Relation of Cholesterol to Apolipoprotein B

in Low Density Lipoproteins of Children

The Bogalusa Heart Study

Sathanur R. Srinivasan, Wendy Wattigney,

Larry S. Webber, and Gerald S. Berenson

Cholesterol and apolipoprotein (apo) B contents and their relationship within

serum low density llpoprotein (LOL) were examined In 2018 children, ages 8 to 17
years, from a blraclal community. The levels of LDL cholesterol and LDL apo B
showed significant race-related differences (blacks>whltes) in both boys and girls
and gender-related differences (glrts>boys) In white children. These LDL measures
associated Inversely and significantly with both age and Tanner stage, more so in
boys than In girls. The black-white differences In LDL measures persisted after
adjusting for the covarlates (sexual maturation, age, adiposity, oral contraceptive
use, cigarette smoking, and alcohol use). The distribution of LDL cholesterol for a
given range of LDL apo B varied considerably, despite a strong correlation (r =0.91)
between these variables, Indicating that measuring LDL cholesterol alone does not
accurately reflect LDL concentration. The ratio of cholesterol to apo B In LDL ranged
from 1.01 (5th percentlle) to 1.42 (95th percentlle) among the four race-gender
groups, suggesting marked InterlndMdual variation In composition. That this ratio
was significantly elevated In black children Indicates the occurrence of relatively
larger, less dense, and cholesterol-enriched LDL particles In blacks. Significant
Independent associations were noted between LDL cholesterol/apo B ratios and the
levels of serum total cholesterol (positive) and trlglycerldes (negative), suggesting
the Influence of pool size of different lipoproteins on LDL composition. These
observations may help identify a subgroup of children with apo B-enriched LDL
particles who are potentially at risk for coronary artery disease.
(Arteriosclerosis 9:493-500, July/August 1989)
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S erum lipoproteins are important risk factor variables

for coronary heart disease (CHD), with low density
lipoproteins (LDL) and high density lipoproteins (HDL) show-
ing positive and inverse risk associations, respectively.1-^
Recent studies by Sniderman and colleagues4 indicate that
many patients with CHD have elevated levels of LDL apo-
lipoprotein (apo) B but normal levels of LDL cholesterol.
Kesanierni and Grundy5 reported that some patients with
CHD have increased ratios of apo B to cholesterol in LDL
and abnormalities in LDL apo B metabolism despite normal
concentrations of LDL
That the LDL particles are heterogeneous in terms of
both size and composition even in normal individuals is
now well recognized. 878 However, no population-based
data are currently available regarding the variability in
LDL Although the LDL particles differ in size and lipid
content, they contain one molecule of apo B per particle.
The larger LDL particles with less density have a higher
From the Departments of Medicine, Biochemistry, and Biome-
try and Genetics, Louisiana State University Medical Center, New
Orleans, Louisiana.
This study was supported by research Grants HL 38844 and
HL02942 from the National Heart, Lung, and Blood Institute of the
U.S. Public Health Service.
Address for reprints: Gerald S. Berenson, M.D., Department of
Medicine, LSU Medical Center, 1542 Tulane Avenue, New
Orleans, LA 70112.
Received November 9, 1988; revision accepted February 28,
1989.
cholesterol/apo B ratio than the smaller and denser par-
ticles. Therefore, measurements of cholesterol and apo B
in LDL offer one of the means by which variability in LDL
can be examined on a population basis.
Since CHD risk factor variables are related to initial
stages of atherosclerosis in the young,9 it is important to
study the serum lipoproteins in children. Serum lipoprotein
lipid and apolipoprotein distributions in U.S. children from
population-based studies are currently available.10-14 Of
these, the Bogalusa Heart Study provides data on a
biracial (black-white) pediatric population. In addition to
the race, gender, and puberty-related differences in certain
lipoproteins, our studies show that variability in lipoprotein
composition occurs in a general population of children.1518
For example, a marked interindrvidual variation was found
in the composition of HDL with the ratio of cholesterol to
apo A-l in HDL ranging from 1:4to 1 -2 between the 10th
and 90th percentiles. Similar variability in the relation of
cholesterol to apo B in LDL might be expected.
The objective of the current study was to examine the
variability in the relation of apo B to cholesterol in LDL of
children from a biracial community. Factors that influence
LDL composition were also determined.
Methods
Population
The Bogalusa Heart Study is a long-term epidemiologic
study of cardiovascular disease risk factors from birth

