Upload
tommi
View
212
Download
0
Embed Size (px)
Citation preview
ORIGINAL ARTICLE
Postpartum Weight Retention is Associated with Elevated Ratioof Oxidized LDL Lipids to HDL-Cholesterol
Jatta Puhkala • Riitta Luoto • Markku Ahotupa •
Jani Raitanen • Tommi Vasankari
Received: 31 July 2013 / Accepted: 13 September 2013 / Published online: 12 October 2013
� AOCS 2013
Abstract Oxidized LDL lipids (ox-LDL) are associated
with lifestyle diseases such as cardiovascular diseases,
metabolic syndrome and type 2 diabetes. The present study
investigated how postpartum weight retention effects on
ox-LDL and serum lipids. The study is a nested compara-
tive research of a cluster-randomized controlled trial,
NELLI (lifestyle and counselling during pregnancy). Dur-
ing early pregnancy (8–12 weeks) and 1 year postpartum,
141 women participated in measurements for determining
of plasma lipids: total cholesterol (T-C), LDL-cholesterol
(LDL-C), HDL-cholesterol (HDL-C), triacylglycerols
(TAG) and ox-LDL. Subjects were stratified into tertiles
(weight loss, unaltered weight and weight gain groups)
based on their weight change from baseline to follow-up.
Ox-LDL was determined by baseline level of conjugated
dienes in LDL lipids. Among the group of weight gainers,
concentration of TAG reduced less (-0.14 vs. -0.33,
p = 0.002), HDL-C reduced more (-0.31 vs. -0.16,
p = 0.003) and ox-LDL/HDL-C ratio increased (3.0 vs.
-0.2, p = 0.003) when compared to group of weight loss.
Both T-C and LDL-C elevated more (0.14 vs. -0.21,
p = 0.008; 0.31 vs. 0.07, p = 0.015) and TAG and ox-
LDL reduced less (-0.33 vs. 0.20, p = 0.033; -3.33 vs.
-0.68, p = 0.026) in unaltered weight group compared to
weight loss group. The women who gained weight devel-
oped higher TAG and ox-LDL/HDL-C ratio as compared
to those who lost weight. Postpartum weight retention of
3.4 kg or more is associated with atherogenic lipid profile.
Keywords Oxidized LDL to HDL ratio �Postpartum � Plasma lipids � Weight retention �Weight loss
Abbreviations
BMI Body mass index
GDM Gestational diabetes
HDL-C HDL cholesterol
LDL-C LDL cholesterol
NELLI Name of the study, lifestyle and counselling
during pregnancy
OGTT Oral glucose tolerance test
ox-LDL Oxidized LDL
T-C Total cholesterol
TAG Triacylglycerols
Introduction
The high levels of total cholesterol (T-C) and low-density
lipoprotein cholesterol (LDL-C), and low levels of high-
density lipoprotein cholesterol (HDL-C) are well-known
risk factors for atherosclerosis and cardiovascular diseases
[1]. In certain circumstances, LDL is oxidatively modified,
which has several proatherogenic and proinflammatory
effects in arterial wall [2]. Oxidized LDL (ox-LDL) is
scavenged by macrophages in endothelium, which
J. Puhkala (&) � R. Luoto � J. Raitanen � T. Vasankari
UKK Institute for Health Promotion Research, Box 30,
33501 Tampere, Finland
e-mail: [email protected]
R. Luoto � T. Vasankari
The National Institute for Health and Welfare, Helsinki, Finland
M. Ahotupa
Department of Physiology, University of Turku, Turku, Finland
J. Raitanen
School of Health Sciences, University of Tampere, Tampere,
Finland
123
Lipids (2013) 48:1227–1235
DOI 10.1007/s11745-013-3852-9
accelerates the pathogenesis of atherosclerosis [3–5]. Ele-
vated ox-LDL level is associated with atherosclerosis [6].
Ox-LDL accumulates excessively into the arterial wall in
an unregulated fashion, whereas native LDL has no similar
properties [7]. HDL may protect LDL from oxidization and
attenuate the effects of ox-LDL in endothelium [8, 9].
HDL-C has multiple antiatherogenic and antioxidative
features [8–10]. Previous studies have shown that the ratio
of ox-LDL to HDL-C is a potential biomarker for increased
risk of coronary artery disease and all-cause mortality
[11, 12].
