Quick search in Citations
This JournalAnywhereCitation
Advanced Search
Research Article
Originally Published 27 September 2004
Free Access

Short- and Long-Term Changes in Plasma Inflammatory Markers Associated With Preeclampsia

Dilys J. Freeman, Frances McManus, Elizabeth Ann Brown, Lynne Cherry, John Norrie, Jane E. Ramsay, Peter Clark, Isobel D. Walker, Naveed Sattar, and Ian A. GreerAuthor Info & Affiliations
Hypertension
Volume 44, Number 5
https://doi.org/10.1161/01.HYP.0000143849.67254.ca
Track CitationsAdd to favorites
PDF/EPUB

Abstract

Preeclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Low-grade chronic inflammation is a risk factor for cardiovascular disease. This study examined changes in inflammatory markers prospectively during pregnancy, the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls, and the association between inflammatory genes and risk of preeclampsia in a case (n=106) control (n=212) study. In control pregnancies (n=34), mean interleukin-10 (IL-10) levels increased 38% (P=0.012) and tumor necrosis factor-α (TNF-α) by 33% (P=0.024) between the first and third trimesters. The mean preeclampsia group IL-10 and TNF-α rose by 43% (P=0.013 and P=0.0065, respectively) from the first to the third trimester. In women with preeclampsia only, plasma IL-6 increased from the first to the third trimester (1.66 [2.04] to 2.94 [2.47] pg/mL; P=0.0004). Twenty years after the index pregnancy, women who had had preeclampsia demonstrated significantly higher IL-6 to IL-10 ratio (3.96 [6.07] versus 2.12 [1.89]; P=0.034) compared with a healthy index pregnancy 20 years previously, that persisted after adjustment for smoking and current body mass index. The IL-1β (C-511T), IL-6 (G-174C), TNF-α (G-308A), E-selectin (S128R), intercellular adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were not associated with risk of developing preeclampsia. In conclusion, preeclampsia is associated with short- and long-term changes in inflammatory status.
Preeclampsia (PE) is a disorder peculiar to pregnancy1 and a major cause of maternal death and damage to the developing baby. It is characterized by widespread endothelial dysfunction throughout the maternal circulation resulting in hypertension attributable to vasoconstriction, proteinuria attributable to glomerular damage, and edema attributable to an increase in vascular permeability. It has now been shown that PE may herald heart disease later in life for the mother.2,3
The specific factors initiating endothelial damage in PE are unknown, although activation of the coagulation system, platelets, and neutrophils are implicated.1 Normal pregnancy is associated with activation of peripheral blood leukocytes, a response more marked in women with PE.4 Inflammatory cells are activated in PE and localized to the site of vascular injury.5 This white cell activation is associated with higher levels of proinflammatory molecules, cytokines, and adhesion molecules. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) have been shown by ourselves6 and others7,8 to be raised in PE. It has been suggested that PE is attributable to an excessive maternal inflammatory response to pregnancy secondary to a combination of placental factors and maternal factors related to phenotype and genotype.9 This inflammatory response contributes to the wider syndrome of endothelial dysfunction and thrombotic and metabolic disturbances seen in PE.
The parallels between metabolic disturbances in PE and cardiovascular disease (CVD) are striking and may explain the risk of future CVD associated with PE.10 Recently, there has been recognition of the role of inflammation in atherosclerosis.11 Markers of inflammation independently predict CVD events.12 Another common risk factor shared by PE and CVD is obesity.13 Adipose tissue is now recognized as an endocrine organ that secretes a number of active substances including proinflammatory cytokines.14 Adipose tissue produces IL-6 and TNF-α, and these cytokines might contribute to insulin resistance and the resulting dyslipidemia, both features of PE. Variation in genes coding for inflammatory cytokines might be associated with risk of inflammatory disease and atherosclerosis.15–18 However, studies assessing the impact of variation at inflammatory genes on risk of PE are sparse.19–22
The aim of this study was to compare baseline and, prospectively, short-term pregnancy-induced changes in plasma inflammatory markers in women who experienced healthy pregnancies with those whose pregnancy was complicated by PE. In addition, we compared plasma inflammatory markers between women with a healthy pregnancy to those with pregnancy complicated by PE an average of 20 years earlier. Finally, we studied whether variation at genes coding for inflammatory markers is predictive of PE.

Methods

Patient Populations

All patient samples were collected from the same West of Scotland population attending the Princess Royal Maternity Unit at Glasgow Royal Infirmary. Ethical approval was received from the North Glasgow University Hospital National Health Service (NHS) trust research ethics committee, and all women gave informed consent. Women with PE were identified according to criteria defined by the International Society for the Study of Hypertension in Pregnancy (ISSHP) (ie, diastolic blood pressure >110 mm Hg on 1 occasion or >90 mm Hg during repeated readings, with proteinuria ≥0.3 g for 24 hours, or 2+ proteinuria during dipstick testing, without renal disease or infection).

Study 1

Study 1 used samples collected for the Glasgow Outcome, Activated protein-C resistance, and Lipid (GOAL) Pregnancy Study.23 Baseline plasma samples were available from 45 women who subsequently developed PE and from 45 age- and parity-matched controls who experienced no adverse pregnancy outcome. In a subset (n=34 per group), first and third trimester plasma samples were available.

Study 2

Primigravidae delivering between 1975 and 1985 with proteinuric PE in line with the ISSHP criteria and matched controls were identified from medical records as described previously.24

Study 3

By combining available samples of blood cell pellets from studies 1 and 2, plus an additional 21 PE women from study 1 who had blood cells available for DNA extraction but no plasma samples, 106 women with a history of PE from the same West of Scotland population attending the same maternity hospital were identified, each matched for age (±2 years) and parity (0, 1, >1) with 2 control samples.

