Metabolism Clinical and Experimental VOL. XXVI,
NO. 4
PRELIMINARY
Cord in
blood
117
J.
assess
for
racial
lipid
black
and
differences density low-density
Similarities in Cord Blood Lipids and Lipoproteins
Glueck, P. S. Gartside,
lipoproteins
neonates
(58
were white,
potential
C-HDL/C-LDL,
black)
to
glycerides
of
neonates
of
adult
no
the
there
were
(TC),
cholesterol
lipoprotein
Mellies, and P. M. Steiner
expression
cholesterol
lipoprotein
M.
In comparison
neonates
in total
R. C. Tsang,
quantitated 50
early
distinctions. white
1977
REPORT
Black-White C.
APRIL
cholesterol
high-
(C-HDL), (C-LDL),
or C-HDL/TC. were (p
=
black-white limits
cord blood
of
higher
0.02).
Unlike
comparisons
“genicity”
lipoproteins,
cial differences
Cord
slightly
in C-HDL,
as there
blood in
certain and
within
expressed were
C-LDL,
tri-
black
and
by
no ratotal
cholesterol.
UBSEQUENT to finding an excess of coronary artery disease in Evans County, Ga., whites,’ Tyroler et al. reported “. . . higher LDL [low-density lipoprotein] cholesterol and total triglycerides are present in whites, and higher HDL [high-density lipoprotein] cholesterol was found in blacks in an age, sex, and total serum cholesterol matched comparison.” Tyroler et al. found no race-related differences in occupation, education, social class, or smoking habits and suggested a “possible genetic origin” for the lipoprotein differences.’ Although Tyroler et al. acknowledged that the black-white differences in coronary disease were consistent with “either the atherogenicity of the higher VLDL [very-low-density lipoprotein] and LDL cholesterol and total triglycerides of white males or the protectiveness of higher HDL cholesterol in black males . . . ,” the negative coronary-risk-factor status of HDL2,3 was emphasized. In the current study, possible “genetic” black-white lipoprotein differences’
S
From the Clinical Research and Lipid Research Centers and the Department of Epidemiolog) and Biostatistirs. University of Cincinnati College of Medicine.Cincinnati. Ohio. Received&v publication September 22, 1976: Supported in part bjl GCRCgranr RR-0006X-14. A portion of this work was done during Dr. Glueck’s tenure as an established investigator of the American Heart Association, 1971 -I 976. Reprint requests should be addressed to Dr. C. J. Glueck, General Clinical Research Center, Cincinnafi General Hospital, 234 Goodman St.. Rm. C2-3. Cincinnati, Ohio 45267. @ 1977 bv Grune & Stratton. Inc.
Metabolism,
Vol.
26,
No.
4 (April),
1977
347
GLUECK
348
ET
AL.
were assessed in II7 neonates (58 white. 59 black). Cord blood total cholesterol. high- (alpha) and low- (beta) density lipoprotein cholesterol (C-HDL. C-LDL). and triglycerides were quantitated to evaluate potential early expression 01 “genetic” racial distinctions. No significant differences were observed for total cholesterol (TC), C-HDL, C-LDL, C-HDL/C-LDL, or C-HDL/TC in comparison of black and white neonates. MATERIALS The 117 neonates were enrolled of a cord Cord
blood
blood
lipid
and
cholesterol.
AND METHODS
into the study in the consecutive
lipoprotein
C-HDL,
survey and
C-LDL,
in a cohort triglyceride
order
of 3000 were
of their
birth
as part
consecutive
live
births.4
quantitated
as previously
de-
scribed.4 There
was no known
secutively
in order
obtained.
No exclusions
bias in selection
of their
live birth,
of the neonates. provided
that
with
whites
informed
were made on the basis of perinatal
and
consent
blacks
of the
complications.
which
taken
con-
parent(s)
was
are, however.
known to elevate cord blood triglycerides.5’6
Statistical
Anal~~ses
Comparisons major groups: (Table
of the various cord blood lipids and lipoproteins all black
1). The tests of significant
method
I.’ This approach
The correlation
coefficients
the four patient
equivalent
difference
allowed
unequal numbers of observations within
all
versus all white,
male
versus
were performed
analyses
of variance
and
using the foIlowIng sex-race
using the general
to be performed
linear
interaction hypothesis.
on data composed
of
within the four patient groups.
were obtained
by pooling
the sums of squares and cross products
groups: white male. white female.
to obtaining
were made
all female,
the correlation
coefficients
black
after
male.
adjusting
and black
the data
female.
