HIGH
SERUM RATIO OF SOLUBLE FMS-LIKE TYROSINE KINASE 1 (sFlt-1) TO PLACENTAL GROWTH
FACTOR (PIGF) AND HIGH LEVEL OF LOW-DENSITY LIPOPROTEIN (LDL) AS RISK FACTORS
OF PREECLAMPSIA
Kevin Agastya Duarsa, A.A.N. Jaya Kusuma, Endang
Sri Widiyanti, I Wayan Megadhana,
Putu Doster Mahayasa, Ryan Saktika
Mulyana
Departement of Obstetrics
and Gynecology, Faculty of Medicine, Udayana
University/Prof. IGNG Ngoerah Hospital,
Bali, Indonesia
Email: [email protected], [email protected], [email protected],
[email protected], [email protected],
rya[email protected]ahoo.com
Keywords: Low
Density Lipoprotein, Placental Growth Factor, Preeclampsia, Soluble FMS-Like
Tyrosine Kinase 1. |
ABSTRACT Preeclampsia is an obstetric disease that is a health problem
worldwide, including in Indonesia. Several studies have shown that changes in
the maternal spiral arteries are thought to lead to preeclampsia.
Preeclampsia in this decade has been associated with changes in angiogenesis
regulatory proteins originating from the placenta and circulating in the
mother's blood circulation, namely soluble FMS-like tyrosine kinase 1
(sFlt-1) and placental growth factor (PlGF). The
author was interested in examining the ratio of sFlt-1/PIGF and low-density
lipoprotein (LDL) to the incidence of preeclampsia in pregnant women. This
study used a case control analytic observational design. The research sample
was selected by consecutive sampling of 20 cases and 20 controls. Univariate
analysis was used to describe patient characteristics descriptively, and bivariate
analysis was used to determine the relationship between the 2 variables There
is no significant difference in the characteristics of the research subjects.
Low PIGF levels are a risk factor for preeclampsia (OR 4.33; p 0.0302) with a
cut-off value of 24.5. High sFlt-1 levels are a risk factor for preeclampsia
(OR 4.33; p 0.027) with a cut-off value of 869.5. A high sFlt-1/PIGF ratio is
a risk factor for preeclampsia (OR 4.33 p 0.030) with a cut-off value of 38.
High LDL levels are a risk factor for preeclampsia (OR 6.0; p 0.013) with a
cut-off value of 150 ,2. Low placental growth factor (PIGF), high levels of
soluble FMS-like tyrosine kinase 1 (sFlt-1), and high levels of LDL are risk
factors of preeclampsia in pregnant women. |
Article Info |
Article entered
04-05-23, Revised 15-05-23, Accepted 20-05-23 |
INTRODUCTION
Preeclampsia is an obstetric disease that has become a health problem
throughout the world, including in Indonesia. Preeclampsia is associated with
high maternal and infant mortality rates, so early detection of preeclampsia is
very important. Various studies to understand early detection in pregnant women
suspected of being at risk of preeclampsia before signs and symptoms appear
have been carried out, to angiogenic and antiangiogenic protein analysis which
is expected to provide innovative input as predictors in more specific early
detection of preeclampsia. Biomarkers involved in various complexities of
placental abnormalities and endothelial dysfunction have been studied, one of
which is still little discussed and studied in Indonesia is the levels of sFlt-1,
PIGF, and LDL involved in endothelial dysfunction as the most important etiology in the pathogenesis of preeclampsia.
In 2017, as many as 295,000 women worldwide died during pregnancy and
childbirth (Organization, 2011). Hemorrhage, hypertensive diseases, and
sepsis contributed to half of maternal mortality worldwide from 2003 to 2009 (Say et al., 2014). Nearly one-tenth of maternal mortality in Asia and Africa, and
one-quarter of maternal mortality in Latin America are linked to hypertension
during pregnancy. Among these diseases, preeclampsia and eclampsia have the
greatest impact on maternal and newborn morbidity and
mortality (Organization, 2011).