Biochemical Assays

Plasma IL-6, IL-10, soluble (s) intercellular adhesion molecule-1 (ICAM-1), s vascular cell adhesion molecule-1 (VCAM-1), and TNF-α were measured in citrated plasma stored at −80°C using high-sensitivity commercial ELISA kits (R&D Systems). C-Reactive protein (CRP) was measured using a high-sensitivity, 2-site enzyme-linked immunoassay.25

Polymorphism Detection

DNA was extracted from packed blood cells stored at −80°C.26 Polymorphisms were detected by polymerase chain reaction amplification and digestion with the appropriate restriction enzyme. Methods were as described: CRP G1059C,27 E-selectin S128R,28 ICAM-1 K469E,29 IL-1β C-511T,30 IL-6 G-174C, 31 and TNF-α G-308A.30

Statistical Analysis

Baseline (first trimester) characteristics were tabulated and compared between the PE and control groups using 2-sample t tests for continuous data or χ2 tests (or Fisher exact tests) for categorical data. For some of the skewed continuous variates, data were log transformed. For IL-10, which had some zeroes, the Wilcoxon rank sum test was used. For the ratio of IL-6 to IL-10, a zero IL-10 was ranked highest, and a Wilcoxon rank sum test was used. Within a group (either PE or controls), changes at third trimester over first trimester (baseline) were compared using paired 1-sample t tests, and then these differences between trimesters were compared between groups using 2-sample t tests. Throughout, all the estimated differences were then adjusted for important covariates, such as smoking, body mass index (BMI), gestational age, and menopausal status using normal linear models. The influence of the various genotypes was investigated using conditional logistic regression, with strata of age crossed with parity, with an additional term to adjust for study. Odds ratios with 95% confidence intervals and associated P values are reported. All analyses were performed in SAS 8.2 for Windows. No adjustments have been made for multiple comparisons.

Results

Study 1: Baseline Plasma Inflammatory Markers

Baseline characteristics for study 1 are shown in Table 1. There were no significant differences in booking BMI, Carstairs social deprivation category,32 twin pregnancies, and gestational age at sampling. As expected, the PE group had a trend toward higher baseline diastolic blood pressure, had significantly fewer smokers (P=0.021), and delivered babies of lower birth weight centile (mean [SD] control 52.3 [31.3] versus PE 33.2 [26.5]; P=0.0026). There were no significant differences in baseline plasma IL-10, IL-6/IL-10 ratio, sICAM-1, sVCAM-1, CRP, or TNF-α levels between control women and women who subsequently developed PE. Women with a PE pregnancy had a tendency to higher plasma IL-6 levels than age- and parity-matched healthy pregnancy women (control 1.19 [0.70] versus PE 1.58 [1.79] pg/mL; P=0.051). This difference in IL-6 was independent of smoking (P=0.052) but was attenuated on adjusting for smoking and booking BMI (least squares mean [SEM] in controls 1.20 [0.23] versus PE 1.56 [0.28] pg/mL; P=0.26).
TABLE 1. Baseline Characteristics for Study 1
CharacteristicControlPEP Value
No.StatisticNo.Statistic
Data shown mean (SD) for continuous measurements and for categorical covariates number of subjects (%).
*Two-sample ttests on log-transformed data.
†Wilcoxon rank sum test.
Age (years)4529.3 (4.6)4529.4 (4.7)0.98
>0 live birth4514 (31%)4514 (31%)1.00
>0 unsuccessful pregnancy4512 (27%)4514 (31%)0.82
Booking BMI (kg/m2)4424.4 (4.4)3725.6 (4.1)0.23
Systolic blood pressure (mm Hg)45110.2 (11.6)44113.8 (9.6)0.12
Diastolic blood pressure (mm Hg)4566.7 (9.0)4470.3 (8.9)0.062
Smoking4519 (42%)438 (19%)0.021
Deprivation category40 43 0.48
    1–2 10 (25%) 7 (16%) 
    3–5 16 (40%) 16 (37%) 
    6–7 14 (35%) 20 (47%) 
% twin pregnancy450 (0%)452 (4%)0.49
Gestation PE onset (weeks)——4535.2 (3.5)—
Birth weight centile4452.3 (31.3)4533.2 (26.5)0.0026
Gestation at sampling (weeks)4510.6 (2.3)4510.8 (2.2)0.64
IL-6 (pg/mL)*431.19 (0.70)451.58 (1.79)0.051
IL-10 (pg/mL)*421.77 (1.58)451.92 (1.53)0.29
IL-6/IL-10 ratio*413.98 (6.76)453.03 (6.00)0.85†
sICAM-1 (ng/mL)45187 (56)45187 (75)0.98
sVCAM-1 (ng/mL)45311 (88)45289 (61)0.18
CRP (mg/L)*453.18 (2.60)454.18 (3.75)0.23
TNF-α (pg/mL)*441.88 (2.04)451.40 (1.17)0.69

