Preeclamptic Women Research Articles

Predictive and diagnostic value of serum sVEGFR-1 level in women with preeclampsia: A prospective controlled study.

Pre-eclampsia (PE), a pregnancy-specific syndrome consisting of hypertension and proteinuria occurring de novo after the 20th week of gestation, remains the leading cause of maternal and fetal morbidity and mortality worldwide. Endothelial dysfunction is proposed to be a central feature of the pathophysiology of preeclampsia. However, the mechanism by which this endothelial dysfunction occurs remains uncertain. We investigated the predictive and diagnostic value of serum soluble vascular endothelial growth factor receptor-1 (VEGFR-1) with by comparison of its prepartum and postpartum serum levels in the management of women with PE. This prospective case-controlled study was composed of pre-eclamptic (n=44) and normal, healthy pregnant (n=44) women. Blood samples were collected before any intervention at the first antenatal examination of the women in the control group and at the admission of the women to the hospital in the PE group, additionally, from all women in the study groups within six hours of the postpartum period, and used for the serum VEGFR-1 analyses. Within both groups, prepartum serum levels of sVEGFR-1 were higher than postpartum levels (p<0.05). In PE, pre-partum and postpartum serum levels of sVEGFR-1 were higher than levels in the control group (p<0.05). Serum sVEGFR-1 levels of preeclamptic women were positively correlated with the degree of proteinuria (p<0.05, r=0.25), systolic (p<0.05, r=0.25), and diastolic blood pressure (p<0.05, r=0.31). These findings seem to point to an involvement of sVEGFR-1 in the pathophysiology of PE. Serum sVEGFR-1 has the potential to be used as a valuable biomarker in the prediction, diagnosis, and risk management of women with subtypes of PE including mild and severe PE, HELLP syndrome, and eclampsia. There is a need to study serum sVEGFR-1 as a biomarker in pregnant women with different subtypes of PE.

Frequency of Vitamin D Deficiency in Pre-Eclamptic Women

Aim: To determine the frequency of vitamin D deficiency in pre-eclamptic women admit in tertiary care hospital of Sindh Pakistan. Study design: Cross sectional study. Place and duration of study: Department of Obstetrics &amp; Gynaecology, Liaquat University of Medical &amp; Health Sciences Hospital Hyderabad from 1st December 2020 to 30th May 2021 Methodology: One hundred and fifty seven women with pre-eclampsia after 20 weeks of gestation were included. Detailed medical and obstetrical history and physical examination was carried out. Urine sample (MSU) was sent for test of proteinuria and after the confirm diagnosis of pre-eclampsia, blood sample was taken and sent to laboratory for measurement of serum Vitamin D (25(OH) D) levels and patients was categorized as Vitamin D deficient (below 75nmol/L (or 30ng/ml) of serum/plasma 25(OH)D concentration) or sufficient on the basis of serum vitamin D levels. Results: The average age was 29.06±3.96 years. Frequency of vitamin D deficiency was found in 130(82.8%) patients while sufficiency was found in 27(17.2%) of pre-eclamptic women. Conclusion: Pre-eclamptic women had a higher frequency of vitamin D deficiency. It is suggested that pregnant women at risk of vitamin D deficiency can be protected from hypertensive disease during pregnancy by a simple step of vitamin D supplementation during pregnancy. Keywords: Hypertensive disorders, Vitamin D deficiency, Pre-eclamptic

Maternal Blood Trace Element Levels in Preeclampsia: Comprehensive Systematic Review and Meta-Analysis

Introduction: Deficit in trace elements was frequent in pregnant women and could lead to preeclampsia development. This meta-analysis aimed to determine calcium, magnesium, zinc, iron, and copper serum levels in preeclampsia women compared to healthy pregnant women. Methods: A systematic search is conducted in PubMed, ScienceDirect, and Google Scholar from inception into March 25th, 2022 using keywords of “("calcium" OR "magnesium" OR "zinc" OR "copper" OR "iron" OR "trace element" OR "trace elements") AND ("serum" OR "blood") AND ("preeclampsia")”. Articles obtained from PubMed, ScienceDirect, and Google Scholar were 62, 31, and 119 respectively. The article screening process was based on the PRISMA 2020 guidelines. Study quality was assessed using NOS. Results: Fifty-four studies were included in this systematic review. Pooled analysis revealed that serum calcium (SMD = (-1.66; 95% CI = -2.05 to -1.28, magnesium (SMD = -1.28; 95% CI = -1.37 to -1.20, and zinc were significantly lower in preeclampsia (SMD = -2.4; 95% CI = -4.11 to -0.7. Serum iron was higher in preeclampsia (SMD = 1.71; 95% CI = 0.21 to 3.21). No significant different difference in serum copper level. Conclusion: The mean blood levels of calcium, magnesium, and zinc were considerably lower, while blood iron levels were higher in preeclamptic women compared to the healthy pregnant group. Copper levels were not significantly different between the two groups.