Proteinuria and elevated blood pressure are diagnostic criteria that
have been used, but both criteria are nonspecific. Measurements of proteinuria
are of poor accuracy and complications due to proteinuria often arise before
proteinuria is significant. Current clinical guidelines suggest that the
diagnosis of preeclampsia be made based on the presence of hypertension and
signs of multiple organ failure. The clinical manifestations and course of
preeclampsia vary widely, suggesting that current diagnostic guidelines are
insufficient to cover the entire syndrome (Zeisler et al., 2016).
Until now, the cause of preeclampsia is still not thoroughly understood,
but some research suggests that changes in the maternal spiral arteries are thought
to lead to preeclampsia (Zeisler et al., 2016). Preeclampsia in this decade is associated with changes in angiogenesis
regulatory proteins that originate in the placenta and circulate in the
mother's blood circulation, namely soluble FMS-like Tyrosine Kinase 1 (sFlt-1)
and Placental Growth Factor (PlGF) (Moufarrej, 2021). In the cases of preeclampsia that have been studied, it was found that
there was an increase in sFlt-1 levels and a decrease in PlGF
levels in blood serum. sFlt-1 is an antagonist of PIGF and Vascular Endothelial
Growth Factor (VEGF), which causes vasoconstriction and endothelial damage
leading to fetal growth inhibition and preeclampsia.
Therefore, a high ratio of sFlt-1 to PIGF is associated with an increased risk
of preeclampsia (Zeisler et al., 2016).
Maynard (2003) research shows that sFlt-1 plays a role in the
pathogenesis of preeclampsia, other studies show the usefulness of this
angiogenic marker in the diagnosis and prediction and management of
preeclampsia and other placental disorders. Other studies have shown that this
imbalance of angiogenic and antiangiogenic factors may also describe the
prognosis of preeclampsia. An increase in the sFlt-1/PIGF ratio can be detected
as early as the second half of pregnancy in pregnant women suffering from
preeclampsia and other placental disorders. This angiogenic factor balance
disorder is also known to be detected before the appearance of clinical manifestations
of the disease, so it can be used for screening pregnant women who are at risk
of complications in their pregnancy, especially preeclampsiaa).
In preeclampsia, endothelial dysfunction occurs which can be caused by
changes in Low Density Lipoprotein (LDL). LDL is a lipoprotein that transports
the most cholesterol in the blood. High LDL levels cause deposition of
cholesterol in the arteries. In pregnancy there is a change in fat profile,
namely an increase in triglycerides followed by an increase in other fats. Hypertriglycerides cause changes in the spectrum of
Intermediate Density Lipoprotein (IDL) into LDL particles smaller in size, have
higher density and are atherogenic, It is suspected that there is a
relationship between preeclampsia and increased LDL levels which causes
endothelial dysfunction and causes imbalance in the production of vasodilator
substances such as prostacyclin and nitrate oxidants with vasoconstrictors such
as thromboxane and endothelium I so that vasoconstriction will occur� broad.
Based on the above exposure, it can be seen that both sFlt-1, PGIF and
LDL have an important role in the pathogenesis of preeclampsia. These factors,
if expressed in the form of sFlt-1 / PGIF ratio, and LDL have the potential to
be used as predictors in the study of pregnant women at risk of preeclampsia
because they can be detected before the appearance of clinical manifestations.
This is expected to reduce the number of morbidity and death rates arising from
late management. Therefore, the authors are interested in examining the ratio
of sFlt-1 / PIGF and LDL to the incidence of preeclampsia in pregnant women.
The purpose of this study, to prove low levels of Placental Growth Factor (PIGF) is a risk factor for preeclampsia, proves that high levels of soluble FMS-like Tyrosine Kinase 1 (sFlt-1) are risk factors for preeclampsia. Proving a high ratio of soluble FMS-like Tyrosine Kinase 1 (sFlt-1) to Placental Growth Factor (PIGF) is a risk factor for preeclampsia and proving high levels of Lowdensity Lipoprotein (LDL) is a risk factor for preeclampsia.
The theoretical benefits of this study are expected to contribute knowledge about the ratio of soluble FMS-like Tyrosine Kinase 1 (sFlt-1) levels to Placental Growth Factor (PIGF) levels and high Lowdensity Lipoprotein (LDL) levels to the incidence of preeclampsia.