Being overweight is associated with many diseases,
including cardiovascular diseases [13], and it is also con-
nected to elevated plasma ox-LDL as well as decreased
HDL-C levels [14]. Obese individuals often tend to have
co-morbidities like metabolic syndrome and type 2 diabe-
tes that also are associated with same kind of alterations of
lipid profile [15]. There are only a few studies about effect
of weight change on ox-LDL levels. In a previous study,
the oxidation of LDL was reduced after weight reduction in
obese premenopausal women [16]. In obese middle-aged
men, ox-LDL was reduced after weight reduction and also
remained reduced among those who could maintain the
weight loss for 2 years [17]. Many other studies instead
have shown that weight reduction positively affects plasma
lipids like T-C, LDL-C, HDL-C and TAG [18, 19].
Pregnancy plays an important role in development of
excessive weight among many women. The magnitude of
parity-associated gained weight is around 0.5–3.2 kg,
estimated as 7 % increase of obesity risk with each addi-
tional child [20–22]. Variation in weight retention is large
and some women may retain over 17 kg [21]. The
triggering effect has turned into a cumulative effect among
multiparous women with at least three children, who can be
considered a special risk group. In Finland, 10-year trends
in obesity by parity have been associated with visceral
obesity [23].
We have earlier reported the main results of the lifestyle
trial, showing that intervention was effective in producing
positive changes in diet and physical activity [24]. The aim
of the current study is to perform an analysis of the trial
and follow-up data in order to investigate how postpartum
weight retention effects on concentration of ox-LDL and
serum conventional lipids.
Materials and Methods
The study is a nested comparative research of a gestational
diabetes (GDM) preventive trial, NELLI (lifestyle and
counselling during pregnancy) [24]. A more detailed
description of the design and methods has been reported
previously [25]. The primary aim of the trial was to prevent
GDM among pregnant women who were assessed in early
pregnancy to have increased risk for GDM. Women were
eligible if they had at least one of the following GDM risk
factors: age C40 years, pre-pregnancy body mass index
(BMI) C25 kg/m2, GDM or any sign of glucose intolerance
or a macrosomic baby (C4,500 g) in any previous preg-
nancy, or diabetes in first or second grade relatives. The
study was conducted in primary health care maternity
clinics in 2007–2009. The intervention included structured
individual counselling on weight gain, diet and physical
activity by public health nurses during five routine visits to
Table 1 Baseline (pre-
pregnancy or 8–12 weeks’
gestation) characteristics of
women by weight change from
baseline to 1 year follow-up
Means and standard deviations
or frequencies (and proportions)
of participants (n = 141) and
p values for differences between
the groups (one-way ANOVA
or v2 test)a n = 137b n = 139
Weight loss
group -16.6
to -0.5 kg
(n = 45)
Unaltered weight
group -0.4
to 3.4 kg
(n = 46)
Weight gain
group 3.5
to 18.0 kg
(n = 50)
p value
Age, years 31.6 ± 5.2 29.9 ± 4.9 29.8 ± 4.6 0.150
Height, cm 167.3 ± 6.8 167.0 ± 6.8 165.6 ± 5.4 0.365
Parity
0 13 (29) 13 (29) 23 (48) 0.140
1 24 (53) 24 (53) 16 (33)
C2 8 (18) 8 (18) 9 (19)
Educationa
University degree 16 (36) 13 (29) 11 (23) 0.456
Polytechnic education 15 (34) 22 (49) 21 (44)
Basic or secondary education 13 (30) 10 (22) 16 (33)
Smoking half a year before pregnancyb
No 37 (82) 32 (71) 36 (74) 0.767
Occasionally 5 (11) 7 (16) 7 (14)
Frequently 3 (7) 6 (13) 6 (12)
1228 Lipids (2013) 48:1227–1235
123
maternity clinics. The women in the control clinics
received usual maternal care including some dietary and
physical activity advice.
A total of 604 pregnant women participated in baseline
assessments (8–12 weeks’ gestation), of whom 442 (69 %)
were eligible for the randomized intervention study
(intensified counselling or usual care). The rest, 198
(31 %), were excluded, most of them (88 %) due to diag-
nosis of GDM [26] in early pregnancy. A total of 464
women participated in follow-up assessments 1 year post-
partum. Women with new pregnancies were excluded from
follow-up measurements. Current data consisted of results
from 141 women, who had information available for both
the lipids and weight at early pregnancy and 1 year post-
partum. Of these, 50 (36 %) of them had been in the ori-
ginal intensified counselling group, 59 (41 %) in the usual
care and 32 (23 %) had abnormal OGTT at baseline. The
participants with abnormal OGTT at baseline had got usual
care of GDM. For the analysis of changes in plasma lipids
according to weight change, the 141 women were stratified
into tertiles: subjects in first tertile, ‘‘weight loss group’’
(n = 45) reduced weight more than 0.4 kg; subjects in
second tertile, ‘‘unaltered weight group’’ (n = 46) reduced
weight max 0.4 kg or gained max 3.4 kg and subjects in
third tertile, ‘‘weight gain group’’ (n = 50) gained weight
more than 3.4 kg between the baseline (8–12 weeks’ ges-
tation) and follow-up (1 year postpartum) measurements.
