Pharmacology,
Mi-crocirculation, and Oncology.
For young investigators, particularly from Eastern Europe, travel bursaries
are available. For information and participation contact: J. Fernandes,
Depart-ment of Paediatrics, University Hospital, 59 Oostersingel, 9713 EZ Groningen,