493
 494 ARTERIOSCLEROSIS
Table 1. Measurement Error for Serum Low Density Llpoproteln Cholesterol and Apollpopro-
teln B Determinations. The Bogalusa Heart Study
Mean
No. of
pairs Original Replicate
Variable (blind) (mg/dl)
LDL cholesterol 260 96.5
LDLapoB 260 89.4
LDL=fow density lipoprotein, SD=standard deviation, CV=coefflctent of variation, apo=apolipoprotein.
through earty adulthood in the biracial community (65%
white, 35% black) of Bogalusa, Louisiana. During 1984
and 1985, 2666 children in grades 3 to 12 representing
85% of all eligible individuals were examined. Children
younger than 8 years or older than 17 years were excluded
(n=107) because they were not representative of those
attending grades 3 to 12. In addition, 345 nonfasting
participants and 214 children with any missing laboratory
data (primarily due to lack of adequate serum samples for
LDL apo B and LDL cholesterol measurements) were
excluded from the analysis, yielding a final sample size of
2018. In this group, there were 66% whites and 34%
blacks, 49% boys, and 5 1 % girls, reflecting the race-
gender distribution of the community.
Anthropometrlc and Lifestyle Examinations
Sexual maturation was determined by visual assess-
ment of secondary sex characteristics during a physical
examination according to the method of Tanner.17 The
ratings for sexual maturation ranged from 1 (no develop-
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ment) to 5 (complete development) according to the
stages of female breast or male genitalia development.
Subscapular sklnfold thickness was measured and used
as a measure of adiposity.
Information on lifestyle characteristics was obtained by
questionnaires concerning smoking (number/week, grades
3 to 12), alcohol intake (ml/week, grades 7 to 12), and oral
contraceptive use (girls, grades 7 to 12).18
Collection of Blood Specimens
Children were instructed to fast for 12 to 14 hours, and
compliance was determined by interview on the morning
of examination. Serum samples were obtained from ante-
cubital venous blood and were sent in a cold-packed box
to the New Orleans Core LJpid Laboratory where they
were kept at 4°C. Laboratory analyses were performed on
the following day.
A second blood sample (blind duplicate) was collected
on each screening day (an approximate 10% random
subsample) to estimate measurement error.
Serum Llplds
Cholesterol and triglyceride were determined in a Tech-
nicon Auto-Analyzer II (Technicon Corporation, Tarry-
town, NY) according to the laboratory manual of the LJpid
Research Clinics Program.19 The laboratory has been
designated as standardized by the Centers for Disease
Control (CDC) in Atlanta, Georgia, and currently is in the
surveillance phase of its quality control program.
VOL 9, No 4, JULY/AUGUST 1989
Measurement error
Intradass
SD CV correlation
(mg/dl) (%) coefficient
97.1 5.6 5.8 0.94
89.8 5.2 5.7 0.93
Low Density Llpoproteln Cholesterol and
Apollpoproteln B
The cholesterol and apo B contents of serum LDL were
measured directly by selectively precipitating this lipopro-
tein with heparin at pH 5.11 according to the method of
Wieland and Seidel,20 which was based on the original
observation by Burstein.21 Briefly, 200 /tl of the sample is
added to 2 ml of buffered heparin (0.064 M trisodium
citrate, 50 000 U/l heparin) and vortexed. After 10 minutes
of standing at room temperature, the insoluble LDL fraction
is sedimented by centritugation at 1000 g for 10 minutes.
The precipitate is dissolved in phosphate-buffered isotonic
saline (pH 7.4), and aliquots are taken for assay of choles-
terol and apo B. The determination of LDL cholesterol by
this procedure showed an excellent agreement with results
obtained by ultracentrifugation in combination with potyan-
ionic precipitation (cholesterol content of d>1.006 g/ml
infranate fraction minus cholesterol content of heparin-
Mg ++ supemate).20 Therefore, we considered this method
practical for large epidemiologic studies such as ours.
Apo B in LDL was determined by the electroimmunoas-
say procedure of Laurell22 as described elsewhere in
detail.14 Antibodies to LDL (d=1.03 to 1.05 g/ml) raised in
a goat were used. The candidate international standard
serum pool for apo B quantitation was obtained from the
CDC and was used to standardize an in-house secondary
standard serum pool. The laboratory is participating in the
apolipoprotein standardization program of the Interna-
tional Union of Immunological Societies, CDC, and the
National Heart, Lung, and Blood Institute.
The measurement errors for LDL cholesterol and LDL
apo B are given in Table 1. Because two independent
samples were collected from each of 260 individuals, the
measurement errors include errors associated with collec-
tion, processing, and analysis of the samples, as well as
with data processing. Both LDL cholesterol and LDL apo B
had equally high intradass correlation coefficients, reflect-
ing the same degree of reliability of measurement.
Statistical Analyses
Race and gender differences in levels of LDL measures
were examined by t tests. The relation of LDL measures to
age and sexual maturation (Tanner stage) were assessed
with Spearman (rank-order) correlation coefficients within
each race-gender group. Analysis of covariance was used
to determine if black-white differences in mean levels of
LDL measures persisted after appropriately controlling for
Tanner stage, age, age2, age3, subscapular sWrrfokJ thick-
ness, cigarette smoking, alcohol consumption, and oral
contraceptive use.
 LDL CHOLESTEROL AND APO B IN CHILDREN Srinivasan et al. 495