This
is
for the four groups
using the method ofcovariance.’
RESULTS
As summarized in Table I, there were no black-white or male-female differences in cord blood TC and C-HDL. Similarly, there were no black-white or male-female differences in the ratio of C-HDL/C-L.DL and the ratio of C-HDL/TC. Cord blood triglycerides were slightly elevated in black neonates as compared to whites, p = 0.02. For the entire cohort, C-HDL did not correlate with C-LDL (r = 0.002). while C-HDL correlated closely with total cholesterol (r = 0.63. p < 0.001). Table
1.
Comparison
C-HDL/C-LDL
of TC, Triglyceride and
C-HDL/TC
(TG),
in 58 White
C-HDL, and
C-LDL,
Block White
White
Block
and
the Ratios
59 Black Neonates versus
White
Block
Sex-Race
Female
Interaction
Males
Females
(N = 26)
(N = 41)
(N = 18)
TG
28i
13
29zt
16
34i
17
38i
21
5.42*
0.58
0.07
TC
71 *
15
74i
13
72zt
17
71 *
15
0.03
0.006
0.36
C-HDL
34 f
8
38 f
9
35&
12
35 *
11
0.04
0.77
0.81
C-LDL
33*
11
30*
11
35i
12
32zt
10
0.96
i .2a
0.0003
C-HDL/C-LDL
1.2 *
0.5
1.4 i
0.8
1.2 f
0.6
1.2 *
C-HDL/TC
0.5
0.1
0.5
0.1
0.5
0.1
0.5
All v&es ‘p
in mg/dl,
= 0.002.
*
mean
*
i
SD.
tdf = degrees of freedom
f
(I,
113df)t
F Ratio
F Ratio
Females
(N = 32)
M&S
F Ratio
Male versus
(l.113dfl
(1. 113df)
0.5
1.19
1.73
1.19
zb 0.1
0.18
0.91
0.32
BLACK-WHITE
SIMILARITIES
349
DISCUSSION
Black-white lipid and lipoprotein comparisons in neonates are presumably little beclouded by powerful “environmental” factors operative in adults: occupation, education, social class, smoking, weight,’ cholesterol and saturated fat intake, exercise levels,’ etc. Additionally, there is considerable evidence that most of the “genetic” dyslipoproteinemias can be expressed at birth, including familial hypercholesterolemia (elevated cord blood C-LDL’,“), familial hypobetalipoproteinemia,” and familial hyperalphalipoproteinemia.” Hence study of cord blood lipids and lipoproteins in neonates offers one potentially fruitful avenue for the exploration of possible genetic’ differences in lipoproteins in blacks and whites. At comparable TC levels there were no neonatal black-white differences in C-HDL or C-LDL, in contrast to Evans County adults,’ where blacks had higher C-HDL and whites had higher C-LDL and triglycerides, The blackwhite similarities in neonatal C-HDL and C-LDL are also in contrast to higher alphalipoprotein levels in 5514-yr-old black school children in Bogalusa, La.” The higher triglycerides in black neonates probably are accounted for by a greater black prevalence of perinatal and neonatal hypoxia and stress.s,6 Our previous studies in 1800 neonates revealed no black-white differences in cord blood TC and C-LDL.14 Within the limitations of “genicity” as expressed by cord blood lipoproteins, and particularly for C-LDL and C-HDL, there were no obvious black-white differences in our studies of neonates. Better resolution of possible black-white differences in C-LDL and C-HDL may be provided by analysis of our Princeton School Study of 6758 black and white children, ages 6-17 yr,15 where large cross-sectional samples by age, sex, and race are available. In the Princeton study,” as in Bogalusa,‘31’6 fasting plasma cholesterol was generally higher in black children, while triglycerides were generally higher in white children. We speculate that American blackwhite differences in lipids and lipoproteins’~‘3~‘5~‘6 are more likely to be predominantly “environmental.” REFERENCES I. Tyroler HA, Hames CG. Krishan I. et al: Black-white differences in serum lipids and lipoproteins in Evans County. Prev Med 4:541549, 1975 2. Glueck CJ: Alpha-lipoprotein cholesterol, beta-lipoprotein cholesterol, and longevity. Artery 2:196-198, 1976 3. Rhoads GG, Gulbrandsen CL, Kagan A: Serum lipoproteins and coronary heart disease in a population survey of Hawaii Japanese men. N Engl J Med 294:2933298, 1976 4. Tsang RC, Glueck CJ, Fallat RW, et al: Neonatal familial hypercholesterolemia. Am J Dis Child 129:83-91, 1975 5. Tsang RC, Glueck CJ: Cord blood hypertriglyceridemia. Am J Dis Child 127:78-82, 1974 6. Andersen GE, Friis-Hansen B: Neonatal
hypertriglyceridaemia. Acta Paediatr Stand 65: 3699374. 1976 7. Overall JE, Spiegel DK: Concerning least squares analysis of experimental data. Psycho] Bull 72:3l I-322, 1969 8. Ostle B: Statistics in Research (ed 2). Ames, Iowa State Univ Pr, 1963. p 442 9. Wood PD. Klein H, Lewis S. et al: Plasma lipoprotein concentrations in middle aged male runners. Circulation 50: 115. 1974 10. Tsang RC, Fallat RW, Glueck CJ: Cholesterol at birth and age I: Comparison of normal and hypercholesterolemic neonates. Pediatrics 53:458--470, 1974 I I. Glueck CJ. Tsang RC, Mellies MJ. et al: Neonatal familial hypobetalipoproteinemia. Metabolism 25:6l l--614. 1976
GLUECK
350
I?.
