Normotensive Women Research Articles

The interval between the onset of increased blood pressure and proteinuria in preeclampsia and the contributing factors.

New-onset proteinuria, as a pivotal sign of representative renal lesions in preeclampsia, is still the most common diagnostic tool for this condition and has been proven to be related to a significantly abnormal sFlt-1/VEGF ratio in circulation. At the same time, blood pressure control plays a vital role in the occurrence and evolution of proteinuria. Therefore, it is particularly helpful to investigate their interval, not only for performing urinalysis for protein more accurately but also for evaluating blood pressure as well as the aggravation of illness, as the related research is limited. This retrospective study included 515 preeclampsia patients and 358 normotensive pregnant women who labored in the Second Hospital of Tianjin Medical University from January 2016 to January 2020. First, we described the onset circumstance of high blood pressure and proteinuria as well as the interval among the case group and the subgroups. Then, we determined whether there were significant differences in the basic information, laboratory test results, and newborns between the case and normal groups. Finally, multifactor ANOVA was used to determine the factors influencing the interval. 1. The two most common complications in preeclampsia were proteinuria (88.35%) and placental dysfunction (5.05%). Moreover, 72.04% of preeclampsia cases were diagnosed by abnormal blood pressure together with new-onset proteinuria. 2. The average interval between high blood pressure and proteinuria was 22 gestational days (from 0 to 106days), and this interval was not significantly different between mild and severe PE (26days vs. 21days, P > 0.05) but significantly differed between early-onset and late-onset PE (9days vs. 28days, P < 0.05). 3. The number of prenatal visits, serum creatinine in the early trimester, gestational time and diastolic blood pressure value when increased blood pressure was initially detected may influence the interval between the onset of increased blood pressure and proteinuria. New-onset proteinuria was still the main parameter for identifying preeclampsia. The interval between increased blood pressure and proteinuria was probably related to the imbalance in the sFlt-1/VEGF ratio; therefore, we should pay attention tomonitor proteinuria during the prenatal visits, especially for patients with a lower frequency of prenatal visits, higher serum creatinine in the early trimester, earlier onset and higher diastolic blood pressure at the initial onset of increased blood pressure.

Increased Expression of Neprilysin Is Associated with Inflammation in Preeclampsia

Preeclampsia (PE) is associated with a finely tuned equilibrium between trophoblast cell invasion and fetal-maternal immunological tolerance. An imbalance between proinflammatory (IL-6) and anti-inflammatory (IL-10) cytokines is a hallmark of PE. Neprilysin (NEP), a membrane-bound metalloprotease, is vulnerable to the inflammatory environment and plays a significant role in modulating vascular tone. The aim of this study was to determine the correlation between NEP (mRNA and protein) levels and the inflammatory status in PE patients compared to healthy pregnant women and to identify the role of NEP in evaluating the severity of preeclampsia. The study group comprised 52 pregnant women with PE while the control group comprised 47 normotensive pregnant women. After a caesarean section, placental tissue samples from patients and controls were collected to measure the expression levels of IL-6, TGF-β, IL-10, and NEP mRNA. In addition, an enzyme-linked immunosorbent assay was used to assess the quantity of NEP protein in blood samples. Our results revealed a significant positive correlation between NEP (mRNA and protein) and proinflammatory markers IL-6 and TGF-β levels in patients compared to controls and a significant inverse correlation between NEP and anti-inflammatory cytokine IL-10. Moreover, this is the first study to find a strong positive correlation between NEP level and PE severity. In conclusion, in PE patients, there is a substantial relationship between NEP, the degree of inflammation, and PE severity. NEP could act as a potential biomarker for diagnosis and prognosis of PE.

Perinatal outcomes in women with lower-range elevated blood pressure and stage 1 hypertension: insights from the Kaya health and demographic surveillance system, Burkina Faso