Study 1: Third Trimester Inflammatory Markers

Third trimester inflammatory markers were available in a subset of 34 individuals from study 1 (Table 2). There were significantly higher levels of IL-6 (controls 1.47 [0.88] versus PE 2.94 [2.47]; P<0.0001) and CRP (controls 3.34 [3.40] versus PE 5.84 [5.38]; P=0.0091) in third trimester PE women compared with control women. The difference in IL-6 was independent of booking BMI, smoking, and gestational age at third trimester combined (P=0.0052). However, the difference in CRP was independent of smoking (P=0.0062) but is attenuated by booking BMI plus smoking (P=0.063) and further by booking BMI, smoking, and gestational age at third trimester (P=0.14).
TABLE 2. First and Third Trimester Inflammatory Markers in Study 1
ParameterControl (No.=34)T1 vs T3PE (No.=34)T1 vs T3Control (T3) vs PE (T3)
T1T3PT1T3PP
Data shown mean (SD) for first trimester (T1) and third trimester (T3), with 1-sample ttest Pvalue for test of difference between first and third trimester within each group and 2-sample ttest Pvalue for test of difference between control and PE third trimester samples.
* Wilcoxon test.
Gestational age (weeks)10.5 (2.4)31.0 (3.3)N/A10.7 (2.2)29.5 (2.4)N/A0.033
IL-6 (pg/mL)1.21 (0.77)1.47 (0.88)0.211.66 (2.04)2.94 (2.47)0.0004<0.0001
IL-10 (pg/mL)1.83 (1.66)2.52 (2.08)0.0121.80 (1.62)2.57 (1.88)0.0130.68
IL-6/IL-10 ratio4.30 (7.14)3.04 (5.82)0.343.78 (6.75)2.81 (4.36)0.470.066*
sICAM-1 (ng/mL)193 (61)187 (42)0.42197 (83)201 (60)0.730.27
sVCAM-1 (ng/mL)292 (62)274 (58)0.19288 (65)289 (75)0.910.35
CRP (mg/L)3.09 (2.59)3.34 (3.40)0.644.16 (3.60)5.84 (5.38)0.090.0091
TNF-α (pg/mL)2.06 (2.21)2.73 (3.00)0.0241.56 (1.21)2.23 (2.19)0.00650.44

Study 1: First to Third Trimester Changes in Inflammatory Markers

First and third trimester samples were available for plasma inflammatory markers in 34 individuals (Table 2). In PE and control groups, plasma IL-10 and TNF-α levels were increased significantly between first and third trimesters. However, these differences were not independent of smoking and booking BMI. Plasma IL-6 levels were significantly increased between the first and third trimester in the PE group but not the control group, and this difference was unaffected by smoking (P=0.0012) but was attenuated by the inclusion of BMI (P=0.046). When the mean change in inflammatory markers between first and third trimester was compared (Table 3), plasma IL-6 showed a significantly larger change in PE (77%) compared with controls (21%) (control mean change 0.25 [1.14] versus PE 1.29 [1.91] pg/mL; P=0.0091). This difference in T1 to T3 IL-6 was independent of smoking (adjusted P=0.0071) but not when additionally adjusting for BMI (P=0.20).
TABLE 3. Mean Change (SD) in First Trimester (T1) to Third Trimester (T3) Inflammatory Markers in Study 1
ParameterT1 to T3 Change ControlT1 to T3 Change PEP
Two-sample ttest P values for test of difference between control and PE changes are shown.
IL-6 (pg/mL)0.25 (1.14)1.29 (1.91)0.0091
IL-10 (pg/mL)0.69 (1.48)0.77 (1.71)0.53
IL-6/IL-10 ratio−1.3 (7.4)−1.0 (7.8)0.88
sICAM-1 (ng/mL)−5 (39)4 (67)0.48
sVCAM-1 (ng/mL)−18 (77)2 (81)0.31
CRP (mg/L)0.25 (3.06)1.69 (5.53)0.19
TNF-α (pg/mL)0.66 (1.63)0.68 (1.36)0.97

Study 2: Inflammatory Markers 20 Years After Pregnancy

Study 2 characteristics are shown in Table 4. Cases and controls were selected to match, as a group, for current age and BMI. All women at index pregnancy were primigravid. PE women at index pregnancy had significantly higher BMI, lower birth weight centile, and lower gestation at delivery. At recall, there were no significant differences in parity and smoking between the control and PE groups. Although more PE women were in menopause at recall, this was not a significant difference. There was a significantly higher IL-6/IL-10 ratio, an index of proinflammatory cytokine (IL-6) status to anti-inflammatory cytokine (IL-10) status, in the PE women compared with matched controls (PE 3.96 [6.07] versus control 2.12 [1.89]; P=0.034), independent of smoking, current BMI, and menopause status (P=0.03). Plasma sICAM-1 and sVCAM-1 were also higher in PE women, as we have described previously,24 differences that were also independent of smoking, current BMI, and menopause status.
TABLE 4. Baseline Characteristics for Study 2
CharacteristicControlPEP Value
No.StatisticNo.Statistic
Data shown mean (SD) for continuous measurements, number of subjects (%) for categorical covariates.
*Two-sample ttests on log-transformed data;
†Wilcoxon rank sum test;
‡Data published previously.24
Index pregnancy characteristics     
    Age at pregnancy (years)3924.7 (3.9)4024.9 (5.2)0.92
        >0 live birth390 (0%)400 (0%)—
        >0 unsuccessful pregnancy391 (3%)454 (10%)0.36
    Booking BMI (kg/m2)3321.4 (1.9)3723.1 (3.70)0.014
    Smoking3911 (28%)4010 (25%)0.80
    Deprivation category     
        1–24012 (30%)3811 (29%)0.49
        3–5 18 (45%) 13 (34%) 
        6–7 10 (25%) 14 (37%) 
    Birth weight centile3456.1 (33.1)3632.9 (32.1)0.0041
    Gestation at delivery (weeks)3939.1 (2.8)4035.3 (3.8)<0.0001
Recall characteristics     
    Current age (years)4044.5 (3.1)4044.7 (5.8)0.85
    Time elapsed since index pregnancy (years)3819.8 (3.8)4019.9 (3.2)0.94
    Current BMI (kg/m2)3826.3 (4.0)4027.0 (5.0)0.50
    Parity n (%) 13810 (26%)4012 (30%)0.92
        2 16 (42%) 16 (40%) 
        >2 12 (32%) 12 (30%) 
    Systolic blood pressure (mm Hg)38118.8 (17.2)40124.4 (14.6)0.12
    Diastolic blood pressure (mm Hg)3877.1 (11.5)4081.3 (10.4)0.097
    Smoking n (%)396 (15%)409 (23%)0.57
    Menopause n (%)397 (18%)4015 (38%)0.078
Recall inflammatory markers     
    IL-6 (pg/mL)*402.06 (1.26)402.69 (2.56)0.34
    IL-10 (pg/mL)*402.52 (7.77)401.19 (1.22)0.073†
    IL-6/IL-10 ratio*402.12 (1.89)403.96 (6.07)0.034
    sICAM-1 (ng/mL)‡37271 (116)40354 (143)0.0066
    sVCAM-1 (ng/mL)‡37348 (86)40408 (137)0.023
    CRP (mg/L)*401.66 (1.58)403.04 (4.21)0.26
    TNF-α (pg/mL)*401.07 (0.69)401.16 (0.90)0.97