Glueck
al: Neonatal Clin
CJ. Gartside familial
Res 24:525A.
13. Srinivasan et
al:
from
Serum a biracial
318, 1976 14. Glueck et
al:
PM,
Tsang
RC.
et
protelnemia: births.
hyperalphalipoproteinemia.
IS.
1976 SR, Frerichs
RR,
Webber
lipoprotein
profile
community.
Circulation
in
LS,
children 54:309
Cord
Metabolism DeGroot
al: Lipids normal
limits.
et al: Serum CJ.
Neonatal
Heckman familial
F. Schoenfeld type
IL
M.
hyperlipo-
in 3.446 Circulation
cholesterol 60X. 197
I. Morrison
JA.
in school
16. Frerichh
blood 2597
Clin
children
cholesterol
children 53:X)?
from
and
Kelly
IX00
K.4.
et
1976 SR. Webber
trlplyceride
d birnclal
309. 1976
In
I
ages 6 17. Upper
Res 24:525A.
RR. Srinivasan
ET AL.
LS. levrls
communit>.
NO. 4
PRELIMINARY
Cord in
blood
117
J.
assess
for
racial
lipid
black
and
differences density low-density
Similarities in Cord Blood Lipids and Lipoproteins
Glueck, P. S. Gartside,
lipoproteins
neonates
(58
were white,
potential
C-HDL/C-LDL,
black)
to
glycerides
of
neonates
of
adult
no
the
there
were
(TC),
cholesterol
lipoprotein
Mellies, and P. M. Steiner
expression
cholesterol
lipoprotein
M.
In comparison
neonates
in total
R. C. Tsang,
quantitated 50
early
distinctions. white
1977
REPORT
Black-White C.
APRIL
cholesterol
high-
(C-HDL), (C-LDL),
or C-HDL/TC. were (p
=
black-white limits
cord blood
of
higher
0.02).
Unlike
comparisons
“genicity”
lipoproteins,
cial differences
Cord
slightly
in C-HDL,
as there
blood in
certain and
within
expressed were
C-LDL,
tri-
black
and
by
no ratotal
cholesterol.
UBSEQUENT to finding an excess of coronary artery disease in Evans County, Ga., whites,’ Tyroler et al. reported “. . . higher LDL [low-density lipoprotein] cholesterol and total triglycerides are present in whites, and higher HDL [high-density lipoprotein] cholesterol was found in blacks in an age, sex, and total serum cholesterol matched comparison.” Tyroler et al. found no race-related differences in occupation, education, social class, or smoking habits and suggested a “possible genetic origin” for the lipoprotein differences.’ Although Tyroler et al. acknowledged that the black-white differences in coronary disease were consistent with “either the atherogenicity of the higher VLDL [very-low-density lipoprotein] and LDL cholesterol and total triglycerides of white males or the protectiveness of higher HDL cholesterol in black males . . . ,” the negative coronary-risk-factor status of HDL2,3 was emphasized. In the current study, possible “genetic” black-white lipoprotein differences’
S
From the Clinical Research and Lipid Research Centers and the Department of Epidemiolog) and Biostatistirs. University of Cincinnati College of Medicine.Cincinnati. Ohio. Received&v publication September 22, 1976: Supported in part bjl GCRCgranr RR-0006X-14. A portion of this work was done during Dr. Glueck’s tenure as an established investigator of the American Heart Association, 1971 -I 976. Reprint requests should be addressed to Dr. C. J. Glueck, General Clinical Research Center, Cincinnafi General Hospital, 234 Goodman St.. Rm. C2-3. Cincinnati, Ohio 45267. @ 1977 bv Grune & Stratton. Inc.