Spearman correlation coefficients were computed to MALES FEMALES

examine the interrelationships among serum lipids and
LDL measures separately for whites and blacks. Variability
in the mean LDL cholesterol/apo B ratio among different
strata of serum lipid levels (quintiles) were examined by
analysis of variance; Duncan's method was used to test all
pairwise differences among quintile means.23 Significant
predictors of LDL cholesterol/apo B ratio were identified
using a stepwise regression procedure24; the independent 50 DO 150 50 DO BO
variables included serum lipids, age, race, gender, Tanner mg/d
stage, subscapular skinfold thickness, cigarette smoking,
alcohol consumption, and oral contraceptive use.
The levels of LDL cholesterol and LDL apo B were divided
into quintiles, and these categories were then cross-
tabulated to examine separately the percent distribution of
LDL cholesterol quintiles within each LDL apo B quintile.

Results 50 DO 6 0 50 DO W
Distribution and Mean Levels mg/dl
The race- and gender-specific cumulative frequency
distributions of LDL apo B, LDL cholesterol, and LDL
cholesterol/apo B ratio are shown in Figure 1; the mean
levels by race and gender are given in Table 2. The
median and mean values for these variables were almost
identical. Overall, the values for these LDL measures
were significantly higher in black children than in white
children, irrespective of gender. A significant male-female
difference in LDL apo B and LDL cholesterol levels, with
girls showing higher values than boys, was noted only U
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among white children. No such gender-related difference

in LDL cholesterol/apo B ratio was apparent in either black
or white children. The ratio of cholesterol to apo B in LDL
ranged from 1.01 (5th percentile) to 1.42 (95th percentile)
among the four race-gender groups.
Figure 1. Cumulative frequency distribution (%) of serum low
density lipoprotein (LDL), apdipoprotein (apo) B, LDL choles-
terol, and LDL cholesterol/apo B ratio In children by race and
gender. The Bogalusa Heart Study.