Study 3: Genetic Predictors of PE

For study 3 characteristics, please see supplemental Table I, available online at http://www.hypertensionaha.org. Cases and controls were matched for age and parity. PE cases had higher BMI and fewer smokers than the controls. Birth weight centile was significantly lower in the PE women, and there was a greater incidence of twin pregnancies in this group. The rare allele frequencies for CRP G1059C, E-selectin S128R, ICAM-1 K469E, IL-1β C-511T, IL-6 G-174C, and TNF-αG-308A polymorphisms were 0.06, 0.08, 0.42, 0.36, 0.41, and 0.22, respectively. Genotype frequencies in the total group, cases, and controls were in Hardy-Weinberg equilibrium for each of the polymorphisms and are shown in Table 5. There was no significant association between any inflammatory gene polymorphisms studied and risk of developing PE.
TABLE 5. Genotype Frequencies of Polymorphisms at Inflammatory Genes in Cases and Controls; Univariate Analysis
FrequencyNo. (%)Univariate Analysis
ControlCaseOdds RatioConfidence IntervalPvalue
CRP C1059G     
    GG185 (8.1)92 (90.2)1.00  
    CG25 (1.9)10 (9.8)0.760.34 to 1.700.50
E-selectin S128R     
    AA181 (85.4)84 (81.6)1.00  
    AA/CC31 (14.6)19 (18.4)1.360.70 to 2.640.37
ICAM-1 K469E     
    AA68 (33.3)31 (33.0)1.00  
    AG104 (51.0)44 (46.8)1.060.59 to 1.920.84
    GG32 (15.7)19 (20.2)1.300.62 to 2.740.49
IL-1β C-511T     
    CC89 (42.0)50 (47.2)1.00  
    CT91 (42.9)40 (37.7)0.810.48 to 1.380.44
    TT32 (15.1)16 (15.1)0.790.38 to 1.640.53
IL-6 G-174C     
    GG70 (33.0)44 (41.5)1.00  
    CG103 (48.6)46 (43.4)0.710.41 to 1.220.21
    CC39 (18.4)16 (15.1)0.570.28 to 1.190.13
TNF-α G-308A     
    GG133 (63.0)62 (58.5)1.00  
    AA/AG78 (37.0)44 (41.5)1.250.76 to 2.080.38