This study uses a case control
analytic observational design. This study was conducted to assess the ratio of
sFlt-1/PIGF and LDL levels as a risk factor for preeclampsia. The sample of
this study were pregnant women who came to the Obstetrics and Gynecology
Polyclinic at Prof. Hospital. dr. I.G.N.G Ngoerah Denpasar and the Delivery
Room of the Obstetrics and Gynecology IGD Prof. Hospital. dr. I.G.N.G Ngoerah
Denpasar with a gestational age of 20-40 weeks and suffering from preeclampsia.
While the controls in this study were pregnant women with a gestational age of
20-40 weeks without preeclampsia. For both the case and control groups, 3 cc of
venous blood was collected for examination of serum PIGF and SFLT-1 levels and
3 cc for examination of LDH. This research was conducted at the Obstetrics and
Gynecology Polyclinic, RSUP Prof. dr. I.G.N.G Ngoerah Denpasar and the Delivery
Room of the Obstetrics and Gynecology IGD Prof. Hospital. dr. I.G.N.G Ngoerah
Denpasar. This research was conducted from December 2021 to December 2022.
RESULTS AND DISCUSSION
Characteristics of the Research Sample
A total of 40 research samples were collected in this
study, each consisting of 20 pregnant women without preeclampsia and diagnosed
with preeclampsia. The results of the data normality test using the Shapiro
Wilk test showed that the data on maternal age, maternal age, sFlt-1 levels,
PIGF levels, and the sFlt-1/PIGF ratio were not normally distributed
(p<0.05) while body mass index (BMI) data and LDL levels were normally distributed
(p>0.05). There were no differences in basic characteristics such as
maternal age, gestational age and BMI before pregnancy between patients with
and without preeclampsia. Patients with preeclampsia tend to have an older
maternal age, a higher pre-pregnancy BMI and a lower gestational age (Table
1</0,05)>).
Table 1.
Characteristics of Research Samples
Characteristic |
Total (N=40) |
Preeclampsia
Status |
P value |
||
Yes (N=20) |
No (N=20) |
|
|
||
Age (years), mean (�SD) |
30,25 (�3,74) |
30,9 (�4,39) |
29,6 (�2,92) |
0,192 |
|
Parity, mean (�SD) |
1,875 (�0,79) |
1,85 (�0,745) |
1,90 (�0,852) |
0,798 |
|
Gestational Age (weeks), mean (�SD) |
31,5 (�3,37) |
30,5 (�3,14) |
32,45 (�3,39) |
0,091 |
|
BMI (kg/m2), mean (�SD) |
23,2 (�2,91) |
23,58 (�2,8) |
22,86 (�3,0) |
0,438 |
|
Low levels of PIGF as a risk factor for preeclampsia
The mean PIGF level in all samples was 26.47 (�9.0).
Patients with preeclampsia tended to have lower PIGF levels compared to
patients without preeclampsia (24.3 vs. 28.6). The Mann-Whitney test shows this
difference is statistically significant (p = 0.02) (Table 2).
Table 2
PIGF Levels Based on Preeclampsia Status
Characteristic |
Total (N=40) |
Preeclampsia
status |
P value |
|
Ya (N=20) |
No (N=20) |
|||
PIGF, mean (�SD) |
26,47� (�9,0) |
24,3 (�10,5) |
28,6 (�6,7) |
0,02 |
A receiver operating characteristics (ROC) curve was
created to determine the cutoff point of PIGF levels based on preeclampsia
status (Figure 5.2). The cutoff point value of PIGF levels to predict the
incidence of preeclampsia was 24.5 with a sensitivity value of 65% and
specificity of 65%. The under curve area (AUC) value is 0.714 (p=0.021;
Confidence interval [IK] 95% 0.552 � 0.875).
Figure
1. ROC Curve of PIGF Levels by Preeclampsia Status
Patients were then classified into high (>24.5) and
low (≤24.5) PIGF levels. Preeclampsia patients had a higher proportion of
low PIGF levels than non-preeclampsia patients (65% vs. 35%). High PIGF levels
tend to be a protective factor for preeclampsia, with patients with low PIGF
levels having a 4.33 times higher risk of preeclampsia than high PIGF levels.