Distribution of Low Density Llpoproteln Relation to Age and Sexual Maturation

Cholesterol Relative to Apollpoproteln B
In view of the wide range in the ratio of cholesterol to
apo B in LDL, the prevalence of variability in LDL choles-
terol levels for a given range of LDL apo B was examined
by tabulating frequency distribution of LDL cholesterol
quintiles according to LDL apo B quintiles (Table 3). The
values across each row represent percentages of the
children within a given LDL apo B quintile (shown on the
left) having different LDL quintiles (shown at the top). If the
stoichiometric relation between the cholesterol and apo B
constituents of LDL remained constant, one would expect
a 100% frequency within cells representing identical LDL
apo B and LDL cholesterol quintiles (e.g., quintiles 1-1,
2-2,3-3, etc.). Instead, the children within each LDL apo B
quintile were distributed among different LDL cholesterol
quintiles. Of the children belonging to the first, second,
third, fourth, and fifth LDL apo B quintiles, only 79.3%,
51.5%, 41.0%, 52.7%, and 78.9%, respectively, remained
in the corresponding LDL cholesterol quintiles. Further-
more, children in the extreme LDL apo B quintiles showed
relatively higher concordance with corresponding LDL
cholesterol quintiles; the opposite was true for children in
the middle LDL apo B quintile.
Race-, gender-, and age-specific mean levels of LDL
apo B, LDL cholesterol, and LDL cholesterol/apo B ratio
are shown in Figure 2. The levels of LDL apo B and LDL
cholesterol showed a decrease with age, especially
between the ages of 10 and 14 years in boys and 8 and 13
years in girls of both racial groups; afterwards, the levels
tended to fluctuate towards higher values. By comparison,
the levels of LDL cholesterol/apo B ratio by age showed
no discernible trend in the four race-gender groups,
except that the values remained remarkably low in white
boys compared to other race-gender groups between the
ages of 15 and 17 years. Overall, the cross-sectional
correlations of LDL apo B and LDL cholesterol to age
were negative and significant in all the race-gender groups,
with boys (r=-0.2O to -0.24, /K0.0O1) showing relatively
higher correlations than girls (r=-0.12 to -0.17, p<0.01),
whereas the correlation of LDL cholesterol/apo B ratio to
age was not significant in all the cases (r=-0.08 to 0.08.)
Because adolescents of a given age express wide
variations in their stage of sexual maturation, the serum
variables were also related to various Tanner stages, an
index of physiologic development during adolescence.
The results were similar to those noted above with age.
 496 ARTERIOSCLEROSIS VOL 9, No 4, JULY/AUGUST 1989

Table 2. Serum Levels of Low Density Upoproteln (LDL) Apolipoprotein (Apo) B, LOL Choles-
terol, and LDL Cholesterol/Apo B Ratio In Children by Race and Gender. The Bogalusa Heart
Study
Boys Girls
White Black White Black Race Gender
(n=646) (n=342) (n=683) (n=347) difference difference
LDL apo B (mg/dl) 80+18 84±18 83±17 87±18 p<0.01 /X0.01*
LDL cholesterol (mg/d!) 93±23 100+24 96+22 102±23 p<0.001 p<0.01*
LDL cholesterol/apo B 1.16±0.12 1.19±0.13 1.16±0.11 1.18+0.11 p<0.05 NSt
"Whites only, fNot significant

Table 3. Frequency Distributions of Low Density Upoproteln (LDL) Cholesterol Qulntiles

according to LDL Apolipoprotein B Qulntiles In Children. The Bogalusa Heart Study
. n. R LDL cholesterol quintiles (mg/dl)
quintiles 1 2 3 4 5
(mg/dl) (38-77) (78-90) (91-100) (101-114) (115-206) N*
1 (29-68) 79.3 18.0 2.0 0.5 0.2 411
2 (69-77) 19.5 51.5 20.7 7.6 0.7 406
3 (78-86) 0.3 32.2 41.0 23.4 3.1 385
4 (87-97) 0 5.8 23.4 52.7 18.1 414
5(98-145) 0 0 1.7 19.4 78.9 402
Values are percent frequency.
'Number of children within LDL apo B quintile.
LDL=k>w density lipoprotein, apo=apoHpoprotein.

Both LDL cholesterol and LDL apo B associated inversely
with Tanner stage, more so in boys (r=-0.26 to -0.29,
p<0.001) than in girls (r=-0.11 to -0.16, p<0.01). On
the other hand, no significant correlation was noted
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apoB correlated to LDL cholesterol (r=0.37 to 0.40,
p<0.001) but did not correlate to LDL apo B (r=-0.01 to
0.01) even though the ratio contains both the original
variables. This suggests that cholesterol, rather than