Discussion

In our prospective study, baseline IL-6 levels had a tendency to be higher in women who subsequently develop PE. However, this was not independent of BMI and may reflect the role of BMI as a risk factor for PE. In control and PE pregnant women, plasma IL-10 and TNF-α increased from first to third trimester and may represent the normal inflammatory response of pregnancy with changes in proinflammatory and anti-inflammatory markers. These changes were no longer apparent after accounting for smoking habit and BMI, and thus the degree of inflammatory response to the physiological stress of pregnancy may be influenced by maternal adiposity and smoking status. Interestingly, plasma IL-6 levels were only increased during pregnancy in women who developed PE, and this increase, although attenuated, persisted after correction for booking BMI, suggesting that increases in IL-6 may be specific to PE and are not entirely determined by maternal adiposity. Thus, inflammatory pathways involving IL-6 may be involved in the etiology of PE in keeping with previous reports from cross-sectional studies. It is possible that women with other related disorders of pregnancy such as pregnancy-induced hypertension, diabetes, and intrauterine growth restriction may also show increases in plasma IL-6. Further studies should be performed in these groups to exclude this possibility.
In other prospective studies, first trimester TNF-α was significantly higher in women who subsequently developed PE compared with those who did not.33,34 However, these studies did not account for BMI. Djurovic et al35 found no differences in IL-6 at 18-week gestation between women who subsequently developed PE and healthy control women when BMI was accounted for. This may suggest that an increase in IL-6 occurs later than this gestation. Many, although not all, studies have identified higher third trimester plasma levels of IL-6 and TNF-α in PE women. However, only 1 study has accounted for the influence of BMI36 and did confirm raised levels of these cytokines. In that study, a significant correlation between maternal serum leptin and TNF-α concentration was found underlining the association between fat mass and inflammatory cytokine production. Third trimester plasma IL-10 levels are reported as higher37 and lower38 in PE compared with control pregnancies, although in both studies, BMI was not accounted for, and in the latter study, it is not clear that cases and controls were matched for gestational age at sampling. Thus, because maternal adipose tissue may contribute to plasma levels of TNF-α and IL-10, and because plasma TNF-α and IL-10 increase in normal pregnancy, failure of other studies to account for BMI and gestational age at sampling may explain differences between studies.
Our data confirm those of other groups that observed higher IL-6 at third trimester in PE6–8,36 but not when BMI was taken into account.35 The source of the IL-6 is important because these data suggest that total obesity alone does not fully explain these findings. Plasma IL-6 in pregnancy may be derived from adipose tissue (and adipose mass can be different in women of similar BMI), placenta, and circulating lymphocytes. Other researchers have been unable to identify increased IL-6 production by the placenta in PE.39,40 Endothelial cells41 have been demonstrated to have increased IL-6 production in severe PE. Another possibility is that adipose tissue mass per se is not important, rather adipose tissue functionality. It is possible that PE women have much more “active” adipose tissue (eg, greater lipolytic rates leading to increased plasma free fatty acid concentrations and greater synthesis and secretion of adipokines). Maternal adipose tissue functionality in PE has not been studied. Correcting for the influence of smoking increases the disparity between control and PE women. This is attributable to the higher number of smoking individuals in the control group allied to the known link between smoking and higher background level of inflammatory markers. It is unlikely that IL-6 is responsible for the entire maternal metabolic syndrome of PE, but it could accentuate aspects of the response (eg, insulin resistance42 and endothelial dysfunction43). Establishing which tissue(s) contributes to the increase in plasma IL-6 might help address some of these issues.
The retrospective study assessing inflammatory markers in women 20 years after the index pregnancy investigated whether short-term inflammatory changes seen during pregnancy are retained later in life. There was a trend toward decreased IL-10, an anti-inflammatory cytokine, in women with a history of PE and a significantly higher IL-6 to IL-10 ratio that was independent of smoking, current BMI, and menopause status. Thus, the higher inflammatory status of women with a history of PE does not merely reflect a higher BMI.
Our group has shown that sICAM-1 and sVCAM-1 were raised in women with a history of PE 20 years previously,24 and the data are re-presented in Table 4. These inflammatory markers are, to some degree, thought to reflect endothelial dysfunction. Thus, their elevation in women with a history of PE may indicate a greater degree of endothelial dysfunction in these women. It is noteworthy that although the endothelial function markers, sICAM-1 and sVCAM-1, were raised in women with a previous history of PE, these markers were not elevated during pregnancy in PE. It is possible that the acute inflammatory response seen during pregnancy in PE indicates a woman’s innate susceptibility to inflammation but is not sufficient to provoke all the endothelial changes associated with chronic exposure to vascular risk factors over a number years. Our group has reported that PE women have significantly impaired endothelial function compared with controls.44 ICAM-1 and VCAM-1 are upregulated in atherosclerosis and may act as markers for the disease. However, evidence from knockout mice indicates that VCAM-1 plays a dominant role in the initiation of atherosclerosis and is important for the disease pathway.45 The raised sVCAM-1 levels, IL-6/IL-10 ratio, and endothelial dysfunction in combination with a higher level of inflammatory response seen in subjects with PE in our study would help explain why women with a history of PE are at increased risk of CVD. Thus, PE and CVD share common proinflammatory risk factors.
In this study, we were unable to find any significant contribution of variation at CRP, E-selection, ICAM-1, IL-β, IL-6, or TNF-α genes to risk of PE in this West of Scotland population despite their contribution to other inflammatory disease.15–18 The current study was powered to detect a 2-fold increase in risk and would not have identified any smaller increases. Other studies have found contributions of TNF-α to PE,19–21 but these observations have not been confirmed by others,22,46 including a large family study.47 PE is a multifactorial disorder with an imprecise definition, and it likely has a complex and varied etiology with interaction between placental factors and maternal phenotypes and genotype being responsible for the clinical expression of this condition. Many genes, maternal and fetal, interacting with each other and a variety of environmental stimuli may therefore contribute to disease severity and outcome. Until large, well-defined PE populations are available for study, it is unlikely that genetic variants that consistently and significantly contribute to disease will be found.

Perspectives

This study suggests that susceptibility to inflammation might be a common underlying risk factor for PE and CVD. It will be important to establish whether susceptibility to inflammation is specific to PE or underlies other common disorders of pregnancy also linked to future CVD such as intrauterine growth restriction and preterm delivery. The mechanism for this inflammatory susceptibility is unknown and could be attributable to a generalized upregulation of a number of inflammatory processes or could be a specific overactivity of a particular tissue such as adipose tissue. An understanding of the genetic and metabolic mechanisms involved may inform strategies for identification and intervention in individuals at risk.

Acknowledgments

Tenovus Scotland (grant reference S00/9) and the University of Glasgow Medical Research Funds Committee are gratefully acknowledged for their support.

Supplemental Material

File (2731.doc)