The number of women of the original intensified counsel-
ling group was 15 in ‘‘weight loss group’’, 20 in ‘‘unaltered
weight group’’ and 15 in ‘‘weight gain group’’. The cor-
responding numbers of usual care group were 20, 14 and 23
and of abnormal OGTT group 9, 11 and 12.
Information on maternal measurements was obtained
from the standard maternity cards. Height was measured at
the first maternity care visit (8–12 weeks’ gestation) and
weight was measured at each maternity care visit and
1 year postpartum. Because 23 % of weight measurements
at first visit were missing, self-reported pre-pregnancy
weight was used as the baseline weight. Blood specimens
were taken after 12-h fast. For lipid analyses venous blood
was drawn into EDTA tubes. Plasma samples were stored
frozen at -80 �C until analyzed. T-C, HDL-C and TAG
concentrations were measured with enzymatic assays using
Roche Cobas Mira Plus analyzer. All analyses were made
in duplicate.
Assay of ox-LDL was based on analysis of oxidized
lipids in isolated LDL [27, 28]. LDL was isolated by pre-
cipitation with buffered heparin. The isolation procedure
was validated for the purpose, and did not affect the level
of oxidized lipids [28]. Lipids were extracted from isolated
LDL by chloroform–methanol, dried under nitrogen and
redissolved in cyclohexane. The amount of peroxidized
lipids in LDL was assessed spectrophotometrically at
234 nm. Validation studies for the assay have ruled out
interference by nonspecific substances, and shown that the
assay is a measure of oxidative modifications found in all
LDL lipid classes. The coefficient of variation (CV) for
within-assay precision for determination of oxidized LDL
lipids (ox-LDL) was 4.4 %, and the CV for the between-
assay precision was 4.5 %. The isolated LDL fraction was
used for direct measurement of LDL-cholesterol (LDL-C)
(CHOD-PAP method).
Background characteristics and descriptive information
are reported as means and standard deviations (SDs) or
frequencies and proportions. The differences between ter-
tiles of weight change at baseline were tested by variance
analysis and chi-square test. Unadjusted and adjusted linear
regression models were constructed to estimate the asso-
ciation between weight change tertiles and changes in lipid
Fig. 1 Correlation between weight change and change in a LDL
cholesterol and b HDL cholesterol from 8 to 12 weeks’ gestation to
1 year postpartum (n = 140–141)
Lipids (2013) 48:1227–1235 1229
123
outcomes from baseline to follow-up. In the adjusted
analyses we controlled for baseline lipid level, maternal
age, BMI, parity and smoking status. Normality of distri-
bution of outcome variables was tested using Kolmogorov–
Smirnov test. Results were considered statistically signifi-
cant if the p-values were \0.05. IBM SPSS Statistics
(version 20) were used to perform all analyses.
Results
Background Characteristics of the Participants
(Table 1)
There were no significant differences in any variable at
the baseline data between the three groups. The mean age
of all subjects at 8–12 weeks’ gestation was 30.4 years.
One-third of the women had no previous deliveries. One-
fourth were smoking occasionally or frequently before
pregnancy.
The Changes in Plasma Lipids Associated with Weight
Change
Figures 1, 2 and 3 show the correlations between change in
weight and change in plasma lipids from 8 to 12 weeks’
gestation to 1 year postpartum. The figures demonstrate
that weight gain correlates slightly with TAG (R = 0.27,
p = 0.001), ox-LDL (R = 0.17, p = 0.046), and ox-LDL/
HDL-C ratio (R = 0.25, p = 0.003) and conversely with
HDL-C (R = -0.23, p = 0.008). There were no correla-
tions between weight change and the change of T-C
(R = 0.07, p = 0.47), LDL-C (R = 0.13, p = 0.13) or ox-
LDL/LDL-C ratio (R = 0.07, p = 0.43).