between Tanner stage and LDL cholesterol/apo B ratio
(r=-0.08to0.07).
Evaluation of Black-White Differences
Black-white differences in LDL apo B and LDL choles-
terol levels were examined for boys and girls separately,
controlling for potential confounding covariates (sexual
maturation, age, adiposity, cigarette smoking, alcohol
use, and oral contraceptive use) (Figure 3). The observed
differences in LDL apo B and LDL cholesterol were
independent of the above confounding factors, with covar-
iant-adjusted values for LDL apo B showing 8.2% and
4.7% higher in black boys (p<0.001) and black girls
(p<0.001), respectively, than their white counterparts.
The covariate-adjusted levels of LDL cholesterol remained
higher in black boys (11.6%, p<0.001) and black girls
(6.2%, p<0.001). Black-white differences in LDL choles-
terol/apo B ratio also persisted in both boys (3.0%,
px0.001) and girls (1.6%, p<0.05) after adjusting for the
covariates (data not shown).
Influence of Serum Llplds on Low Density
Upoproteln/Apolipoprotein B Ratio
Serum total cholesterol correlated positively and signif-
icantly to LDL cholesterol/apo B ratio in both races
(r=-0.33 to 0.38, p<0.001); in contrast, serum triglycer-
ides showed an inverse relationship (r=-0.13 to -0.17,
p<0.001). As expected, LDL apo B showed a strong
positive correlation to LDL cholesterol in both races (r=0.90
to 0.91, p<0.001). The ratio of LDL cholesterol to LDL
apo B, varies within LDL
Since serum total cholesterol and triglycerides showed
opposing relations to LDL cholesterol/apo B ratio, the
variability in the mean levels of this ratio was examined in
relation to a range of levels (quintiles) of serum iipids
(Figure 4). Gradients in the levels of LDL cholesterol/apo B
ratio were evident over quintiles of both serum total cho-
lesterol (a positive trend, p<0.001) and triglycerides (an
inverse trend, p<0.001). Furthermore, mean levels of LDL
cholesterol/apo B ratio among various total cholesterol and
triglyceride quintiles were significantly different from each
other (p<0.05), with the exception of a lack of difference in
values noted between second and third triglyceride quin-
tiles. The mean values for LDL cholesterol/apo B ratio
ranged from 1.11 to 1.22 among total cholesterol quintiles,
and from 1.14 to 1.19 among triglycerides quintiles.
A stepwise regression procedure was then used to
identify covariates (including serum total cholesterol and
triglycerides) that were all independently related to LDL
cholesterol/apo B ratio (Table 4). Serum total cholesterol
and triglycerides accounted for 16% of the variability in LDL
cholesterol/apo B ratio. Other covariates such as age, race,
gender, Tanner stage, subscapular skinfold thickness, cig-
arette smoking, and oral contraceptive and alcohol use
contributed less than 2% to the variations of the ratio.
Discussion
The present community-based study provides race-,
gender-, and age-specific levels of cholesterol and apo B
 LDL CHOLESTEROL AND APO B IN CHILDREN Srinivasan et al. 497

MALES FEkALES HALES FEMALES

LDL LDL U)L LDL

Apo B Cholesterol Apo B Cholesterol

77A AdjiBbdfor
cowiutes
R g u r e 3. Black-white differences in low den- * p < 0D1
sity lipoprotein (LDL) apolipoprotein (apo) B and * * p < 1001
LDL cholesterol levels after controlling for selected
covariates (Tanner stage, age, age 2 , age 3 , sub- Cowriates
scapular skinfold, oral contraceptive use, ciga- A?
124- rette smoking, and alcohol use). The Bogalusa Tarrer Stage

*
LDL CHOLESTEROL/Apo B Stincaptior S
Heart Study.
Ord Contraceptive
.120- Cigarette SmotaQ
Alcohol Use

s
CO

1
o 122-

118-

1i § ii
0 1 2 1 4 1 6 8 D 12 14 «
Age (years)

V//////A
114-
Rgure 2. Mean levels of serum low density lipoprotein (LDL),
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apolipoprotein (apo) B, LDL cholesterol, and LDL cholesterol/ IX)-