References

1.
Lyall F, Greer IA. Preeclampsia: a multifaceted vascular disorder of pregnancy. J Hypertens. 1994; 12: 1339–1345.
PubMed
Google Scholar
2.
Smith GC, Pell JP, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129 290 births. Lancet. 2001; 357: 2002–2006.
Crossref
PubMed
Google Scholar
3.
Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long term mortality of mothers and fathers after preeclampsia: population-based cohort study. BMJ. 2001; 323: 1213–1217.
Crossref
PubMed
Google Scholar
4.
Sacks GP, Studena K, Sargent IL, Redman CWG. Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. Am J Obstet Gynecol. 1998; 179: 80–86.
Crossref
PubMed
Google Scholar
5.
Lyall F, Greer IA, Boswell F, Macara LM, Walker JJ, Kingdom JC. The cell adhesion molecule, VCAM-1, is selectively elevated in serum in preeclampsia: does this indicate the mechanism of leucocyte activation? BJOG. 1994; 101: 173–174.
Google Scholar
6.
Greer IA, Lyall F, Perera T, Boswell F, Macara LM. Increased concentrations of cytokines IL-6 and IL-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction? Obstet Gynecol. 1994; 84: 937–940.
PubMed
Google Scholar
7.
Conrad KP, Miles TM, Benyo DF. Circulating levels of immunoreactive cytokines in women with preeclampsia. Am J Reprod Immunol. 1998; 40: 102–111.
Crossref
PubMed
Google Scholar
8.
Vince GS, Starkey PM, Austgulen R, Kwiatkowski D, Redman CW. IL-6, tumour necrosis factor and soluble tumour necrosis factor receptors in women with preeclampsia. BJOG. 1995; 102: 20–25.
Crossref
Google Scholar
9.
Redman CWG, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. AJOG. 1999; 180: 499–506.
Crossref
PubMed
Google Scholar
10.
Rodie VA, Freeman DJ, Sattar N, Greer IA. Preeclampsia and cardiovascular disease: metabolic syndrome of pregnancy? Atherosclerosis. 2004; 175: 189–202.
Crossref
PubMed
Google Scholar
11.
Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med. 1999; 340: 115–126.
Crossref
PubMed
Google Scholar
12.
Blake GJ, Ridker PMJ. Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med. 2002; 252: 283–294.
Crossref
PubMed
Google Scholar
13.
Sattar N, Clark P, Holmes A, Lean ME, Walker I, Greer IA. Antenatal waist circumference and hypertension risk. Obstet Gynecol. 2001; 97: 268–271.
PubMed
Google Scholar
14.
Wolf M, Kettyle E, Sandler L, Ecker JL, Roberts J, Thadhani R. Obesity and preeclampsia: the potential role of inflammation. Obstet Gynecol. 2001; 98: 757–762.
Crossref
PubMed
Google Scholar
15.
Brull DJ, Serrano N, Zito F, Jones L, Montgomery HE, Rumley A, Sharma P, Lowe GD, World MJ, Humphries SE, Hingorani AD. Human CRP gene polymorphism influences CRP levels. Implications for the prediction and pathogenesis of coronary heart disease. Arterioscler Thromb Vasc Biol. 2003; 23: 1–7.
Crossref
PubMed
Google Scholar
16.
Jiang H, Klein RM, Niederacher D, Du M, Marx R, Horlitz M, Boerrigter G, Lapp H, Scheffold T, Krakau I, Gulker H. C/T polymorphism of the intercellular adhesion molecule-1 gene (exon 6, codon 469). A risk factor for coronary heart disease and myocardial infarction. Int J Cardiol. 2002; 84: 171–177.
Crossref
PubMed
Google Scholar
17.
Humphries SE, Luong LA, Ogg MS, Hawe E, Miller GJ. The IL-6–174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J. 2001; 22: 2243–2252.
Crossref
PubMed
Google Scholar
18.
Vatay A, Bene L, Kovacs A, Prohaszka Z, Szalai C, Romics L, Fekete B, Karadi I, Fust G. Relationship between the tumour necrosis factor alpha polymorphism and the serum C-reactive protein levels in inflammatory bowel disease. Immunogenetics. 2003; 55: 247–252.
Crossref
PubMed
Google Scholar
19.
Heiskanen J, Romppanen EL, Hiltunen M, Iivonen S, Mannermaa A, Punnonen K, Heinonen S. Polymorphism in the tumor necrosis factor-alpha gene in women with preeclampsia. J Assist Reprod Genet. 2002; 19: 220–223.
Crossref
PubMed
Google Scholar
20.
Lachmeijer AM, Nosti-Escanilla MP, Bastiaans EB, Pals G, Sandkuijl LA, Kostense PJ, Aarnoudse JG, Crusius JB, Pena AS, Dekker GA, Arngrimsson R, ten Kate LP. Linkage and association studies of IL1B and IL1RN gene polymorphisms in preeclampsia. Hypertens Pregnancy. 2002; 21: 23–38.
Crossref
PubMed
Google Scholar
21.
Chen G, Wilson R, Wang SH, Zheng HZ, Walker JJ, McKillop JH. Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in preeclampsia. Clin Exp Immunol. 1996; 104: 154–159.
Crossref
PubMed
Google Scholar
22.
Dizon-Townson DS, Major H, Ward K. A promoter mutation in the tumour necrosis factor α gene is not associated with preeclampsia. J Reprod Immunol. 1998; 38: 55–61.
Crossref
PubMed
Google Scholar
23.
Clark P, Sattar N, Walker ID, Greer IA. The Glasgow Outcome, APCR and Lipid (GOAL) Pregnancy Study: significance of pregnancy associated activated protein C resistance. Thromb Haemost. 2001; 85: 30–35.
Crossref
PubMed
Google Scholar
24.
Sattar N, Ramsay J, Crawford L, Cheyne H, Greer IA. Classical and novel risk factor parameters in women with a history of preeclampsia. Hypertension. 2003; 42: 39–42.