Circulatory Maternal Endothelin 1 and Matrix Metalloproteinase-9 Gene Expression in PREECLAMPSIA: A Study in Western Uttar Pradesh, India.

Preeclampsia (PE) is a multiorgan disease of pregnant women. The main pathophysiology of PE is a trophoblastic invasion into maternal circulation leading to alterations in circulatory levels of matrix metalloproteinases (MMPs), inflammatory markers, and endothelin 1(ET1) levels. Therefore, the present study has explored the role of MMP-9 and ET1 and their association in PE. The advantage of the study is to provide insight into the pathology of PE. These markers may help in the early diagnosis and prognosis of PE. To investigate MMP-9 gene expression, ET1 level in PE cases and their correlation with blood pressure (BP), gestational age, weight, and height. The study design was a case-control observational study, which included 70 subjects in each case (PE) and controls (normal pregnant women (NPW)). Whole blood (250 ul) was utilized for RNA extraction (Trizol method) and synthesized cDNA as per manufacturer protocol. MMP-9 gene expression was analyzed by real-time PCR. Serum was utilized for ET1 estimation by sandwich ELISA. The ET1 levels and MMP-9 gene expression were significantly increased in preeclamptic women as compared to controls. There was no significant correlation between MMP-9 gene expression and serum ET1 levels. However, a significant moderate association between systolic BP and diastolic BP with ET1 levels and MMP9 gene expression was seen in both PE and NPW. A significantly increased circulatory concentration of ET1 and MMP-9 gene expression in PE might be used as an early diagnostic as well as a prognostic marker of PE.

Effect of Progressive Muscle Relaxation Technique on Maternofetal Physiological Parameters and Stress among Preeclamptic Women

Effect of Progressive Muscle Relaxation Technique on Maternofetal Physiological Parameters and Stress among Preeclamptic Women

Critical Hypermagnesemia in Preeclamptic Women Undera MagnesiumSulfate Regimen: Incidence and Associated Risk Factors.

Magnesium sulfate is used as prophylaxis and treatment of severe preeclampsia/eclampsia, albeit its safety and toxicity are a concern. We designed this study to estimate the incidence of critical hypermagnesemia in severely preeclamptic women undera magnesiumsulfate regimen at 8h following its administration and to identify the associated risk factors as the primary outcomes. Also, secondary outcomes were to compare baseline characteristics, laboratory findings, and maternal-neonatal complications stratified by the baseline serum magnesium (Mg2+) in those women, and to assess the degree of agreement between patellar reflex and serum Mg2+ concentration 8h following magnesiumsulfate administration. We conducted a retrospective study including severely preeclamptic women receiving magnesium sulfate from June 2016 to May 2021. We enrolled 429 women in the study. Two-hundred sixty-one (60.8%) of the included women developed critical hypermagnesemia. Preeclamptic women with high baseline serum Mg2+ concentration demonstrated significantly affected renal functions, hepatic transaminase activities, and low platelet count as well as more reported maternal complications compared to those with low baseline serum Mg2. Multivariable logistic regression revealed that a lower gestational age, a higher uric acid concentration, and a higher baseline serum Mg2+ concentration were independently associated with an increased risk of critical hypermagnesemia. The agreement between deep tendon reflex assessment and serum Mg2+ concentration was slight although not significant. The maternal-neonatal outcomes were non-significant in women with critical hypermagnesemia. More vigilant monitoring through assessment of both serum Mg2+ concentration and deep tendon reflex should be considered especially in high-risk women.

25-Hydroxy Vitamin D Level and Its Correlation with Mean Platelet Volume in Preeclampsia.