Metabolism,
Vol.
26,
No.
4 (April),
1977
347
GLUECK
348
ET
AL.
were assessed in II7 neonates (58 white. 59 black). Cord blood total cholesterol. high- (alpha) and low- (beta) density lipoprotein cholesterol (C-HDL. C-LDL). and triglycerides were quantitated to evaluate potential early expression 01 “genetic” racial distinctions. No significant differences were observed for total cholesterol (TC), C-HDL, C-LDL, C-HDL/C-LDL, or C-HDL/TC in comparison of black and white neonates. MATERIALS The 117 neonates were enrolled of a cord Cord
blood
blood
lipid
and
cholesterol.
AND METHODS
into the study in the consecutive
lipoprotein
C-HDL,
survey and
C-LDL,
in a cohort triglyceride
order
of 3000 were
of their
birth
as part
consecutive
live
births.4
quantitated
as previously
de-
scribed.4 There
was no known
secutively
in order
obtained.
No exclusions
bias in selection
of their
live birth,
of the neonates. provided
that
with
whites
informed
were made on the basis of perinatal
and
consent
blacks
of the
complications.
which
taken
con-
parent(s)
was
are, however.
known to elevate cord blood triglycerides.5’6
Statistical
Anal~~ses
Comparisons major groups: (Table
of the various cord blood lipids and lipoproteins all black
1). The tests of significant
method
I.’ This approach
The correlation
coefficients
the four patient
equivalent
difference
allowed
unequal numbers of observations within
all
versus all white,
male
versus
were performed
analyses
of variance
and
using the foIlowIng sex-race
using the general
to be performed
linear
interaction hypothesis.
on data composed
of
within the four patient groups.
were obtained
by pooling
the sums of squares and cross products
groups: white male. white female.
to obtaining
were made
all female,
the correlation
coefficients
black
after
male.
adjusting
and black
the data
female.
This
is
for the four groups
using the method ofcovariance.’
RESULTS
As summarized in Table I, there were no black-white or male-female differences in cord blood TC and C-HDL. Similarly, there were no black-white or male-female differences in the ratio of C-HDL/C-L.DL and the ratio of C-HDL/TC. Cord blood triglycerides were slightly elevated in black neonates as compared to whites, p = 0.02. For the entire cohort, C-HDL did not correlate with C-LDL (r = 0.002). while C-HDL correlated closely with total cholesterol (r = 0.63. p < 0.001). Table
1.
Comparison
C-HDL/C-LDL
of TC, Triglyceride and
C-HDL/TC
(TG),
in 58 White
C-HDL, and
C-LDL,
Block White
White
Block
and
the Ratios
59 Black Neonates versus
White
Block
Sex-Race
Female
Interaction
Males
Females
(N = 26)
(N = 41)
(N = 18)
TG
28i
13
29zt
16
34i
17
38i
21
5.42*
0.58
0.07
TC
71 *
15
74i
13
72zt
17
71 *
15
0.03
0.006
0.36
C-HDL
34 f
8
38 f
9
35&
12
35 *
11
0.04
0.77
0.81
C-LDL
33*
11
30*
11
35i
12
32zt
10
0.96
i .2a
0.0003
C-HDL/C-LDL
1.2 *
0.5
1.4 i
0.8
1.2 f
0.6
1.2 *
C-HDL/TC
0.5
0.1
0.5
0.1
0.5
0.1
0.5
All v&es ‘p
in mg/dl,
= 0.002.
