Atherosclerosis and Lipoproteins |
From the Lipid Research Center (J.-P.D., C.C., J.B.), CHUQ Research Center, CHUL Pavilion, Sainte-Foy, Québec, Canada; the Division of Kinesiology (J.-P.D., J.G.), Laval University School of Medecine, Sainte-Foy, Québec, Canada; the School of Kinesiology and Leisure Studies (A.S.L.), University of Minnesota, Minneapolis; the Division of Biostatistics (D.C.R.), Washington University Medical School, St Louis, Mo; the Department of Kinesiology (J.S.S.), Indiana University, Bloomington; the Department of Health and Kinesiology (J.H.W.) Texas A&M University, College Station; and the Pennington Biomedical Research Center (C.B.), Louisiana State University, Baton Rouge.
Correspondence to Jean-Pierre Després, PhD, Scientific Director and Professor, Lipid Research Center, CHUQ Research Center, CHUL Pavilion, 2705, boulevard Laurier, Room TR-93, Sainte-Foy, Québec, Canada G1V 4G2. E-mail Jean-Pierre.Despres{at}crchul.ulaval.ca
| Abstract |
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Key Words: race sex visceral adipose tissue lipase activities lipoproteins
| Introduction |
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In addition, lipase activities measured in postheparin plasma, ie, postheparin lipoprotein lipase (PH-LPL) and postheparin hepatic lipase (PH-HL), have been shown in several studies to be important correlates of plasma HDL cholesterol levels.11 12 13 However, their contribution to the black-white difference in plasma HDL cholesterol levels is not known. Therefore, we have measured body composition, visceral AT accumulation, plasma lipoprotein levels, and PH-LPL and PH-HL activities in a sample of 723 subjects (247 white men, 240 white women, 93 black men, and 143 black women). Potential race differences in the interrelationships among these variables were examined.
| Methods |
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65 years)
and at least 3 adult offspring (aged
17 years). The present study
describes the results of baseline data from 723 subjects studied.
Subjects were healthy and sedentary and met a number of inclusion and
exclusion criteria.14 The study protocol had been
previously approved by the Institutional Review Board at each of the 4
clinical centers. Informed consent was obtained from each
subject.
Anthropometric and Body Composition Measurements
Body weight, height, and waist and hip circumferences were
measured according to standardized procedures,15 and the
waist-to-hip ratio was calculated. Body density was measured by the
hydrostatic weighing technique.16 The mean of the highest
3 (of 10) measurements was used in the calculation of percent body fat
from body density by using the equation of Siri.17 Fat
mass was obtained by multiplying body weight by percent body fat. These
measurements have been shown to be highly reproducible, with no
difference between clinical centers or drift over
time.18
Computed Tomography
Visceral AT accumulation was assessed by computed tomography
with the use of previously described procedures.19 20
Briefly, each subject was examined in the supine position with both
arms stretched above the head. The scan was performed at the abdominal
level (between L4 and L5 vertebrae) by use of an abdominal scout
radiograph to standardize the position of the scan to the nearest
millimeter. Total AT area was calculated by delineating the abdominal
scan with a graph pen and then computing the AT surface with an
attenuation range of -190 to -30 Hounsfield units.19 20 21
The abdominal visceral AT area was measured by drawing a line within
the muscle wall surrounding the abdominal cavity. The abdominal
subcutaneous AT area was calculated by subtracting the visceral AT area
from the total abdominal AT area.
Plasma Lipid, Lipoprotein, and Apolipoprotein Measurements
Blood sampling was achieved in subjects after a 12-hour fast.
Cholesterol and triglyceride (TG) levels were
determined in plasma and in lipoprotein fractions by enzymatic methods
with a Technicon RA-500 analyzer (Bayer Corp
Inc).22 Plasma VLDL (density <1.006 g/mL) was isolated by
ultracentrifugation, and the HDL fraction was obtained
after precipitation of LDL in the infranatant (density >1.006 g/mL)
with heparin and MnCl2.23 The
cholesterol and TG contents of the infranatant fraction
were measured before and after the precipitation step. ApoB
concentration was measured in plasma by the rocket
immunoelectrophoretic method of Laurell,24 as previously
described.25 The lyophilized serum standards for
apolipoprotein measurements were prepared in our laboratory and
calibrated with reference standards obtained from the Centers for
Disease Control. The cholesterol content of
HDL2 and HDL3 subfractions
was also determined after further precipitation of
HDL2 with dextran sulfate.26
Reproducibility of all lipid-lipoprotein measurements has been examined
and found to be excellent.27
Postheparin Plasma Lipase Activities
LPL and HL activities were also measured on one occasion in
subjects after a 12-hour overnight fast, 10 minutes after an
intravenous injection of heparin (60 IU/kg body wt). The
postheparin plasma lipase activities (PHLAs) were measured
by using a modification of the method of Nilsson-Ehle and
Ekman,28 as previously described.29 The 2
lipolytic enzyme activities were expressed as nanomoles of oleic
acid released per milliliter of plasma per minute. These measures have
also been found to be highly reproducible.27
Statistical Analysis
Values are expressed as mean±SD. Pearson product-moment
correlation coefficients were used to quantify the relationships among
variables. General linear model analyses were used to test
the differences between men and women as well as between sex and race.