Preeclampsia is one of the challenging complications of pregnancy, of which little is known about its etiology and pathogenesis. Many studies have shown higher mean platelet volume (MPV) in preeclamptic patients. Vitamin D deficiency is in association with larger-size platelets. Thus, we aimed to determine the correlation of vitamin D with MPV in preeclamptic patients. This prospective case-control study was conducted in two tertiary hospitals in Tehran, Iran. Overall, 85 preeclamptic pregnant women and 85 normotensive pregnant women were entered between 2017 and 2018. Serum vitamin D concentration (ng/ml) and MPV (femtoliter) were measured for all patients. MPV was significantly higher in the cases compared to controls (10.59±1.08 vs 8.10±0.95, P=0.0001). In addition, serum vitamin D level in the preeclamptic group was significantly lower in compare to the control group (17.79±11.03 vs 30.24±12.49; P=0.0001). In multivariate logistic regression analysis, high age of mother (OR: 1.13; 95% CI: 1.01-1.27; P=0.03), low level of serum vitamin D (OR: 0.93; 95% CI: 0.87-0.99; P=0.02) and high MPV (OR: 8.83; 95% CI: 4.17-18.67; P=0.0001) were independent predictors of preeclampsia. Moreover, a correlation analysis revealed that vitamin D levels correlated negatively with MPV (r= -0.41, P<0.0001). Low levels of vitamin D in preeclamptic pregnancy are associated with higher platelet activity and thrombosis. In fact, the increment of MPV level might be a potential pathway for adverse outcomes of pregnancy including preeclampsia in the context of vitamin D deficiency.

Red-Complex Bacterial Levels in Pregnant Women With Preeclampsia and Chronic Periodontitis

The presence of red-complex bacteria (RCB) has been associated with the occurrence of not only periodontal disease but also other systemic diseases, thereby potentiating an oral-systemic relationship. This study aimed to explore the levels of periodontal RCB in pregnant preeclamptic women with periodontal disease, potentiating the pathophysiology of a bacterial association in both periodontitis and preeclampsia. Six hundred pregnant women (aged 20 to 35 years) in their third trimester were selected and divided into 3 groups comprising a control group (systemically and periodontally healthy pregnant women), group A (preeclamptic women with chronic periodontitis), and group B (preeclamptic women without chronic periodontitis). Demographic variables and periodontal parameters were recorded. Other variables such as systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the urine protein content were also estimated. RCB, namely Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tenerella forsythia (Tf), were assessed in both subgingival plaque samples and placental samples of all the pregnant participants in the study. The mean weight, mean body mass index, mean SBP, mean DBP, and mean urine protein content were significantly elevated in group A and group B when compared to the control group. Preeclamptic women with chronic periodontitis (group A) had higher levels of plaque index, probing pocket depth, bleeding on probing, and clinical attachment level as compared with the other groups. The numbers of the RCB were found to be elevated in group A, out of which Pg was found to be more prevalent. Our findings indicate that the periodontal indices, blood pressure, and urine protein content were found to be higher in preeclamptic women with periodontitis. Hence, reducing the periodontal bacterial load in pregnant women via good oral hygiene maintenance would further reduce the putative risk of adverse pregnancy outcomes including preeclampsia in these women.

Reliability of Rodent and Rabbit Models in Preeclampsia Research.

In vivo studies on the pathology of gestation, including preeclampsia, often use small mammals such as rabbits or rodents, i.e., mice, rats, hamsters, and guinea pigs. The key advantage of these animals is their short reproductive cycle; in addition, similar to humans, they also develop a haemochorial placenta and present a similar transformation of maternal spiral arteries. Interestingly, pregnant dams also demonstrate a similar reaction to inflammatory factors and placentally derived antiangiogenic factors, i.e., soluble fms-like tyrosine kinase 1 (sFlt-1) or soluble endoglin-1 (sEng), as preeclamptic women: all animals present an increase in blood pressure and usually proteinuria. These constitute the classical duet that allows for the recognition of preeclampsia. However, the time of initiation of maternal vessel remodelling and the depth of trophoblast invasion differs between rabbits, rodents, and humans. Unfortunately, at present, no known animal replicates a human pregnancy exactly, and hence, the use of rabbit and rodent models is restricted to the investigation of individual aspects of human gestation only. This article compares the process of placentation in rodents, rabbits, and humans, which should be considered when planning experiments on preeclampsia; these aspects might determine the success, or failure, of the study. The report also reviews the rodent and rabbit models used to investigate certain aspects of the pathomechanism of human preeclampsia, especially those related to incorrect trophoblast invasion, placental hypoxia, inflammation, or maternal endothelial dysfunction.