These results proved to be statistically significant (p = 0.0302).
Table 3
Association Of PIGF Levels With Preeclampsia Status
PIGF levels |
Preeclampsia
Status |
OR value (IK 95%) |
P value |
|
Ya (N=20) |
No (N=20) |
|
|
|
Low |
13 (65%) |
6 (30%) |
4,333 (1,150 � 16,323) |
0,0302 |
Tall |
7 (35%) |
14 (70%) |
Kadar sFlt-1 yang Tinggi Sebagai Faktor Risiko
Preeklampsia
The mean sFlt-1 levels in all samples were 873.5
(�439.6). Patients with preeclampsia tended to have higher levels of sFlt-1
compared to patients without preeclampsia (1038.9 vs. 709). The Mann-Whitney
test shows this difference is statistically significant (p = 0.026) (Table 4).
Table 4.
sFlt-1 Levels Based on Preeclampsia Status
Characteristic |
Total (N=40) |
Preeclampsia
status |
P value |
|
Ya (N=20) |
No (N=20) |
|||
sFlt-1, mean (�SD) |
873,5 (�439,6) |
1038,9 (�518,4) |
708 (�265,1) |
0,026 |
A receiver
operating characteristics (ROC) curve was created to determine the cutoff point
of sFlt-1 levels based on preeclampsia status (Figure 5.2). The cutoff point
value of sFlt-1 levels to predict the incidence of preeclampsia was 869.5 with
a sensitivity value of 65% and specificity of 70%. The area under curve (AUC)
value is 0.704 (p=0.027; Confidence interval [IK] 95% 0.541 � 0.866).
Figure 2 ROC Curve of sFlt-1 Levels
based on Preeclampsia Status
Patients were then classified into high (>869.5)
and low (≤869.5) sFlt-1 levels. As many as 65% of preeclampsia patients
and only 30% of patients without preeclampsia have high sFlt-1 levels. Patients
with high sFlt-1 levels had a 4.33 times higher chance of developing
preeclampsia compared with low sFlt-1 levels (p = 0.027). These results are
summarized in Table 5.
Table 5.
Relationship of Sflt-1 Levels Category with Preeclampsia Status
sFlt-1 levels |
Preeclampsia
Status |
Value OR (IK 95%) |
P value |
|
Ya (N=20) |
No (N=20) |
|||
Tall |
13 (65%) |
6 (30%) |
4,33 (1,15 � 16,32) |
0,027 |
Low |
7 (35%) |
14 (70%) |
High Sflt-1/PIGF Ratio as a Risk Factor For
Preeclampsia
The mean sFlt-1/PIGF ratio in all samples was 36.37
(�22.8). Patients with preeclampsia tended to have a higher sFlt-1/PIGF ratio
compared to patients without preeclampsia (46.56 vs. 26.18). The Mann-Whitney
test shows this difference is statistically significant (p = 0.002) (Table 6).
Table 6.
sFlt-1/PIGF Ratio Based On Preeclampsia Status
Characteristic |
Total (N=40) |
Preeclampsia
Status |
P value |
|
Ya (N=20) |
No (N=20) |
|||
Ratio sFlt-1/PIGF, mean (�SD) |
36,37 (�22,8) |
46,56 (�26,62) |
26,18 (�12,12) |
0,002 |
The sFlt-1/PIGF ratio was also classified into low
(<38) and high (>38). There was a significant difference between the
sFlt-1/PIGF ratio in the non-PE and PE groups (p=0.030).
Table 7.
Relationship of sFlt-1/PIGF Ratio To Preeclampsia Status
Ratio sFlt-1/PIGF |
Preeclampsia
Status |
Value OR (IK 95%) |
P value |
||
Ya (N=20) |
No (N=20) |
4.33 (1,15 � 16,32) |
0.030 |
||
Tall |
12 (70%) |
6 (30%) |
|||
Low |
8 (40%) |
14 (70%) |
|
|
|
High LDL Levels as a Risk Factor for Preeclampsia
The mean LDL level in all samples was 139.8 (�29.0).
Patients with preeclampsia tended to have higher LDL levels compared to
patients without preeclampsia (150.2 vs. 129.4). The Mann-Whitney test shows
this difference is statistically significant (p = 0.021) (Table 8).