The Changes in Plasma Lipids According to Tertiles
of Weight Change
At baseline, the mean BMI was 26.7 kg/m2 and at follow-up
27.4 kg/m2 (Table 2). The proportion of being overweight
or obese at 1 year postpartum was the same as at baseline,
64.5 %. The mean change from weight before pregnancy to
weight at 1 year postpartum was quite moderate, ?1.6 kg,
but it varied from -16.1 to ?18.0 kg. The changes in lipids
from 8 to 12 weeks’ gestation to 1 year postpartum were
less advantageous in weight gain group than in weight loss
group. According to linear regression model, the concen-
tration of TAG reduced less (-0.14, vs. -0.33, p = 0.004),
Fig. 2 Correlation between weight change and change in a triacyl-
glycerols and b oxidized LDL from 8 to 12 weeks’ gestation to 1 year
postpartum (n = 140–141)
Fig. 3 Correlation between weight change and change in oxidized
LDL/HDL cholesterol ratio from 8 to 12 weeks’ gestation to 1 year
postpartum (n = 140)
1230 Lipids (2013) 48:1227–1235
123
HDL-C reduced more (-0.31, vs. -0.16, p = 0.003), and
the ox-LDL/HDL-C ratio elevated (3.0 vs. -0.2,
p = 0.007) in weight gain group compared to the weight
loss group, when adjusted by only baseline lipid level.
These differences persisted in all variables after adjusting
the results with maternal age, BMI, parity and smoking
(Figs. 4, 5, 6, 7). Between the weight loss and the unaltered
weight groups, the only difference was T-C and LDL-C,
which both elevated more in the unaltered weight group
(T-C: 3.0 % vs. -4.4 %, p = 0.007; LDL-C: 14.3 % vs.
3.2 %, p = 0.010, baseline level as a covariate). When
results were adjusted also by baseline level, maternal age,
BMI and smoking, the differences were seen in T-C, LDL-
C, TAG and ox-LDL between the weight loss and the
unaltered weight groups.Ta
ble
2M
ean
san
dst
and
ard
dev
iati
on
so
fw
eig
ht,
bo
dy
mas
sin
dex
(BM
I)an
dp
lasm
ali
pid
sac
cord
ing
tote
rtil
eso
fw
eig
ht
chan
ge
atb
asel
ine
(pre
-pre
gn
ancy
or
8–
12
wee
ks’
ges
tati
on
)an
dat
foll
ow
-up
(1y
ear
po
stp
artu
m)
Wei
gh
tlo
ssg
rou
p-
16
.1to
-0
.5k
g(n
=4
5)
Un
alte
red
wei
gh
tg
rou
p-
0.4
to
3.4
kg
(n=
46
)
Wei
gh
tg
ain
gro
up
3.5
to
18
.0k
g(n
=5
0)
pv
alu
e
Bas
elin
eF
oll
ow
-up
Bas
elin
eF
oll
ow
-up
Bas
elin
eF
oll
ow
-up
Dif
fere
nce
bet
wee
nth
e
gro
ups
at
bas
elin
e
Dif
fere
nce
inch
ang
e
bet
wee
nw
eig
ht
loss
and
un
alte
red
wei
gh
tg
rou
ps
Dif
fere
nce
inch
ang
e
bet
wee
nw
eig
ht
loss
and
wei
gh
tg
ain
gro
up
s
Wei
gh
t,k
g7
6.2
±1
5.4
72
.3±
14
.97
1.5
±1
3.6
72
.7±
14
.97
5.0
±1
3.6
82
.1±
15
.2N
S\
0.0
00
1\
0.0
00
1
BM
I,k
g/m
22
7.1
±4
.82
5.8
±4
.82
5.6
±4
.02
5.9
±3
.42
7.3
±4
.42
9.9
±4
.8N
S\
0.0
00
1\
0.0
00
1
To
tal
cho
lest
ero
l,m
mo
l/l
4.7
±0
.64
.51
±0
.83
4.6
±0
.74
.8±
0.8
4.7
±0
.74
.57
±0
.78
NS
0.0
07
NS
LD
Lch
ole
ster
ol,
mm
ol/
l2
.2±
0.5
2.2
7±
0.5
72
.2±
0.4
2.5
±0
.62
.1±
0.5
2.3
6±
0.5
2N
S0
.010
NS
HD
Lch
ole
ster
ol,
mm
ol/
l1
.69
±0
.32
1.5
3±
0.4
01
.63
±0
.30
1.5
1±
0.2
91
.73
±0
.31
1.4
2±
0.3
1N
SN
S0
.003
Tri
acylg
lyce
rols
,m
mol/
l1.1
7±
0.3
70
.85
±0
.29
1.1
6±
0.6
00
.96
±0
.50
1.2
3±
0.3
91
.08
±0
.45
NS
NS
0.0
04
Ox
idiz
edL
DL
,m
mo
l/l
26
.4±
5.0
23
.0±
5.5
26
.1±
7.0
25
.5±
7.7
25
.5±
6.2
24
.8±
6.5
NS
NS
NS
Ox
idiz
edL
DL
/LD
Lch
ole
ster
ol
12
.3±
2.5
10
.5±
2.7
12
.2±
3.0
10
.6±
4.1
12
.0±
2.3
10
.7±
2.3
NS
NS
NS
Ox
idiz
edL
DL
/HD
Lch
ole
ster
ol
16
.3±
4.6
16
.1±
5.6
16
.7±
6.0
17
.7±
7.3
15
.4±
5.4
18
.4±
6.1
NS
NS
0.0
07
pv
alu
esfo
rd
iffe
ren
ces
bet
wee
nth
eg
rou
ps
atb
asel
ine
are
anal
yze
db
yo
ne-
way
AN
OV
Aan
dd
iffe
ren
ces
of
chan
ges
inw
eig
ht,
BM
Io
rli
pid
sb
yli
nea
rre
gre
ssio
nm
odel
adju
sted
by
bas
elin
ele
vel
(n=
14
1)
Fig. 4 Changes in a total cholesterol and b LDL cholesterol
according to tertiles of weight change from baseline (pre-pregnancy
or 8–12 weeks’ gestation) to follow-up (1 year postpartum). Means
(95 % CI). p values for differences of changes in lipids are analyzed
by linear regression model adjusted by baseline level, age, body mass