*
mean
*
i
SD.
tdf = degrees of freedom
f
(I,
113df)t
F Ratio
F Ratio
Females
(N = 32)
M&S
F Ratio
Male versus
(l.113dfl
(1. 113df)
0.5
1.19
1.73
1.19
zb 0.1
0.18
0.91
0.32
BLACK-WHITE
SIMILARITIES
349
DISCUSSION
Black-white lipid and lipoprotein comparisons in neonates are presumably little beclouded by powerful “environmental” factors operative in adults: occupation, education, social class, smoking, weight,’ cholesterol and saturated fat intake, exercise levels,’ etc. Additionally, there is considerable evidence that most of the “genetic” dyslipoproteinemias can be expressed at birth, including familial hypercholesterolemia (elevated cord blood C-LDL’,“), familial hypobetalipoproteinemia,” and familial hyperalphalipoproteinemia.” Hence study of cord blood lipids and lipoproteins in neonates offers one potentially fruitful avenue for the exploration of possible genetic’ differences in lipoproteins in blacks and whites. At comparable TC levels there were no neonatal black-white differences in C-HDL or C-LDL, in contrast to Evans County adults,’ where blacks had higher C-HDL and whites had higher C-LDL and triglycerides, The blackwhite similarities in neonatal C-HDL and C-LDL are also in contrast to higher alphalipoprotein levels in 5514-yr-old black school children in Bogalusa, La.” The higher triglycerides in black neonates probably are accounted for by a greater black prevalence of perinatal and neonatal hypoxia and stress.s,6 Our previous studies in 1800 neonates revealed no black-white differences in cord blood TC and C-LDL.14 Within the limitations of “genicity” as expressed by cord blood lipoproteins, and particularly for C-LDL and C-HDL, there were no obvious black-white differences in our studies of neonates. Better resolution of possible black-white differences in C-LDL and C-HDL may be provided by analysis of our Princeton School Study of 6758 black and white children, ages 6-17 yr,15 where large cross-sectional samples by age, sex, and race are available. In the Princeton study,” as in Bogalusa,‘31’6 fasting plasma cholesterol was generally higher in black children, while triglycerides were generally higher in white children. We speculate that American blackwhite differences in lipids and lipoproteins’~‘3~‘5~‘6 are more likely to be predominantly “environmental.” REFERENCES I. Tyroler HA, Hames CG. Krishan I. et al: Black-white differences in serum lipids and lipoproteins in Evans County. Prev Med 4:541549, 1975 2. Glueck CJ: Alpha-lipoprotein cholesterol, beta-lipoprotein cholesterol, and longevity. Artery 2:196-198, 1976 3. Rhoads GG, Gulbrandsen CL, Kagan A: Serum lipoproteins and coronary heart disease in a population survey of Hawaii Japanese men. N Engl J Med 294:2933298, 1976 4. Tsang RC, Glueck CJ, Fallat RW, et al: Neonatal familial hypercholesterolemia. Am J Dis Child 129:83-91, 1975 5. Tsang RC, Glueck CJ: Cord blood hypertriglyceridemia. Am J Dis Child 127:78-82, 1974 6. Andersen GE, Friis-Hansen B: Neonatal
hypertriglyceridaemia. Acta Paediatr Stand 65: 3699374. 1976 7. Overall JE, Spiegel DK: Concerning least squares analysis of experimental data. Psycho] Bull 72:3l I-322, 1969 8. Ostle B: Statistics in Research (ed 2). Ames, Iowa State Univ Pr, 1963. p 442 9. Wood PD. Klein H, Lewis S. et al: Plasma lipoprotein concentrations in middle aged male runners. Circulation 50: 115. 1974 10. Tsang RC, Fallat RW, Glueck CJ: Cholesterol at birth and age I: Comparison of normal and hypercholesterolemic neonates. Pediatrics 53:458--470, 1974 I I. Glueck CJ. Tsang RC, Mellies MJ. et al: Neonatal familial hypobetalipoproteinemia. Metabolism 25:6l l--614. 1976
GLUECK
350
I?.
Glueck
al: Neonatal Clin
CJ. Gartside familial
Res 24:525A.
13. Srinivasan et
al:
from
Serum a biracial
318, 1976 14. Glueck et
al:
PM,
Tsang
RC.
et
protelnemia: births.
hyperalphalipoproteinemia.
IS.
1976 SR, Frerichs
RR,
Webber
lipoprotein
profile
community.
Circulation
in
LS,
children 54:309
Cord
Metabolism DeGroot
al: Lipids normal
limits.
et al: Serum CJ.
Neonatal
Heckman familial
F. Schoenfeld type
IL
M.
hyperlipo-
in 3.446 Circulation
cholesterol 60X. 197
I. Morrison
JA.
in school
16. Frerichh
blood 2597
Clin
children
cholesterol
children 53:X)?
from
and
Kelly
IX00
K.4.
et
1976 SR. Webber
trlplyceride
d birnclal
309. 1976
In
I
ages 6 17. Upper
Res 24:525A.
RR. Srinivasan
ET AL.
LS. levrls
communit>.