Table 8.
LDL Levels Based on Preeclampsia Status
Characteristic |
Total (N=40) |
Preeclampsia
Status |
P value |
|
Ya (N=20) |
No (N=20) |
|||
LDL levels |
139,8 (�29,0) |
150,2 (�31,9) |
129,4 (�22,0) |
0,021 |
LDL levels are divided into
low and high. There was a significant difference in LDL levels between the two
groups (p = 0.013).
Table 9.
Relationship of LDL levels to preeclampsia status
LDL levels |
Preeclampsia
Status |
Nilai OR (IK 95%) |
Nilai p |
||
Ya (N=20) |
No (N=20) |
6.0 (1.4583 � 24.6868) |
0.013 |
||
Tall |
16 (80%) |
8 (40%) |
|||
Low |
4 (20%) |
12 (60%) |
|
|
|
Low levels of placental growth factor (PIGF) as a risk
factor for preeclampsia
Placental growth factor (PIGF) is a member of the
vascular endothelial growth factor (VEGF) family that is mostly expressed in
the placenta and a small part expressed in other tissues such as the heart,
lungs, thyroid, liver, skeletal muscle and bones. This protein is secreted as
homodimers PlGF-1 to PlGF-4 (Torry et
al., 1998). The
isoforms PlGF-1 and PlGF-2 are the most abundant forms of PIGF including
pregnancy (Chau et al., 2017).
In a normal pregnancy, PlGF concentrations are
initially low in the first trimester of pregnancy and increase from weeks 11 to
12 onwards until peaking at week 30. Normal PlGF concentrations depend on
gestational age, with the lower limit of normal peaking at around 141 pg/ml at
30 weeks gestation and then dropping to 23 pg/ml at term (Saffer et al., 2013). In this study,
the median PIGF level was 28.5 pg / ml. This result is much lower than the
maximum level obtained from the results of the previous study. This difference
in results may be explained because after 29-30 weeks gestation, PIGF levels in
normal pregnancy have begun to decline (Chau et al., 2017). In this study,
the median age in this study was 33 weeks, specifically in the normotensive
group. However, the concentration of PIGF is much lower than the results of
other studies that get higher concentrations of 175.5 pg / ml in the second
trimester and 753 pg / ml in the third trimester (Tidwell et al., 2001).
Serum and urine PLGF were found to decrease in women
both at the time of diagnosis and before the onset of preeclampsia syndrome.
The decrease in PlGF occurs both in its expression and also in free PlGF levels (Levine
et al., 2004). Another
study found that PIGF concentrations of less than 62.5 pg/ml increased the risk
of preeclampsia. When compared with these concentration limits, we found that
the median PIGF level was much lower at 22.5 pg/ml in the preeclampsia group.
The risk of preeclampsia increased with a decrease in PIGF concentration,
namely 49.6% at levels of 12-99 pg / l and 83.6% at PIGF levels less than 12 pg
/ l, while the risk of preeclampsia was only 16.1% at PIGF levels ≥ 100
pg / ml (Duhig et al., 2019).
The study comparing PIGF levels between normal
pregnancy and preeclampsia found patients with PIGF levels less than 62.5 pg/ml
had a 3.2 times higher risk than those below that limit. Likewise, the results
of this study found that PIGF levels were significantly higher in normal
pregnancy than preeclampsia (p = 0.02).
Low PLFGF in pregnancy may be a consequence of
abnormal inplantations in the placentation and a contributing factor to
abnormal placental growth that continues during the second half of pregnancy (Novelia et al., 2019). The hypothesis
that PlGF is an indicator of abnormal placentation is supported by also low
PIGF levels in women without preeclampsia who give birth to babies with low
birth weight (Poon et al., 2008). Other data
also postulate that the decrease in PIGF levels in preeclampsia occurs due to
persistent placental hypoxia (Chau et al., 2017). But other data
got different results, where PIGF expression increased (Regnault et al., 2002) or no change (Hoeller et al., 2017).