index, parity and smoking
Lipids (2013) 48:1227–1235 1231
123
Discussion
Present study demonstrated that marked postpartum weight
retention (3.4 kg or more) was associated with elevated
concentration of TAG, ox-LDL/HDL-C ratio, and
decreased concentration of HDL-C. These results indicate
that postpartum weight retention might also cause athero-
genic lipid profile. Further, the correlations between weight
change and changes in blood lipids support these findings.
Elevated ox-LDL/HDL-C ratio is a predictor for coro-
nary artery disease [29]. In a Finnish population study,
elevated ox-LDL/HDL-C ratio was also connected with a
higher overall mortality among elderly [12]. The major
cardioprotective mechanism of HDL is the removal of
cholesterol from cells, but HDL also inhibits LDL
oxidation [8, 9]. Thus, decreased concentration or impaired
function of HDL-C is connected with increased concen-
tration of ox-LDL [1, 30]. Therefore, the ox-LDL/HDL-C
ratio considering both atherogenic ox-LDL and cardio-
protective HDL-C, stands out as a valuable biomarker for
evaluating the risk of cardiovascular diseases.
To our knowledge, this study is the first one to inves-
tigate the effects of postpartum weight retention on ox-
LDL. Compared to the few previous studies of men and
women without pregnancies, the association between
weight change and change in TAG, HDL-C and ox-LDL
was similar: favourable change in weight was accompanied
with favourable change in serum lipids and ox-LDL [16,
17]. Nevertheless, the current study did not show correla-
tion between postpartum weight retention and T-C or LDL-
Fig. 5 Changes in a HDL cholesterol and b triacylglycerols accord-
ing to tertiles of weight change from baseline (pre-pregnancy or
8–12 weeks’ gestation) to follow-up (1 year postpartum). Means
(95 % CI). p values for differences of changes in lipids are analyzed
by linear regression model adjusted by baseline level, age, body mass
index, parity and smoking
Fig. 6 Changes in a oxidized LDL lipids and b oxidized LDL/LDL
cholesterol ratio according to tertiles of weight change from baseline
(pre-pregnancy or 8–12 weeks’ gestation) to follow-up (1 year
postpartum). Means (95 % CI). p values for differences of changes
in lipids are analyzed by linear regression model adjusted by baseline
level, age, body mass index, parity and smoking
1232 Lipids (2013) 48:1227–1235
123
C, unlike several previous studies about weight change in
men and women without pregnancies [18, 19].
Lipid metabolism changes during pregnancy and may
both accentuate and defuse the effects of weight retention
on the changes in plasma lipids when comparing the levels
of the early pregnancy to the levels of 1 year postpartum.
During pregnancy, total, LDL- and HDL-cholesterol
(HDL-C) and TAG elevate [31], and ox-LDL also elevates,
especially in complicated pregnancies [32–34]. This would
explain why in the present study the concentration of ox-
LDL lipids decreased slightly even in the weight gain
group, although in the weight loss group a fivefold decrease
was seen compared to the weight gain group.
Women participating in the present study were all
evaluated to have had more or less risk factors for devel-
oping GDM at early pregnancy. When compared to women
at the same age in Finland or in other industrial countries,
these women, for example, had higher BMI [35], they were
more often obese, and they more often had a history of
GDM at the follow-up point [36]. Our previous study
showed that as many as almost one-fifth (18 %) of these
had metabolic syndrome according to the International
Diabetes Federation (IDF) criteria [37]. Metabolic syn-
drome is associated with increased levels of ox-LDL [15,
38]. It also might be the case that postpartum changes in
weight affect plasma lipids differently in this group than in
healthier women at the same age. Still, the study shows a
clear benefit of weight loss and disadvantage of weight
gain after pregnancy in terms of plasma lipids.