Crossref
PubMed
Google Scholar
25.
Packard CJ, O’Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J, Macphee CH, Suckling KE, Krishna M, Wilkinson FE, Rumley A, Lowe GD. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med. 2000; 343: 1148–1155.
Crossref
PubMed
Google Scholar
26.
Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones HW Jr, Rary JM. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977; 74: 1245–1249.
Crossref
PubMed
Google Scholar
27.
Cao H, Hegele RA. Human C-reactive protein (CRP) 1059G/C polymorphism. J Hum Genet. 2000; 45: 100–101.
Crossref
PubMed
Google Scholar
28.
Ye SQ, Usher D, Virgil D, Zhang LQ, Yochim SE, Gupta R. A PstI polymorphism detects the mutation of serine 128 to arginine in CD 62E gene –a risk factor for coronary artery disease. J Biomed Sci. 1999; 6: 18–21.
PubMed
Google Scholar
29.
Nejentsev S, Laine A, Simell O, Ilonen J. Intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism: no association with type 1 diabetes among Finns. Tissue Antigens. 2000; 55: 568–570.
Crossref
PubMed
Google Scholar
30.
Mansfield JC, Holden H, Tarlow JK, Di Giovine fractional shortening (FS), McDowall TL, Wilson AG, Holdsworth CD, Duff GW. Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine IL-1 receptor antagonist. Gastroenterology. 1994; 106: 637–642.
Crossref
PubMed
Google Scholar
31.
Fishman D, Faulds G, Jeffrey R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P. The effect of novel polymorphisms in the IL 6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998; 102: 1369–1376.
Crossref
PubMed
Google Scholar
32.
Carstairs V, Morris R. Deprivation and mortality: an alternative to social class? Community Med. 1989; 11: 210–219.
PubMed
Google Scholar
33.
Hamai Y, Fujii T, Yamashita T, Nishina H, Kozuma S, Mikami Y and Taketani Y. Evidence for an elevation in serum IL-2 and tumour necrosis factor-alpha levels before the clinical manifestations of preeclampsia. Am J Reprod Immunol. 1997; 38: 89–93.
Crossref
PubMed
Google Scholar
34.
Omu AE, Al-Qattan F, Diejomach ME, Al-Yatama M. Differential levels of T helper cytokines in preeclampsia: pregnancy, labor and puerperium. Acta Obstet Gynecol Scand. 1999; 78: 675–680.
Crossref
PubMed
Google Scholar
35.
Djurovic S, Clausen T, Wergeland R, Brosstad F, Berg K, Henriksen T. Absence of enhanced systemic inflammatory response at 18 weeks of gestation in women with subsequent preeclampsia. BJOG. 2002; 109: 759–764.
Crossref
PubMed
Google Scholar
36.
Bartha JL, Romero-Carmona R, Escobar-Llompart M, Comino-Delgado R. The relationships between leptin and inflammatory cytokines in women with preeclampsia. BJOG. 2001; 108: 1272–1276.
PubMed
Google Scholar
37.
Benian A, Madazh R, Aksu F, Uzun H, Aydun S. Plasma and placental levels of IL-10, transforming growth factor-β1, and epithelial-cadherin in preeclampsia. Obstet Gynecol. 2002; 100: 327–331.
PubMed
Google Scholar
38.
Hennessy A, Pilmore HL, Simmons LA, Painter DM. A deficiency of placental IL-10 in preeclampsia. J Immunol. 1999; 163: 3491–3495.
Crossref
PubMed
Google Scholar
39.
Benyo DF, Smarason A, Redman CW, Sims C, Conrad K. Expression of inflammatory cytokines in placentas from women with preeclampsia. J Clin Endocrinol Metab. 2001; 86: 2505–2512.
PubMed
Google Scholar
40.
Kauma SW, Wang Y, Walsh SW. Preeclampsia is associated with decreased placental IL-6 production. J Soc Gynecol Investig. 1995; 2: 614–617.
PubMed
Google Scholar
41.
Takacs P, Green KL, Nikaeo A, Kauma SW. Increased vascular endothelial cell production of IL-6 in severe preeclampsia. Am J Obstet Gynecol. 2003; 188: 740–744.
Crossref
PubMed
Google Scholar
42.
Temelkova-Kurktschiev T, Siegert G, Bergmann S, Henkel E, Koehler C, Jaro W, Hanefeld M. Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes. Metabolism. 2002; 51: 743–749.
Crossref
PubMed
Google Scholar
43.
Cleland SJ, Sattar N, Petrie JR, Forouhi NG, Elliott HL, Connell JMC. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin Sci. 2000; 98: 531–535.
Crossref
PubMed
Google Scholar
44.
Ramsay JE, Stewart F, Greer IA, Sattar N. Microvascular dysfunction: a link between preeclampsia and maternal coronary heart disease. BJOG. 2003; 110: 1029–1031.
Crossref
PubMed
Google Scholar
45.
Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos J-C, Connelly PW, Milstone DS. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest. 2001; 107: 1255–1262.
Crossref
PubMed
Google Scholar
46.
Livingston JC, Park V, Barton JR, Elfering S, Haddad B, Mabie WC, Quasney M, Sibai BM. Lack of association of severe preeclampsia with maternal and fetal mutant alleles for tumour necrosis factor α and lymphotoxin α genes and plasma tumor necrosis factor α levels. Am J Obstet Gynecol. 2001; 184: 1273–1277.
Crossref
PubMed
Google Scholar
47.
Lachmeijer AMA, Crusius JBA, Pals G, Dekker GA, Arngrimsson R, Kate LPT. Polymorphisms in the tumour necrosis factor and lymphotoxin-α gene region and preeclampsia. Obstet Gynecol. 2001; 98: 612–619.
PubMed
Google Scholar