In this study, the mean PIGF levels in all samples were
26.47 (�9.0). Patients with preeclampsia tended to have lower PIGF levels
compared to patients without preeclampsia (24.3 vs. 28.6). The Mann-Whitney
test shows this difference is statistically significant (p = 0.02).
High soluble FMS-like Tyrosine Kinase 1 (sFlt-1) as a
risk factor for preeclampsia
Soluble Fms-like tyrosine kinase-1 (sFlt-1) is the
soluble form of receptor vascular endothelial growth factor (VEGF) and
placental growth factor (PlGF). This vascular endothelial growth factor
secretes dimeric glycoproteins that participate in vasculogenesis and
anginogenesis (Lecarpentier & Tsatsaris, 2016).
Previous studies found that sFlt-1 levels in
non-preeclampsia pregnancies were 3,981.62 � 4,921.5 pg/ml. While in
preeclampsia, sFlt-1 levels were 11,231� 8,390.3 pg / ml. In the study, it was
also obtained with a cut off point of >4,505.50 pg / ml can predict
preeclampsia with a sensitivity of 79.3% and specificity of 82.8% and the risk
of preeclampsia increased 18 times at levels above the cut off point (Putra et al., 2016). Other results
of other studies obtained lower results, at 29-36 weeks gestation, sFlt-1
levels were 2,641.0 (range 1,811.3 to 12,661.0) in preeeclampsia and 1,439.0
(range 428.8 to 4,691.0) (Hanita et al., 2014). In this study,
the median sFlt-1 levels were 890 pg / ml in preeclampsia and 754.5 pg / ml in
non-preeclampsia.
In preeclampsia, the concentration of sFlt-1 increases
in the second trimester, usually 4-5 weeks before the onset of preeclampsia
syndrome. The concentration increased 2 to 4 times compared to
non-preeclampsia. At the same gestational age, sFlt-1 concentrations were
higher in peeclampsia compared to non-preeclampsia (Lecarpentier & Tsatsaris, 2016). In this study, sFlt-1 levels were
significantly higher in preeclampsia compared to non-preeclampsia (p = 0.026).
This result is comparable to the results of the previous Mega Putra et al,
(2016) research which also had significant differences between preeclampsi and
non-preeclampsia pregnancies (p < 0.005). In vivo studies have also
explained that high levels of sFlt-1 induce disruption of the spiral artery
remodeling process in preeclampsia (Vogtmann et al., 2021).
Preeclampsia is associated with an increase in
circulating sFlt-1 protein, as mentioned above. Increased production of sFlt-1
may come from the placenta, this is because the sFlt-1 mRNA of placental
preeclampsia levels drop within 48 hours after delivery.� In addition, the administration of exogenous
sFlt-1 in vivo research also causes clinical and pathological preeclampsia such
as hypertension and glomerular endotheliosis (Roberts & Rajakumar, 2009). In addition, sFlt-1 acts as an antagonist
of VEGF and PlGF. VEGF plays a role in stimulating angiogenesis and to maintain
endothelial integrity, especially in fenestrated endotheliums such as those in
glomerular capillaries. Administration of VEGF antagonists as a cancer
treatment is also associated with proteinuria and hypertension (Kabbinavar et al., 2003). VEGF also
recruits endothelial progenitor cells to the site of endothelial injury (Urbich et al., 2005). So that with
an increase in sFlt-1 this will interfere with the remodeling process of the
placenta as in preeclampsia.
In this study, the mean level of sFlt-1 in all samples
was 873.5 (�439.6). Patients with preeclampsia tended to have higher levels of
sFlt-1 compared to patients without preeclampsia (1038.9 vs. 709). The
Mann-Whitney test shows this difference is statistically significant (p =
0.026).
High ratio of soluble FMS-like Tyrosine Kinase 1
(sFlt-1) to Placental Growth Factor (PIGF) Levels as a Risk Factor For
Preeclampsia
Some
studies show increased levels of sFlt-1 and decreased levels of PIGF in women
with preeclampsia compared to non-preeclampsia pregnancies (Anderson et al., 2012). Thus the
sFlt-1:PlGF ratio is also useful in distinguishing preeclampsia patients from
non-preeclampsia (Chau et al., 2017).