One limitation of this study is that at the follow-up,
the subjects were not specially queried about hormonal
contraception and medication for dyslipidemia, which
both have effects on lipid metabolism. However, when
medication for dyslipidemia was queried at the baseline,
none of the women reported such medication. Thus, it is
very improbable that lipid-lowering therapy was used in
postpartum stage 1-year after pregnancy. Further, statins
as a lipid lowering medication decrease the concentration
of serum lipids (particularly T-C and LDL-C), but the
effect of statins on the concentration of ox-LDL lipids is
contradictory and seems to depend on statins and
methods used to measure ox-LDL lipids [39–42]. The
effects of hormonal contraception on ox-LDL are not
properly known. However, it is known that hormonal
replacement therapy may somewhat influence on con-
centrations of ox-LDL [43]. In the present study, the
differences of the lipid results between the weight groups
are obviously not caused by the possible use of hormonal
contraception. On the contrary, the possible use of hor-
monal contraception within the weight groups would
rather make the study design more conservative and
diminished the differences.
We used self-reported weight before pregnancy, which
is not as reliable a measurement as using a scale. When
self-reported weight was compared to the available weight
measurement at the first maternity clinic visit, the mean
difference was\1 kg, which could easily be explained by a
minimal early-pregnancy weight gain. Thus the self-
reported weight is concluded to be quite accurate.
There is a need for further study about effect of post-
partum weight retention on cardiovascular events or on
other atherosclerosis risk markers than LDL oxidation. That
information would be valuable in investigating the rele-
vance of weight retention on cardiovascular health after
delivery. To our knowledge it has not been studied yet.
To conclude, postpartum weight retention is associated
with higher TAG and ox-LDL/HDL-C ratio as compared to
those who lost weight. Postpartum weight retention of
3.4 kg or more is associated with atherogenic lipid profile.
The present study shows that postpartum weight manage-
ment or weight reduction is important in management of
anti-atherogenic lipid profile.
Acknowledgments This study was funded by Competitive
Research Funding of the Tampere University Hospital, Juho Vainio
Foundation, Academy of Finland, Ministry of Education and Culture,
and Ministry of Social Affairs and Health. We are thankful to Tiina
Solakivi, PhD, associate professor at the Medical School at the
University of Tampere, who was responsible for the laboratory
testing.
References
1. Toikka JO, Ahotupa M, Viikari JSA, Niinikoski H, Taskinen MR,
Irjala K, Hartiala JJ, Raitakari OT (1999) Constantly low HDL-
Fig. 7 Changes in oxidized LDL/HDL cholesterol ratio according to
tertiles of weight change from baseline (pre-pregnancy or
8–12 weeks’ gestation) to follow-up (1 year postpartum). Means
(95 % CI). p values for differences of changes in lipids are analyzed
by linear regression model adjusted by baseline level, age, body mass
index, parity and smoking
Lipids (2013) 48:1227–1235 1233
123
cholesterol concentration relates to endothelial dysfunction and
increased in vivo LDL-oxidation in healthy young men. Ath-
erosclerosis 147:133–138
2. Tsimikas S, Miller YI (2011) Oxidative modification of lipo-
proteins: mechanisms, role in inflammation and potential clinical
applications in cardiovascular disease. Curr Pharm Des 17:27–37
3. Chisolm GM 3rd, Hazen SL, Fox PL, Cathcart MK (1999) The
oxidation of lipoproteins by monocytes-macrophages. Biochemical
and biological mechanisms. J Biol Chem 274(37):25959–25962
4. Ahotupa M, Vasankari TJ (1999) Baseline diene conjugation in
LDL lipids: an indicator of circulating oxidized LDL. Free Radic
Biol Med 27:1141–1150
5. Wang JS, Chen YW, Chow SE, Ou HC, Sheu HH (2005) Exer-
cise paradoxically modulates oxidized low density lipoprotein-
induced adhesion molecules expression and trans-endothelial
migration of monocyte in men. Thromb Heamost 94:846–852
6. Meisinger C, Baumert J, Khuseyinova N, Loewel H, Koenig W
(2005) Plasma oxidized low-density lipoprotein, a strong pre-
dictor for acute coronary heart disease events in apparently
healthy, middle-aged men from the general population. Circula-
tion 112(5):651–657
7. Juul K, Nielsen LB, Munkholm K, Stender S, Nordestgaard BG
(1996) Oxidation of plasma low-density lipoprotein accelerates
its accumulation and degradation in the arterial wall in vivo.