Association of vitamin D deficiency and vitamin D receptor (VDR) gene single-nucleotide polymorphism (rs7975232) with risk of preeclampsia

Background Preeclampsia has a multifactorial-yet-elusive etiology. Recent reports suggest a link between preeclampsia and vitamin D (VD) metabolic axis. Genetic variations like single-nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) gene can alter the metabolic role of VD, which have been shown by several genetic association studies. However, there is discordance among these studies. Objective The current study aimed to investigate the association of VDR gene polymorphism (ApaI) and VD deficiency with risk of developing preeclampsia. Patients and Method In this case–control study, 40 preeclamptic and 40 normotensive pregnant women were compared for VD status and VDR gene polymorphism. Serum 25-hydroxyvitamin-D [25(OH) D] level was determined by enzyme-linked immunosorbent assay (ELISA) and VDR gene polymorphism Apa1 was analyzed by Allele specific polymerase chain reaction (AS-PCR) using sequence specific primers. Results Serum levels of 25(OH) D were very low but comparable in both preeclamptic and normotensive pregnant women. The difference between the two groups were not statistically significant (p = .423). VDR gene polymorphism ApaI (rs7975232) was found not to have significant association with the risk of developing preeclampsia. The frequencies of wild genotype (GG) in preeclamptic and normotensive women were 27.5% and 22.5% respectively. A total of 25% of preeclamptic women had mutant homozygous genotype (TT) and 17.5% of normotensive women had mutant homozygous genotype. The frequency of mutant heterozygous genotype (GT) in preeclamptic patients was 47.5% and in normotensive women was 60%. The variation of wild and mutant genotypes between the two groups was not statistically significant (p > .05). Conclusion This study showed that VDR gene polymorphism (ApaI) and VD deficiency are not associated with the risk of preeclampsia.

Role and estimation of serum calcium, serum uric acid and C-RP in preeclamptic and normal pregnant women in Dhiraj General Hospital of Sumandeep Vidyapeeth Vadodara

Preeclampsia is one of the major conditions causing maternal morbidity and mortality throughout the world. Hyperuricemia due to oxidative stress is known to be associated with deleterious effects on endothelial function, oxidative metabolism, platelet adhesiveness and aggregation. C-reactive protein (CRP) is an acute phase reactant protein, plays a role in eliciting the inflammatory response characteristic of preeclampsia. Patients with Preeclampsia showed the low levels of serum calcium. To estimate serum uric acid, CRP and serum calcium in cases and controls and to study the association of the levels of serum uric acid, CRP and calcium with preeclampsia. A case control study conducted on 100 patients with clinically diagnosed preeclampsia and 100 normotensive singleton pregnant women as controls from the general population from Dhiraj General Hospital, Piparia, Vadodara, Gujarat. 6 ml of each venous blood was collected to estimate the Serum Uric Acid, CRP and Serum Calcium levels in subject. The data was analyzed and expressed in terms of mean ± SD. There was statistically significant increase in the levels of serum uric acid, CRP (P &lt; 0.001) and statistically decreased levels of serum calcium (P &lt; 0.001) in cases as compared to the normal controls.

Aspirin Inhibits the Inflammatory Response of Protease-Activated Receptor 1 in Pregnancy Neutrophils: Implications for Treating Women with Preeclampsia.