In this study, the median ratio of sFlt-1: PlGF in
preeclampsia was 40.1 while in non-preeclampsia it was 23.7. The difference
between the two ratios is statistically significant (p = 0.002). These results
are also supported by other studies, but with more striking results. In the
study of Nikuei et al, (2020) obtained a ratio of 91.33 in preeclampsia
patients and 17.62 in non-preeclampsia (p<0.001).
In addition, this ratio also serves as a good
predictive factor against preeclampsia. The results of this study are supported
by the results of other studies that obtained an sFlt-1: PlGF ratio of more
than 38 has a 2.8 times higher risk of preeclampsia (Ohkuchi et al,
2021). Another study also found that a ratio of more than 38 had a positive
predictive value of 36.7% experiencing preeclampsia in 4 weeks, and sensitivity
of 66.2% and specificity of 83.1%.
In this study, the mean ratio of sFlt-1 / PIGF in all
samples was 36.37 (�22.8). Patients with preeclampsia tended to have a higher
sFlt-1/PIGF ratio compared to patients without preeclampsia (46.56 vs. 26.18).
The Mann-Whitney test shows this difference is statistically significant (p =
0.002).
High Levels of Low Density Lipoprotein (LDL) as a Risk
Factor For Preeclampsia
In this study, LDL levels in preeclampsia were 150.2
(�31.9) mg / dl while in non-preeclampsia pregnancies were 129.4 (�22.0) mg /
dl. The same results were also obtained in previous studies that found LDL
levels in preeclampsia 133.92 (�38.77) mg / dl higher than normotensive which
was 112.41 � 36.08 mg / dl (Tesfa et al., 2020). So is research
�(Kozan et
al., 2015) received 147�61 mg/dl in preeclampsia and
135�59 mg/dl in non-preeclampsia.�
Another study also found pregnant women who had LDL levels of >50 U/l
had a 2.9 times higher risk of developing preeclampsia compared to levels below
(Qiu et al., 2006).� Other studies have had similar results.
Several other studies have had different results.
Research by Rajyalakshmi and Rao, (2016) shows no significant increase in LDL
in preeclampsia and eclampsia. Likewise, the results of research Harmi et al
(2012) found no difference in LDL cholesterol levels between preeclampsia and
overweight pregnant women with non-preeclampsia blood pressure.
Although some data show an association between LDL levels
and preeclampsia, it is still unclear whether high cholesterol levels are a
predisposing factor that occurs before preeclampsia or vice versa increases
after preeclampsia. Theories that explain the relationship are the occurrence
of hemodynamic disorders, oxidative stress, exposure to inflammatory cytokines
and hypercholesterolemia. In the pathogenesis of preeclampsia, characteristic
lesions of the placenta are fibrin deposits, acute atheros, and thrombosis.
These lesions are almost the same shape as lesions found in atherosclerosis.
Based on these findings, there may be pathophysiological similarities between
preeclampsia and atherosclerosis. An abnormal fat profile is also a risk factor
for preeclampsia (Lowe et al., 2015). Several factors such as fatty acids,
lipoproteins, lipid peroxidases, TNF ά, fibronectin products and
microvilli fragments from sinsintiotrophoblast cells, all of these factors are
the result of intravascular inflammatory responses encountered in pregnancy and
have increased preeclampsia (Lowe et al., 2015).
In this study, the mean LDL levels in all samples were
139.8 (�29.0). Patients with preeclampsia tended to have higher LDL levels
compared to patients without preeclampsia (150.2 vs. 129.4). The Mann-Whitney
test shows this difference is statistically significant (p = 0.021).
CONCLUSION
Low levels of placental growth factor (PIGF)
are a risk factor for preeclampsia (OR 4.33; p 0.0302). High levels of soluble
FMS-like Tyrosine Kinase 1 (sFlt-1) are a risk factor for preeclampsia (OR
4.33; p 0.027). A high soluble FMS-like Tyrosine Kinase 1 (sFlt-1) / Placental
Growth Factor (PIGF) ratio is a risk factor for preeclampsia (OR 4.33 p 0.030).
High levels of Low Density Lipoprotein (LDL) are a
risk factor for preeclampsia (OR 6.0; p 0.013).
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