apo B ratio in children by race, gender, and age. The Bogalusa
Heart Study.
and their relative proportion within LDL in children and
adolescents. Our findings that small, but consistent, black-
white differences in both LDL cholesterol and LDL apo B
occur, with blacks showing higher values than whites,
indicate relatively higher LDL particle numbers in blacks.
Earlier studies by us14 and Morrison et al. 25 did not detect
black-white differences in LDL cholesterol, probably
because cholesterol measurements were not performed
directly on isolated LDL fractions, as in the present study.
Furthermore, we did not find black-white differences in
fasting serum total apo B,14 which represents all the
lipoproteins except HDL. This is to be expected, in view of
the present finding, because serum levels of very low
density lipoproteins (VLDL) are relatively lower in blacks
as compared with whites.11 •» The opposing trends in LDL
and VLDL levels between the two racial groups might
result in similar total apo B values.
The black-white divergences in LDL cholesterol and
LDL apo B persisted even after adjusting for the confound-
ing covariates such as sexual maturation, age, adiposity,
oral contraceptive use, cigarette smoking, and alcohol
use. The possibility exists, however, that the observed
black-white differences may be party due to lipoprotein
Lp(a), the serum levels of which have been found to be
higher in black individuals.26 Lipoprotein Lp(a), which
includes apo B, apo (a), and cholesterol, is known to
1.06 83- M l - 6 7 - 170- B8- 6- 44-55-68-90-
MO 66 169 «7 316 43 54 67 89 339
TOTAL CHOLESTEROL TRIGLYCERtDES
Quintiles (mg/dl)
Rgure 4. Mean low density lipoprotein (LDL) cholesterol/apo-
lipoprotein (apo) B ratio by serum total cholesterol and triglycer-
ide quintiles. Hatched bar with an asterisk denotes that the ratio
is significantly (p<0.05) different from the ratios for the rest of the
quintiles. The Bogalusa Heart Study.
interact with heparin, but the extent of precipitation of
Lp(a) by heparin is negligible in the absence of Ca + + . 2 7
Since lipoprotein Lp(a) represents less than 3% and 5% of
serum total cholesterol in white and black individuals,
respectively,26 any contribution of lipoprotein Lp(a) in
quantitative terms to LDL measures in the precipitation
procedure devoid of Ca ++ should be minimal.
The present data show a gender differential (girls>boys)
in both LDL cholesterol and LDL apo B only among white
children. Furthermore, the cross-sectional associations of
LDL measures with age and sexual maturation remained
negative, more so in boys than in girls. These findings in
conjunction with earlier observations in children 2829 and
adults 3031 indicate that the characteristic adult pattern of
elevated levels of LDL in men versus women emerges
after completion of sexual maturation.
 498 ARTERIOSCLEROSIS
Table 4. Linear Regression Model Estimating Low
Density Upoproteln Cholesterol/Apolipoprotein B Ratio
In Children. The Bogalusa Heart Study
Regression Standard
Independent variable coefficierrt error R2
Serum total cholesterol 1.66x10"^ 0.0001 0.111
Serum triglycerides -7.29x10"*t 0.0001 0.161
Age 6.24x10-^ 0.001 0.173
Oral contraceptive use -9.42x10~ 1 t 0.019 0.185
Subscapular skinfotd
thickness -8.82x10-"* 0.0003 0.188
2
Overall F=85.11 (p<0.001), f? =0.188, mean square error=
0.01, intercept=0.88.
*p<0.05, tp<0.001.
Of particular interest is our finding that marked interin-
dividual variations in the composition of LDL particles
exists among children. The variability in LDL is evaluated
in terms of cholesterol to apo B ratio within LDL because,
with decreasing ratio, the particles become smaller and
denser and carry less core lipid. 8 3 2 3 3 3 4 In children, the
ratio of cholesterol to apo B within LDL varied from 1.01 to
1.42 between the 5th and 95th percentiles. Furthermore,
this ratio was significantly higher in black children than in
white children, suggesting that LDL particles are relatively
larger, less dense, and more cholesterol-enriched in the
former group. It appears that the black-white difference in
LDL is not only quantitative, but qualitative as well.
Despite a strong correlation between LDL apo B and
LDL cholesterol (r=0.91), the distribution of LDL choles-
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terol for a given range of LDL apo B varied considerably.
For example, of the 385 children who belonged to the third
LDL apo B qumtile, only 158 (41%) remained in the same
LDL cholesterol quintile. It is, therefore, obvious that, even
in a general population of children, measuring LDL cho-
lesterol alone does not accurately reflect LDL concentra-
tion (particle number). Moreover, as Teng et al. 8 pointed
out, important differences in composition may be missed if
only LDL cholesterol is measured.
The interrelationships of serum lipids and LDL mea-
sures noted in the present study support the hypothesis
that serum triglyceride (VLDL) concentration influences