Neutrophils expressing cyclooxygenase-2 (COX-2) extensively infiltrate maternal blood vessels in preeclampsia, associated with vascular inflammation. Because pregnancy neutrophils also express protease-activated receptor 1 (PAR-1, F2R thrombin receptor), which they do not in non-pregnant subjects, they can be activated by proteases. We tested the hypothesis that aspirin at a dose sufficient to inhibit COX-2 would reduce inflammatory responses in preeclampsia neutrophils. Neutrophils were isolated from normal pregnant and preeclamptic women at approximately 30 weeks' gestation. Normal pregnancy neutrophils were treated with elastase, a protease elevated in preeclampsia, or elastase plus aspirin to inhibit COX-2, or elastase plus pinane thromboxane, a biologically active structural analog of thromboxane and a thromboxane synthase inhibitor. Preeclamptic pregnancy neutrophils were treated with the same doses of aspirin or pinane thromboxane. Confocal microscopy with immunofluorescence staining was used to determine the cellular localization of the p65 subunit of nuclear factor-kappa B (NF-κB) and media concentrations of thromboxane were measured to evaluate the inflammatory response. In untreated neutrophils of normal pregnant women, p65 was localized to the cytosol. Upon stimulation with elastase, p65 translocated from the cytosol to the nucleus coincident with increased thromboxane production. When neutrophils were co-treated with aspirin or pinane thromboxane, elastase was not able to cause nuclear translocation of p65 or increase thromboxane. In untreated neutrophils of preeclamptic women, the p65 subunit was present in the nucleus and thromboxane production was elevated, but when preeclamptic neutrophils were treated with aspirin or pinane thromboxane, p65 was cleared from the nucleus and returned to the cytosol along with decreased thromboxane production. These findings suggest that COX-2 is a downstream mediator of PAR-1 and demonstrate that PAR-1- mediated inflammation can be inhibited by aspirin. Given the extensive and ubiquitous expression of PAR-1 and COX-2 in preeclamptic women, consideration should be given to treating women with preeclampsia using a dose of aspirin sufficient to inhibit COX-2.

Platelet Count in Women with Pregnancy Induced Hypertension

Objective: One of the most common and potential life threatening complications of pregnancy is pregnancy induced hypertension. This crosssectional study aimed to investigate the relationship between platelet count and pregnancy induced hypertension. Materials and Methods: This is a present crosssectional study was carried out in the Department of Medicine and Obstetrics and Gynecology, Maheshwara Medical College &amp; Hospital over a period of 1 year among 60 subjects. The subjects for this cross-sectional study included consecutively - recruited Normotensive (n = 130) serve as a control, Non-Sever Pre-eclamptic (N = 35) and Severe pre-eclamptic (n = 35). All consenting, adult (≥ 18 years) pregnant women who were confirmed to have pregnancy induced hypertension by an Obstetrician constituted the subjects for these subjects. Results: A total of 200 pregnant women were included in the study. Platelet count and platelet crit levels tend to decrease as pre-eclampsia becomes more severe. In this study, no statistically significant differences were observed between the three groups in age, residence, number of pregnancies (gravidity), number of deliveries (parity), gestational age, and BMI, but there was a significant difference between the three studied groups with regards to SBP, DBP and MAP which increased with severity of preeclampsia (P&lt;0.001). The value of PLT accounts 180(97–352) ×103/μl for pre-eclamptic women and 260(139–445) ×103/μl for normotensive pregnant women (p&lt;0.001). Conclusion: Platelet indices, including platelet count, mean platelet volume, platelet distribution width, and Platelet crit, havebeen identified as promising candidate markers for predicting preeclampsia in pregnant women. In the future, a serial examination of these indicators during several trimesters of pregnancy should be conducted.

Perinatal Outcome and Its Association with Blood Pressure Levels in Women with Preeclampsia.

Timing and mode of delivery in women with preeclampsia remains challenging, often balancing the risk of severe maternal complications and preterm delivery with its risks for the newborn. It is known that women with very high blood pressure levels in pregnancy have more unfavourable outcomes, but there is little data on neonatal outcome in these cases and the effect of the delivery mode. We included 158 preeclamptic women in our single-centre retrospective cohort study. Patients were divided into three subgroups depending on blood pressure levels, and delivery mode as well as neonatal outcomes were analysed. Furthermore, the effect of gestational age at delivery was assessed. Maternal blood pressure levels correlated negatively with gestational age at delivery (p = 0.007) and positively with delivery via caesarean section (p = 0.003). Induction of labour was more frequent in women with lower blood pressure levels (p = 0.008) and higher gestational age (p &lt; 0.001). If labour was induced, vaginal delivery was achieved equally often in all gestational ages. Neonatal outcome appears to be more favourable after vaginal delivery compared to planned caesarean section (p &lt; 0.001). Induction of labour should be discussed generously in preeclamptic women, even if blood pressure levels are high and/or gestational age is young, as success rates seem to be adequate and neonatal outcome is more favourable after vaginal delivery. Large prospective trials are needed to better evaluate success rates, risks and complications of induced labour and the effects of delivery mode on neonatal outcome in preeclampsia.