Multiple regression analyses were also performed to estimate
the independent contribution of age, sex, race, total body fat mass,
visceral AT, and PH-LPL and PH-HL activities to the variations in
fasting plasma TG, HDL cholesterol, and apo B levels and in
the ratio of total cholesterol to HDL
cholesterol.
| Results |
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These differences in adiposity and in AT distribution were accompanied
by sex differences in the lipoprotein profile (Table 2
). Compared with white women, white men
had a less favorable metabolic risk profile, as revealed by
increased fasting plasma TG and apoB levels as well as by a higher
ratio of total cholesterol to HDL cholesterol.
In addition, compared with white women, white men showed lower
concentrations of HDL, HDL2, and of
HDL3 cholesterol. Similar
metabolic differences according to sex were noted in
blacks, with the exception of HDL3
cholesterol concentrations, which were comparable in black
men and black women. In whites, women were characterized by lower PH-HL
and higher PH-LPL activities. In blacks, no difference was noted in
plasma PH-LPL activity, but women showed a lower plasma PH-HL activity.
In both ethnic groups, women had a lower HL-to-LPL ratio than did
men.
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Effect of Race
When race-related differences in body fatness and AT distribution
in men were examined (Table 1
), we found that compared with
black men, white men were characterized by an increased visceral AT
deposition, despite the fact that both groups had similar body mass
index and body fat mass values. In women, race was mostly associated
with differences in overall adiposity indices: compared with white
women, black women were characterized by increased body weight, body
mass index, percentage of body fat, and fat mass. This elevated
adiposity in black women also resulted in an increased waist girth and
higher levels of subcutaneous AT compared with the values in white
women. Thus, black women were more obese than white women. However, the
2 groups of women had similar levels of visceral AT despite the higher
overall adiposity of black women, suggesting that white women were more
prone to visceral AT deposition than were black women.
When the plasma lipoprotein profile was compared between the 2 ethnic
groups (Table 2
), we found that black men and women were
generally characterized by a more favorable profile than were white men
and women. Indeed, compared with black men, white men showed increased
TG and apoB concentrations as well as a higher ratio of total
cholesterol to HDL cholesterol. Compared with
black men, white men also showed lower HDL cholesterol
concentrations. Furthermore, compared with white women, black women had
lower cholesterol, TG, and apoB levels. Compared with black
men, white men showed reduced PH-LPL and higher PH-HL activities,
whereas compared with white women, black women were characterized by
higher PH-LPL and lower PH-HL activities. These differences resulted in
a higher HL-to-LPL ratio in whites compared with blacks.
Figure 1
illustrates the relationships of
body fat mass to abdominal visceral and subcutaneous AT accumulation in
men and women of both ethnic origins. Irrespective of race, body fat
mass was positively correlated with visceral and subcutaneous AT
accumulation. However, although the relationship of subcutaneous AT to
total body fat mass was similar across race groups, there were
differences in the relationships of visceral AT to body fat mass.
Indeed, black men and black women had, for a given amount of total body
fat mass, less visceral AT than did whites.
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The detrimental effect of adiposity on plasma lipoprotein levels is
shown in Figure 2
. Increased adiposity,
expressed as either total body fat or visceral AT accumulation, was
associated with a decrease in HDL cholesterol
concentrations in all subgroups of subjects. Furthermore, in the whole
cohort, visceral AT also showed significant positive correlations with
TG (r=0.52, P<0.0001) and apoB
(r=0.55, P<0.0001) levels as well as with the
ratio of total cholesterol to HDL cholesterol
(r=0.56, P<0.0001). These relationships were
also noted with total body fat mass, although associations were of
lower magnitude (r
0.36) than with visceral AT
accumulation.
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We have also examined the potential associations between visceral AT
accumulation and PH-LPL as well as PH-HL activity (Figure 3
). In women, we found that visceral AT
accumulation was positively associated with PH-HL activity regardless
of ethnicity. As opposed to what was found in women, visceral AT
accumulation was not correlated with PH-HL in either black or white
men. In all groups, visceral AT was not correlated with PH-LPL
activity.