Circulation 94:1698–1704
8. Kontush A, Chapman MJ (2010) Antiatherogenic function of
HDL particle subpopulations: focus on antioxidative activities.
Curr Opin Lipidol 21(4):312–318
9. Rye KA, Bursill CA, Lambert G, Tabet F, Barter PJ (2009) The
metabolism and anti-atherogenic properties of HDL. J Lipid Res
50(Suppl):S195–S200
10. Bandeali S, Farmer J (2012) High-density lipoprotein and ath-
erosclerosis: the role of antioxidant activity. Curr Atheroscler
Rep 14(2):101–107
11. Johnston N, Jernberg T, Lagerqvist B, Siegbahn A, Wallentin L
(2006) Improved identification of patients with coronary artery
disease by the use of new lipid and lipoprotein biomarkers. Am J
Cardiol 97(5):640–645
12. Linna M, Ahotupa M, Lopponen MK, Irjala K, Vasankari T
(2013) Circulating oxidised LDL lipids, when proportioned to
HDL-c, emerged as a risk factor of all-cause mortality in a
population-based survival study. Age Ageing 42(1):110–113
13. Haslam DW, James WP (2005) Obesity. Lancet 366(9492):
1197–1209 Review
14. Njajou OT, Kanaya AM, Holvoet P, Connelly S, Strotmeyer ES,
Harris TB, Cummings SR, Hsueh WC, Health ABC Study (2009)
Association between oxidized LDL, obesity and type 2 diabetes
in a population-based cohort, the Health, Aging and Body
Composition Study. Diabetes Metab Res Rev 25(8):733–739
15. Holvoet P, Lee DH, Steffes M, Gross M, Jacobs DR Jr (2008)
Association between circulating oxidized low-density lipoprotein
and incidence of the metabolic syndrome. JAMA 299(19):
2287–2293
16. Vasankari T, Fogelholm M, Kukkonen-Harjula K, Nenonen A,
Kujala U, Oja P, Vuori I, Pasanen P, Neuvonen K, Ahotupa M
(2001) Reduced oxidized low-density lipoprotein after weight
reduction in obese premenopausal women. Int J Obes Relat
Metab Disord 25(2):205–211
17. Linna MS, Borg P, Kukkonen-Harjula K, Fogelholm M, Nenonen
A, Ahotupa M, Vasankari TJ (2007) Successful weight mainte-
nance preserves lower levels of oxidized LDL achieved by weight
reduction in obese men. Int J Obes (Lond) 31(2):245–253
18. Poobalan A, Aucott L, Smith WC, Avenell A, Jung R, Broom J,
Grant AM (2004) Effects of weight loss in overweight/obese
individuals and long-term lipid outcomes—a systematic review.
Obes Rev 5(1):43–50
19. Reinehr T, Andler W (2004) Changes in the atherogenic risk
factor profile according to degree of weight loss. Arch Dis Child
89(5):419–422
20. Wolfe WS, Sobal J, Olson CM, Frongillo EA Jr (1997) Parity-
associated body weight: modification by sociodemographic and
behavioural factors. Obes Res 5:131–141
21. Gore SA, Brown DM, West DS (2003) The role of postpartum
weight retention in obesity among women: a review of the evi-
dence. Ann Behav Med 26(2):149–159 Review
22. Brown WJ, Hockey R, Dobson AJ (2010) Effects of having a
baby on weight gain. Am J Prev Med 38:163–170
23. Luoto R, Mannisto S, Raitanen J (2011) Ten-year trends in
obesity by parity-results from a national FINRISK population
study. Gend Med 8(6):399–406
24. Luoto R, Kinnunen TI, Aittasalo M, Kolu P, Raitanen J, Ojala K,
Mansikkamaki K, Lamberg S, Vasankari T, Komulainen T,
Tulokas S (2011) Primary prevention of gestational diabetes
mellitus and large-for-gestational-age newborns by lifestyle
counseling: a cluster-randomized controlled trial. PLoS Med.
doi:10.1371/journal.pmed.1001036
25. Luoto RM, Kinnunen TI, Aittasalo M, Ojala K, Mansikkamaki K,
Toropainen E, Kolu P, Vasankari T (2010) Prevention of gesta-
tional diabetes: design of a cluster-randomized controlled trial
and one-year follow-up. BMC Pregnancy Childbirth. doi:10.