Increased Intima-Media Thickness of Carotid and Femoral Arteries in Women with Early Preeclampsia

Background: Preeclampsia can increase the risk of cardiovascular diseases (CVDs) later in life. Also, increased intima-media thickness (IMT) of the carotid artery was introduced as an independent risk factor for CVDs. Objectives: This study aimed to evaluate and compare the IMT of carotid and femoral arteries between women with early preeclampsia and normotensive pregnant and nulligravid women. Methods: In this study, which was conducted between May 2019 and January 2020, three groups of women were evaluated: early-onset preeclamptic pregnant women, normotensive pregnant women, and nulligravid women. The IMTs of the common femoral artery, superficial femoral artery, common carotid artery, carotid bulb, and internal carotid artery were measured using B-mode ultrasound. Results: A total of 100 women were enrolled in each group. The means ± SD of age in preeclamptic, normotensive and nulligravid women were 27.78 ± 3.23, 27.16 ± 3.09, and 27.11 ± 2.95, respectively. The mean gestational age of the two pregnant groups was nearly 32 weeks. Based on the results, the mean systolic blood pressure, diastolic blood pressure, and arterial pressure were significantly higher in the preeclamptic group compared to the other groups (P &lt; 0.001). The mean IMT of both sides of the common carotid artery, carotid bulb, internal carotid artery, common femoral artery, and superficial femoral artery was significantly higher in the preeclamptic group compared to normotensive pregnant and nulligravid women (P &lt; 0.001). Conclusion: Preeclampsia was associated with the increased IMT of common and internal carotid arteries, as well as common and superficial femoral arteries. Therefore, IMT measurements in preeclamptic women can provide an opportunity to identify those who may benefit from early screening and preventive care to reduce the risk of CVDs in the future.

Evaluation of Urinary Calcium–Creatinine Ratio for Early Prediction of Preeclampsia

Background: Preeclampsia (PE) is one of the most important hypertensive disorders in pregnancy. It is one of the fatal complications with significant mortality and morbidity. Incidence of preeclampsia is around 5-10% of all pregnancies, and in developing countries like Bangladesh it is around 4-18%. Objective: The objective of this study was to determine the efficacy of urinary calcium-creatinine ratio in a spot urine sample for early prediction of preeclampsia in pregnant women. Methods: It's a cross sectional type of analytical study, done in the department of Obstetrics &amp; Gynaecology, Sir Salimuilah Medical College Mitford Hospital, Dhaka. After fulfilling inclusion and exclusion criteria total 100 pregnant women with risk factors of preeclampsia were enrolled as the study population. Results: Among different parameters serum calcium concentration of normal pregnancy and preeclampsia group varied significantly (p&lt;0.05). Women with preeclampsia showed reduced excretion of calcium in comparison to normal pregnant women when spot urinary calcium concentration was evaluated. In this study comparison of spot urinary calcium-creatinine ratio in normal pregnant woman and in preeclamptic women was done and the result was highly significant (p &lt;0.001). Conclusion: This study is intended to identify at risk patients and put selection criteria for primary prevention to reduce morbidity and mortality in patients of preeclampsia. It showed lower urinary calcium excretion and calcium-creatinine ratio in preeclamptic women than normotensive pregnant women. Therefore, a single random urinary calcium-creatinine may be an effective tool for the early diagnosis of preeclampsia.

Prediction model for hypertension after preeclampsia in initially normotensive women; the Queen of Hearts cohort