eLetters(0)

eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.

Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.

Sign In to Submit a Response to This Article

Information & Authors

Information

Published In

Go to Hypertension
Go to Hypertension
Hypertension
Volume 44 • Number 5 • 1 November 2004
Pages: 708 - 714
PubMed: 15452036

Copyright

© 2004.

Versions

You are viewing the most recent version of this article.

History

Received: 14 May 2004
Revision received: 8 June 2004
Accepted: 24 August 2004
Published online: 27 September 2004
Published in print: 1 November 2004

Permissions

Request permissions for this article.

Keywords

  1. preeclampsia
  2. polymorphism
  3. cardiovascular diseases
  4. inflammation

Authors

Affiliations

Dilys J. Freeman
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
Frances McManus
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
Elizabeth Ann Brown
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
Lynne Cherry
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
John Norrie
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
Jane E. Ramsay
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
Peter Clark
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
Isobel D. Walker
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
Naveed Sattar
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author
Ian A. Greer
From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.
View all articles by this author

Notes

Correspondence to Dr Dilys Freeman, Division of Developmental Medicine, Third Floor Queen Elizabeth Building, Royal Infirmary, 10 Alexandra Parade, Glasgow, G31 2ER, UK. E-mail [email protected]

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

    • Muhammad Naveed Najeeb,
    • Umaira Munir,
    • Muhammad Ameer Hamza,
    • Sadia Mehmood,
    • Javed Anver Qureshi,
    • Tahir Maqbool,
    Interleukin-6 (-174G/C), Interleukin-1β (-511 C/T), and Apolipoprotein B-100 (2488 C/T) Gene Polymorphism in Pre-Eclampsia, Medicina, 60, 8, (1307), (2024).https://doi.org/10.3390/medicina60081307
    Crossref
    • Maja Gajić,
    • Bianca Schröder-Heurich,
    • Karoline Mayer-Pickel,
    Deciphering the immunological interactions: targeting preeclampsia with Hydroxychloroquine’s biological mechanisms, Frontiers in Pharmacology, 15, (2024).https://doi.org/10.3389/fphar.2024.1298928
    Crossref
    • Nakeisha A. Lodge‐Tulloch,
    • Jean‐François Paré,
    • Camille Couture,
    • Elsa Bernier,
    • Tiziana Cotechini,
    • Sylvie Girard,
    • Charles H. Graham,
    Maternal Innate Immune Reprogramming After Complicated Pregnancy, American Journal of Reproductive Immunology, 92, 2, (2024).https://doi.org/10.1111/aji.13908
    Crossref
    • Yuhong Hu,
    • Thomas Chavez,
    • Sandrah P. Eckel,
    • Tingyu Yang,
    • Xinci Chen,
    • Mario Vigil,
    • Nathan Pavlovic,
    • Fred Lurmann,
    • Deborah Lerner,
    • Nathana Lurvey,
    • Brendan Grubbs,
    • Laila Al-Marayati,
    • Claudia Toledo-Corral,
    • Jill Johnston,
    • Genevieve F. Dunton,
    • Shohreh F. Farzan,
    • Rima Habre,
    • Carrie Breton,
    • Theresa M. Bastain,
    Joint effects of traffic-related air pollution and hypertensive disorders of pregnancy on maternal postpartum depressive and anxiety symptoms, Journal of Exposure Science & Environmental Epidemiology, (2024).https://doi.org/10.1038/s41370-024-00692-9
    Crossref
    • Md. Shafiul Hossen,
    • Md. Abdul Aziz,
    • Md Abdul Barek,
    • Mohammad Safiqul Islam,
    Investigation of the linkage between TNF-alfa rs1800629 polymorphism and preeclampsia risk: A meta-analysis, Cytokine, 175, (156499), (2024).https://doi.org/10.1016/j.cyto.2024.156499
    Crossref
    • Lidia Boldeanu,
    • Constantin-Cristian Văduva,
    • Daniel Cosmin Caragea,
    • Marius Bogdan Novac,
    • Mariana Manasia,
    • Isabela Siloși,
    • Maria Magdalena Manolea,
    • Mihail Virgil Boldeanu,
    • Anda Lorena Dijmărescu,
    Association between Serum 8-Iso-Prostaglandin F2α as an Oxidative Stress Marker and Immunological Markers in a Cohort of Preeclampsia Patients, Life, 13, 12, (2242), (2023).https://doi.org/10.3390/life13122242
    Crossref
    • Tatjana Maselienė,
    • Emilija Struckutė,
    • Rūta Breivienė,
    • Diana Ramašauskaitė,
    • Vilma Dženkevičiūtė,
    The Importance of Inflammatory and Angiogenic Markers in the Evaluation of Early Cardiovascular Disease Risk in Women with Hypertensive Disorders of Pregnancy, Journal of Cardiovascular Development and Disease, 10, 10, (407), (2023).https://doi.org/10.3390/jcdd10100407
    Crossref
    • Samprikta Manna,
    • Colm J. Mc Elwain,
    • Gillian M. Maher,
    • Marta Giralt Martín,
    • Andrea Musumeci,
    • Fergus P. McCarthy,
    • Cathal McCarthy,
    Heterogenous Differences in Cellular Senescent Phenotypes in Pre-Eclampsia and IUGR following Quantitative Assessment of Multiple Biomarkers of Senescence, International Journal of Molecular Sciences, 24, 4, (3101), (2023).https://doi.org/10.3390/ijms24043101
    Crossref
    • Alina-Georgiana Corduneanu,
    • Ioana Păvăleanu,
    • Mihai Emil Capilna,
    Inflammation, Gestational Hypertension, and Preeclampsia – a Dangerous Association, Journal of Cardiovascular Emergencies, 9, 1, (1-8), (2023).https://doi.org/10.2478/jce-2023-0002
    Crossref
    • Malamo E. Countouris,
    • Agnes Koczo,
    • Harmony R. Reynolds,
    • Anais Hausvater,
    • Harnoor Mann,
    • Yisi Wang,
    • Danielle Sharbaugh,
    • Floyd W. Thoma,
    • Suresh R. Mulukutla,
    • Janet M. Catov,
    Characteristics of Premature Myocardial Infarction Among Women With Prior Adverse Pregnancy Outcomes, JACC: Advances, 2, 5, (100411), (2023).https://doi.org/10.1016/j.jacadv.2023.100411
    Crossref
  11. See more

View Options

View options

PDF and All Supplements

Download PDF and All Supplements

PDF/EPUB

View PDF/EPUB
Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Save for later Item saved, go to cart
Purchase Options

Purchase this article to access the full text.

Purchase access to this article for 24 hours

Short- and Long-Term Changes in Plasma Inflammatory Markers Associated With Preeclampsia
Hypertension
  • Vol. 44
  • No. 5

Purchase access to this journal for 24 hours

Hypertension
  • Vol. 44
  • No. 5
Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

Media

Figures

Other

Tables

Share

Share

Share article link

Share

View full text|Download PDF

Comment Response