1186/1471-2393-10-39
26. American Diabetes Association (2006) Diagnosis and classifica-
tion of diabetes mellitus. Diabetes Care 29(Suppl 1):S43–S48
27. Ahotupa M, Ruutu M, Mantyla E (1996) Simple methods of
quantifying oxidation products and antioxidant potential of low
density lipoproteins. Clin Biochem 29:139–144
28. Ahotupa M, Marniemi J, Lehtimaki T, Talvinen K, Raitakari OT,
Vasankari T, Viikari J, Luoma J, Yla-Herttuala S (1998) Baseline
diene conjugation in LDL lipids as a direct measure of in vivo
LDL oxidation. Clin Biochem 31:257–261
29. Huang H, Mai W, Liu D, Hao Y, Tao J, Dong Y (2008) The
oxidation ratio of LDL: a predictor for coronary artery disease.
Dis Markers 24(6):341–349
30. Navab M, Reddy ST, Van Lenten BJ, Anantharamaiah GM,
Fogelman AM (2009) The role of dysfunctional HDL in athero-
sclerosis. J Lipid Res 50(Suppl):S145–S149
31. Bartels A, Egan N, Broadhurst DI, Khashan AS, Joyce C, Sta-
pleton M, O’Mullane J, O’Donoghue K (2012) Maternal serum
cholesterol levels are elevated from the 1st trimester of preg-
nancy: a cross-sectional study. J Obstet Gynaecol 32(8):747–752
32. Fialova L, Mikulıkova L, Malbohan I, Benesova O, Stıpek S, Zima
T, Zwinger A (2002) Antibodies against oxidized low density
lipoproteins in pregnant women. Physiol Res 51(4):355–361
33. Toescu V, Nuttall SL, Martin U, Nightingale P, Kendall MJ,
Brydon P, Dunne F (2004) Changes in plasma lipids and markers
of oxidative stress in normal pregnancy and pregnancies com-
plicated by diabetes. Clin Sci (Lond) 106(1):93–98
34. Makedou K, Kourtis A, Gkiomisi A, Toulis KA, Mouzaki M,
Anastasilakis AD, Gerou S, Gavana E, Agorastos T (2011)
Oxidized low-density lipoprotein and adiponectin levels in
pregnancy. Gynecol Endocrinol 27(12):1070–11073
35. Peltonen M, Harald K, Mannisto S, Saarikoski L, Peltomaki P,
Lund L, Sundvall J, Juolevi A, Laatikainen T, Alden-Nieminen
H, Luoto R, Jousilahti P, Salomaa V, Taimi M, Vartiainen E
(2008) The National FINRISK 2007 Study. Statistics, Publica-
tions of the National Public Health Institute B35/2008 (in Finn-
ish), Helsinki, Finland
36. Schneider S, Bock C, Wetzel M, Maul H, Loerbroks A (2012)
The prevalence of gestational diabetes in advanced economies.
J Perinat Med 40(5):511–520
37. Puhkala J, Kinnunen TI, Vasankari T, Kukkonen-Harjula K,
Raitanen J, Luoto R (2013) Prevalence of metabolic syndrome
1234 Lipids (2013) 48:1227–1235
123
one year after delivery in Finnish women at increased risk for
gestational diabetes mellitus during pregnancy. J Pregnancy.
doi:10.1155/2013/139049
38. Valle-Gottlieb MG, da Cruz IB, Duarte MM, Moresco RN,
Wiehe M, Schwanke CH, Bodanese LC (2010) Associations
among metabolic syndrome, ischemia, inflammatory, oxidatives,
and lipids biomarkers. J Clin Endocrinol Metab 95(2):586–591
39. Vasankari T, Ahotupa M, Viikari J, Nuotio I, Tikkanen M (2005)
Effects of statin therapy on LDL oxidation. Atherosclerosis
179:207–209
40. Kostapanos MS, Milionis HJ, Elisaf MS (2008) An overview of
the extra-lipid effects of rosuvastatin. J Cardiovasc Pharmacol
Ther 13(3):157–174
41. Resch U, Tatzber F, Budinsky A, Sinzinger H (2006) Reduction
of oxidative stress and modulation of autoantibodies against
modified low-density lipoprotein after rosuvastatin therapy. Br J
Clin Pharmacol 61(3):262–274
42. Dong Y, Steffen BT, Cao J, Tsai AK, Ordovas J, Straka R, Zhou X,
Kabagambe E, Hanson NQ, Arnett D, Tsai MY (2011) Effects of
fenofibrate on plasma oxidized LDL and 8-isoprostane in a sub-
cohort of GOLDN participants. Atherosclerosis 214(2):422–425
43. Ahotupa M, Rauramo I, Vasankari T, Skouby SO, Hakonen T
(2004) Estrogen replacement therapy in combination with con-
tinuous intrauterine progestin administration reduces the amount
of circulating oxidized LDL in premenopausal women: depen-
dence on the dose of progestin. Ann Med 36(4):278–284
Lipids (2013) 48:1227–1235 1235
123