BackgroundThe impact of lower thresholds for elevated blood pressure (BP) on adverse perinatal outcomes has been poorly explored in sub-Saharan African populations. We aimed to explore the association between lower BP cutoffs (according to the 2017 American College of Cardiology/American Heart Association [ACC/AHA] criteria) and adverse perinatal outcomes in Kaya, Burkina Faso.MethodsThis retrospective cohort study included 2,232 women with singleton pregnancies between February and September 2021. BP was categorized according to the ACC/AHA criteria and applied throughout pregnancy. A multivariable Poisson regression model based on Generalized Estimating Equation with robust standard errors was used to evaluate the association between elevated BP, stage 1 hypertension, and adverse perinatal outcomes, controlling for maternal sociodemographic characteristics, parity, and the number of antenatal consultations, and the results were presented as adjusted risk ratios (aRRs) with corresponding 95% confidence intervals (CIs).ResultsOf the 2,232 women, 1000 (44.8%) were normotensive, 334 (14.9%) had elevated BP, 759 (34.0%) had stage 1 hypertension, and 139 (6.2%) had stage 2 hypertension. There was no significant association between elevated BP and adverse pregnancy outcomes. Compared to normotensive women, women with elevated BP had a 2.05-fold increased risk of delivery via caesarean section (aRR;2.05, 95%CI; 1.08–3.92), while those with stage 1 hypertension had a 1.41-fold increased risk of having low birth weight babies (aRR; 1.41, 95%CI; 1.06–1.86), and a 1.32-fold increased risk of having any maternal or neonatal adverse outcome (aRR; 1.32, 95%CI; 1.02–1.69).ConclusionsOur results suggest that the risk of adverse pregnancy outcomes is not increased with elevated BP. Proactive identification of pregnant women with stage 1 hypertension in Burkina Faso can improve hypertension management through enhanced clinical surveillance.

The gut microbiota composition and metabolites are different in women with hypertensive disorders of pregnancy and normotension: A pilot study.

Hypertensive disorders of pregnancy (HDP) are one of the main causes of perinatal morbidity. Gut microbiota influences host inflammatory pathways, glucose, and lipid metabolism. However, there is a lack of studies available on gut microbiota in HDP. We investigate the mechanistic and pathogenic role of microbiota in the development of HDP, and want to treat HDP with gut microbiota. We performed a case-control study to compare fecal samples of HDP and normotensive pregnant women by 16S ribosomal RNA sequencing. Fecal samples, collected from pregnant women, were divided into groups P and C (pregnant women with HDP and normotension, respectively). There were six pregnant women in group P and nine pregnant women in group C. Age of pregnant women is from 18 to 40 years and gestational age is from 27 to 40 weeks. DNA was extracted from fecal samples; a gene library was constructed and analyzed using bioinformatics. Finally, we determined the changes in the microbiome by alpha diversity, beta diversity, classification abundance, and taxonomic composition analyses. Escherichia (10.48% in group P and 0.61% in group C) was the dominant bacterium in HDP patients by classification abundance analysis, which can lead to the development of preeclampsia through inflammatory response. We found that pregnant women with HDP had higher abundance of Rothia (p = 0.04984), Actinomyces (p = 0.02040), and Enterococcus (p = 0.04974) and lower abundance of Coprococcus (p = 0.04955) than pregnant women with normotension for the first time by taxonomic composition analysis. Based on the Kyoto Encyclopedia of Genes and Genomes database analysis, physiological and biochemical functions of HDP patients were significantly weakened, especially in energy metabolism. We found the effect of changes in gut microbiota on the development of HDP. In comparison with group C, group P contained more harmful bacteria and less beneficial bacteria, which are associated with HDP. Our research further provides a basis for a clinical application for HDP treatment using antibiotics and probiotic supplementation.

The Association Of Adiponectin, Homocysteine, B 12 And Folic Acid In Iraqi Women With Preeclampsia And Its Severity

Background: preeclampsia is a common obstetric disorder that remains a leading cause of maternal and perinatal mortality and morbidity. Maternal serum concentrations of adiponectin, folate, homocysteine, and vitamin B12 have been found to be associated with pre-eclampsia. Nevertheless, reported studies involved still not clear with variable reliably. The aim of the present study is to examine the relationship between these biomarkers and pre-eclampsia and its severity in Iraqi population. Aims: The study aims to evaluate the association between maternal serum adiponectin, homocysteine, B12 and Folic acid and preeclampsia and its severity. Study design and setting: A case control study carried out in Al-Zahraa Maternity and Pediatric Teaching Hospital in Najaf city/ Iraq from the 1st of December 2019 to the 1st of December 2020. Patient and Methods: The study included 50 pregnant women with preeclampsia and a comparative control group of 50 normotensive pregnant women. Preeclamptic women were further subdivided into 14 women with severe preeclampsia and 36 women with mild preeclampsia. Serum Adiponectin, Homocysteine, B 12, and Folic acid were measured by using special ELIZA (Enzyme linked immunosorbent assay) technique. Results: There was a significant increment in the level of Adiponectin and Homocysteine while vitamin B12 and Folic acid were significantly decreased in preeclamptic pregnant women in comparison to the control group. On the other hand, there was no significant relation between the severity of preeclampsia and the level of Adiponectin, Homocysteine, Vitamin B 12, and Folic acid. Conclusion: Women with preeclampsia had significantly lower vitamin B12 and folic acid and significantly higher concentrations of adiponectin and homocysteine than normotensive pregnant women, but no relation with its severity.