Abstract Background Timely detection and treatment of hypertension prevents cardiovascular diseases. Formerly preeclamptic women are at increased risk for hypertension, but targeted and structural follow-up of these women is lacking. Purpose To develop a prediction model for the development of hypertension in the decade following preeclampsia in women who were initially normotensive shortly after pregnancy. Methods In this longitudinal cohort study, formerly preeclamptic women were invited twice for a cardiovascular assessment. The first visit took place at a median interval of 10 months after delivery and a second visit 10 years later as part of the Queen of Hearts cohort study on early detection of heart failure among young women with a history of preeclampsia (ClinicalTrials.gov Identifier NCT02347540). Normotensive women at the first visit were divided in two groups whether or not they had developed hypertension during visit 2. Hypertension was defined as SBP ≥130 mmHg and/or DBP ≥80 mmhg and/or use of antihypertensive medication. We developed a prediction model using multivariable logistic regression analysis. The model was internally validated with bootstrapping techniques. Results Of the 259 women, 185 (71%) were normotensive at first visit of which 49 (26%) had developed hypertension at the second visit. The prediction model, based on birth weight centile, mean arterial pressure, total cholesterol, left ventricular mass index and left ventricular ejection fraction, had a good to excellent discriminative ability of AUC-ROC-curve 0.82 (95% CI 0.75–0.89) with an optimism corrected AUC of 0.80. Sensitivity and specificity of our model to predict yearly 10% risk to develop hypertension was 98% and 65% respectively and positive- and negative-predictive values were 50% and 99% respectively. Conclusions Based on five easily available variables, we developed a good-to-excellent performing predictive tool to identify incident hypertension following preeclampsia in women that were normotensive shortly after pregnancy. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was partially supported by funding of de Nederlandse Hartstichting (Dutch Heart Foundation, grant number: 2013T084, Queen of Hearts study)

Female-specific reference values for blood pressure and its relationship with subclinical echocardiographic findings in women with a history of preeclampsia: the Queen of Hearts study

Abstract Introduction Hypertension is the most crucial modifiable risk factor for cardiovascular disease (CVD). Sex differences in what is considered optimal blood pressure (BP) might deviate from current sex-blinded guidelines for hypertension. In women, an obstetric history of preeclampsia relates to postpartum hypertension and substantially increases the risk of premature CVD. Purpose To establish female-specific reference values for BP in relatively young women and assess its association with subclinical aberrant echocardiographic findings in a high-risk female population. Methods Data was used from the Queen of Hearts study; a cross-sectional cohort study on early detection of heart failure among young women with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancy. The control group was used to non-parametrically establish reference values for BP (95th percentile). The association between the derived reference values and the risk of subclinical aberrant echocardiographic findings was evaluated in the former preeclamptic group using logistic regression. All women were admitted to a standardized cardiovascular assessment including transthoracic echocardiography and 30-minutes BP measurement. Subclinical echocardiographic findings included left ventricular (LV) hypertrophy (LVH), LV concentric remodelling (LCVR), diastolic dysfunction (DD) and impaired LV ejection fraction (LVEF, &amp;lt;55%). Results A total of 429 women in the healthy control group and 856 in the former preeclamptic group were included (44±8 and 38±8 years, respectively). In the healthy control group, 97.7% and 99.8% of women had a systolic (SBP) and diastolic BP (DBP) value below the European Society of Cardiology (ESC) guidelines for hypertension. Overall, the derived reference value for SBP and DBP in our control group was 133 and 82 mmHg, respectively. Age-specific reference curves are presented in Figure 1 and 2. In the subgroup of former preeclamptic women 10.4% and 14.6% had SBP and DBP levels above 133 mmHg and 82mmHg, respectively. In this group, the Odds Ratio (OR) for subclinical aberrant echocardiographic findings when having SBP ≥133mmHg was 5.3 (95% CI 2.3–12.3) for LVH, 1.4 (95% CI 0.6–3.2) for LVCR, 5.9 (95% CI 3.3–10.7) for DD and 1.3 (95% CI 0.3–6.0) for impaired LVEF. For DBP ≥82mmHg, the OR for LVH was 3.5 (95% CI 1.5–8.0), LVCR 1.3 (95% CI 0.6–2.7), DD 3.4 (95% CI 1.9–6.0) and impaired LVEF 1.5 (95% CI 0.4–5.3). Conclusions Upper limits for SBP and DBP values in current guidelines correspond with the value of less than 2% of women in our healthy (no pre-eclampsia) population. We derived new reference values with the upper limit corresponding with the upper 5th centile. Values above this level, even below decision limits for hypertension, are associated with abnormal subclinical cardiac function and geometry in a high-risk young female population. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation

Arterial health abnormalities in women with pre-eclampsia: contributing role of central obesity