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Finally, we have also attempted to quantify the independent
contributions of age, sex, race, body fat mass, visceral AT
accumulation, and PHLA to the variance of TG, apoB, HDL
cholesterol, and the ratio of total cholesterol
to HDL cholesterol (Table 3
).
PH-LPL activity was the best predictor of fasting HDL
cholesterol concentrations. On the other hand, visceral AT
accumulation was by far the best correlate of the variations in TG,
apoB, and the ratio of total cholesterol to HDL
cholesterol. The important finding of these
analyses was that after control for body fatness, visceral AT
accumulation, and PH-LPL activity, ethnicity, per se, had a trivial
contribution to the variance of metabolic risk
variables. Indeed, after control for the morphometric and
metabolic variables examined in the present study,
race explained only 1.6% and 0.5% of the variance in fasting plasma
TG and apoB concentrations, respectively.
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| Discussion |
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As expected, compared with men, women showed a more favorable metabolic risk profile. Previous studies had reported sex differences in fasting plasma lipoprotein-lipid concentrations, including lower TG and higher HDL cholesterol levels in women than in men.33 34 In the present study, compared with white women, white men were characterized by higher plasma TG and apoB concentrations as well as by lower HDL cholesterol levels. These differences were also noted in blacks. However, results of our multivariate analyses revealed that with the exception of plasma HDL cholesterol levels, which were characterized by a significant sex effect, differences in the plasma lipid profile between men and women were largely explained by differences in visceral AT and PH-LPL activity. In addition to the variation in lipoprotein-lipid levels between men and women, a significant sex difference in PHLA was also found, a finding that is concordant with several,35 36 37 38 but not all,39 40 previous reports. In the present study, lower PH-HL activity was found in women compared with men. However, higher PH-LPL activity in women was noted only in whites.
Effect of Race
Race differences have been reported in body composition and AT
distribution. At any level of total body fat, compared with black
subjects, white subjects have been shown to be characterized by a
greater visceral AT accumulation.6 7 8 Results of
regression analyses conducted in the present study are
concordant with these earlier findings. For any level of total body
fat, compared with blacks, whites were characterized by a higher
accumulation of visceral AT, supporting the notion that whites are more
prone to visceral obesity than are blacks. In contrast, we found no
race difference in the relationship of subcutaneous fat to total body
fat mass. Thus, the present study supports the view that the
cross-sectional area of abdominal subcutaneous fat measured by computed
tomography at L4-L5 is a good predictor of total body fat
content32 and that there does not appear to be major
ethnic differences in such a relationship. This issue will have to be
examined in other ethnic groups, such as Hispanic and Asian
populations.
The main objective of the present study was to verify whether differences in body composition and AT distribution as well as in the activity of enzymes relevant to lipoprotein metabolism could explain the generally more favorable lipoprotein profile found in black than in white individuals. Indeed, compared with white individuals, black individuals have been characterized by lower fasting TG as well as higher HDL cholesterol concentrations.6 7 10 Such differences were also found in the present study, inasmuch as white subjects had higher fasting TG and apoB levels than did black subjects. This race-related difference was observed along with the expected sex difference in plasma lipoprotein levels, with women having a more favorable profile than men.
In both sexes, blacks showed a significantly higher PH-LPL activity than did whites. Compared with white individuals, black individuals also showed reduced PH-HL activity, and such ethnic differences were found in both sexes, a finding that is concordant with previous observations.41 Such a difference in PHLA is of importance because it may contribute to the more favorable plasma lipoprotein-lipid profile of black individuals compared with white individuals. Thus, the present study found a stepwise increase in TG and apoB levels as well as in the ratio of total cholesterol to HDL cholesterol as follows for the various groups: black women (lowest values), white women, black men, and then white men (highest values); this stepwise increase appeared to parallel the gradient in visceral AT and the HL-to-LPL ratio among these 4 groups. Results from our multivariate analyses also revealed that visceral AT was the critical correlate of plasma TG, apoB, and the ratio of total cholesterol to HDL cholesterol in the present study. Thus, our results suggest that the more favorable metabolic risk profile found in blacks than in whites could be due to the fact that white subjects are more prone to visceral AT accumulation than are black subjects. Furthermore, the higher plasma HDL cholesterol levels found in blacks than in whites appear to be explained, at least to a significant extent, by the higher PH-LPL activity in blacks. This effect of ethnicity on PH-LPL activity is concordant with recent findings.42
In summary, results of the present study indicate that the more favorable lipoprotein profile generally found in abdominally obese black individuals could be explained, at least to a significant extent, by their lower visceral AT accumulation and by their higher PH-LPL activity compared with those values in abdominally obese white individuals.
| Acknowledgments |
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Received January 31, 2000; accepted March 29, 2000.
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