the characteristics of LDL 3 5 ' 3 8 3 7 Our results show that
graded changes in the relative proportions of cholesterol
to apo B within LDL are inversely and continuously related
to serum triglyceride levels and positively to serum total
cholesterol levels. Moreover, both serum total cholesterol
and triglycerides remained as the predominant significant
predictor variables for the LDL cholesterol/apo B ratio.
Deckelbaum et al. 38 reported a strong inverse association
(r=-0.64) between serum triglyceride levels and the ratio
of cholesteryl ester to protein in LDL; however, the study
subjects (n=43) varied from individuals with extremely
low triglyceride levels (abetalipoproteinemia) to those with
hypertriglyceridemia (Types I and IV). It is noteworthy that
serum triglyceride level is a significant determinant of LDL
cholesterol/apo B ratio in a free-living population of chil-
dren with a median triglyceride level of 56 mg/dl. That the
divergence in LDL cholesterol/apo B ratio between the
racial groups (blacks >whites) reflects difference in serum
VOL 9, No 4, JULY/AUGUST 1989
triglyceride levels between the two groups (white > blacks)
further demonstrates the influence of serum triglycerides
on LDL composition.
Recently Barter et al. 38 demonstrated that exchange of
cholesteryl ester between lipoproteins is a function of the
pool size of different lipoprotein fractions. In a related
study, we found that children with low VLDL triglycerides
had a higher ratio of cholesterol to triglycerides in lipopro-
tein fractions (VLDL, LDL, and HDL) and vice versa.16
Taken together, it appears that increased serum triglycer-
ide levels (VLDL) would result in decrease in cholesterol
as compared with apo B in LDL particles. By comparison,
increased serum total cholesterol levels (LDL) under
conditions of low serum triglyceride levels would produce
an opposite effect.
The alterations in LDL size, density, and composition
are considered to be due to the bidirectional transfer of
triglycerides and cholesteryl ester between VLDL and LDL
mediated by lipid transfer protein. 3940 The triglyceride-
loaded LDL is then subject to hydrolysis by hepatic lipase
and lipoprotein lipase, resulting in smaller and denser
particles with lower cholesterol/apo B ratio. It was recently
suggested that the ratio of cholesterol to apo B in LDL
could be a reflection on the turnover rates of LDL.5 41 The
observed variability in LDL cholesterol/apo B ratio, although
relatively modest, may nevertheless reflect the heteroge-
neity of LDL metabolism on a population basis.
Recently, it was reported that genetic polymorphism in
apo B is reflected in the general population.4243'44 The
structural differences in apo B, probably resulting from an
alteration in its amino acid sequence, may influence the
LDL composition in normolipidemic individuals. It is unclear
how much of the variability in LDL seen in the current
study is due to genetic heterogeneity. It should be noted,
however, that only 18.8% of the variability in LDL choles-
terol/apo B ratio is explained by the independent variables
listed in Table 4.
Our observation that variability in LDL composition
occurs among free-living, healthy children may have a
bearing on CHD risk. Earlier we showed that the LDL
cholesterol/total apo B ratio was significantly higher in
children with paternal myocardial infarction.45 With tech-
nological advances allowing routine measurement of apo
B in a reliable manner, information on the relative propor-
tion of cholesterol to apo B within LDL can have practical
merit. For example, a subgroup of children with dispropor-
tionate increase in apo B relative to cholesterol in LDL
may be at an increased risk because of the atherogenic
potential of such LDL particles. 446 Furthermore, it is likely
that the preponderance of early coronary artery disease in
white men compared to other race-gender groups47 may
be due in part to characteristic difference in LDL. It is of
interest that LDL particles are relatively apo B-enriched in
white children (especially in adolescent white boys) com-
pared to black children, although particle numbers are
higher in the latter. If the compositional difference in LDL
continues through adulthood, this may confer additional
CHD risk on white men because the levels of antiathero-
genic HDL (cholesterol and apo A-l) are relatively low in
this group compared to other race-gender groups. 1114 - 2S48
Further studies in this direction are obviously needed.
 LDL CHOLESTEROL AND APO B IN CHILDREN
Acknowledgments
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 field staff for data collection and the
Core laboratory staff, especially Rajini Sharma and Mildred Caro,
for technical assistance.
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Index Terms: low density lipoprotein composition • LDL cholesterol LDL apolipoprotein B
• white children • black children
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