Abstract Introduction Women who suffer from pre-eclampsia (PE) are at higher risk of developing cardiovascular disease (CVD) later in life. This risk can be explained in part by the observation of worse arterial health in these women, with PE either acting as a cause or harbinger of a worse baseline risk profile. Central obesity (CO) is an established risk factor for PE, while it also adversely affects cardiovascular risk. However, whether CO contributes to further worsening of arterial hemodynamics in pre-eclamptic women remains unclear. Purpose To evaluate the effect of CO combined with previous PE on women's arterial hemodynamics. Methods We studied 40 women with history of PE &amp;lt;6 years and 40 age-matched women with previous normotensive pregnancy (controls) in the same timeframe. We estimated aortic stiffness, central blood pressure, and measures of steady and pulsatile arterial load with validated techniques combining applanation tonometry and transthoracic echocardiography. CO was defined as a waist-to-hip ratio (WHR) ≥0.85 according to WHO criteria for women. Differences in arterial hemodynamics across the 3 groups [PE with CO (PE-CO), PE without CO (PE-noCO), controls] were assessed with One-Way ANOVA, and in multivariable linear regression models adjusted for age, hypertension, diabetes, serum creatinine, and parity. Results Twenty-six (65%) of the PE women had CO, compared to 18 (45%) of controls (p=0.07). Patient characteristics are described in the Table. In unadjusted analyses, PE-CO women had higher central systolic blood pressure as compared to PE-noCO and controls respectively (117±21 vs 100±12 and 95±9 mmHg, p&amp;lt;0.01), as well as higher carotid-femoral pulse wave velocity (6.58±0.97 vs 5.95±1.01 and 5.68±0.75 m/s, p&amp;lt;0.01) and forward pressure wave amplitude (42.32±11.16 vs 33.31±6.85 and 37.12±8.70 mmHg, p=0.01), with lower proximal aortic compliance (8.56±3.19 vs 11.47±0.95 and 11.06±3.59x10–6 cm4/dyne, p=0.01) and total arterial compliance (1.38±0.42 vs 1.74±0.53 and 1.71±0.45 mL/mmHg, p=0.01). (Figure) After adjustment for potential confounders in multivariable linear regression, PE-CO women had higher central systolic blood pressure (mean difference [MD] = 10±2.5 mmHg, p&amp;lt;0.01), carotid-femoral pulse wave velocity (MD = 0.42±0.15 m/s, p&amp;lt;0.01) and lower proximal aortic compliance (MD = −1.13±0.63x10–6 cm4/dyne, p=0.04) as compared to controls, while hemodynamics of PE-noCO did not significantly differ from controls. Conclusion We demonstrate for the first time the contribution of CO in adversely affecting arterial health and central hemodynamics in women with PE. Conversely, women with prior PE who did not have CO had similar arterial hemodynamics as compared to women with normotensive pregnancies. Understanding that worse arterial stiffness and hemodynamics are linked to future CVD, our results suggest that PE-CO may represent a higher risk subgroup who may be candidates for early, targeted efforts at primary prevention of CVD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Heart Team Grant from the University of Ottawa Heart Institute Foundation

THE ROLE OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH PREECLAMPSIA.

To investigate the changes in the microvascular structure of the retina and optic disk by comparing the optical coherence tomography angiography findings in preeclamptic patients with those in healthy pregnant women and healthy nonpregnant women and also to evaluate the preeclamptic patients after delivery by showing whether the changes are permanent or not. Fifty preeclamptic, 50 healthy pregnant, and 50 healthy nonpregnant women enrolled in three groups (preeclamptic pregnant women group, healthy pregnant women group, and nonpregnant women group; respectively). Patients in the preeclamptic pregnant women group were evaluated at three different time points including up to 3 hours before delivery (Group 1), 2, or 3 days after delivery (Group 2), and 6 weeks after delivery (Group 3), and compared with each other. All patients underwent a comprehensive ophthalmologic examination including optical coherence tomography angiography. Choriocapillaris blood flow area, deep foveal density, deep temporal density, deep nasal density, and radial peripapillary capillary inside disk density values were significantly lower in the preeclamptic pregnant women group than in the healthy pregnant women group. Deep foveal density and deep nasal density values were significantly higher in Group 3 than in Group 1 and 2, and deep temporal density was significantly higher in Group 3 than in Group 1. Optical coherence tomography angiography diagnosed decreased deep retinal capillary density values in the macula of patients with preeclampsia, but these results improved after delivery.