The Risk of Persistent Hypertension and Chronic Kidney Disease in Early- and Late-Onset Preeclampsia: A Report From Developing Country.

Preeclampsia (PE) has been disproportionately prevalent in developing countries and constitutes a leading cause of maternal mortality, and also has long-term impacts, including renal consequences.This study aimed to explore the risk of persistent hypertension and kidney failure in early-onset PE (EOP) and late-onset PE (LOP) in the five years after delivery. This retrospective cohort study included women with a prior history of severe PEor normotensive pregnancy admitted to tertiary hospitals in Indonesia. The blood pressure, body mass index (BMI), urea, creatinine serum, and protein urine were analyzed, and the risk of chronic kidney disease (CKD) after five years was performed using theKidney Disease Improvement Global Outcomes (KDIGO) classification. Twenty-seven EOP, 35 LOP, and 30 normotensive cases were included. Mean blood pressure after five years was recorded as 115.6 ± 14.25 mmHg in the normotensive group, 131.82 ± 19.34 mmHg in the LOP group, and 154.96 ± 23.48 mmHg in the EOP group. According to the KDIGO classification, the normotensive group had an average 10% risk of CKD, but severe PE had a risk of CKD greater than 90%. In the severe PE group, the risk of CKD was 20.94 times higher compared to normotensive women (OR 20.94; 95% CI 2.67-163.72, p = 0.004). The risk of CKD in the EOP group was 6.75 times higher than in the LOP group (OR 6.75; 95% CI 2.19-20.76, p = 0.001), whereas persistent hypertension in the EOP group was 5.78 times higher than in the LOP group (OR 5.78; 95% CI 1.91-17.395, p = 0.002). PE women have a higher risk of CKD than normotensive women. Women with a history of EOP are more likely to develop persistent hypertension and CKD than women with a prior LOP history.

Angiogenic growth factors, oxidative stress and haematobiochemical measures as predictors of preeclampsia with and without foetal growth restriction: A case-control study in a Ghanaian population

IntroductionThis study compares the angiogenic growth mediators (AGMs), oxidative stress (OS) and haematobiochemical profile as well as foeto-maternal outcomes of preeclampsia (PE) with and without foetal growth restriction (FGR) and the discriminative potential of these markers for identifying these conditions. MethodsThis hospital-based case-control study recruited a total of 209 women including 109 PE women without FGR and 48 PE women with FGR as cases whereas 52 normotensive pregnant women were recruited as controls. OS and AGMs and haematobiochemical markers were measured for all participants. ResultsThe rates of foetal complications including intrauterine foetal death and foetal distress were more common in PE with FGR than PE without FGR (p < 0.05) but maternal complications were comparable across these groups (p > 0.05). Of the haematobiochemical markers, placental growth factors (PIGF), PIGF/8-Isoprostane, sFlt-1/PIGF (AUC = 0.87, p < 0.001), soluble FMS-tyrosine kinase receptor-1 (sFlt-1) (AUC = 0.85, p < 0.001), total antioxidant capacity, 8-isoprostane (AUC = 0.83, p < 0.001) and lactate dehydrogenase (AUC = 0.70, p < 0.001) were more associated and showed at least an acceptable discrimination for PE with FGR against PE only. DiscussionThe occurrence of FGR in PE patients does not necessarily indicate a severe maternal presentation of the condition but a tendency for adverse foetal outcomes. Cumulative assessment of OS and AGMs may provide diagnostic usefulness for distinguishing PE with and without FGR.

Differences in the association between midlife hypertension status and late‐life cognition and cognitive change: results from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study

AbstractBackgroundThis study evaluates the association of midlife hypertension status and domain‐specific late‐life cognitive change allowing for possible differences by sex.MethodThe Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort is a multi‐ethnic study of 1,712 Kaiser Permanente Northern California members age 65+ at enrollment in 2017. For 1,696 participants, we categorized the last examined clinical blood pressure measures from 1964‐1985 (mean age = 37.5) as hypotensive, normotensive, prehypertensive, or hypertensive. Verbal episodic memory and executive function were assessed using Spanish and English Neuropsychological Assessment Scales across three interview waves over 4 years and scores were z‐standardized to the baseline. Sex‐stratified linear mixed models with random intercepts estimated the associations of midlife hypertension status with domain‐specific baseline cognition and cognitive change using years since baseline as timescale. Models adjusted for age at blood pressure measurement, KHANDLE baseline age, race, ethnicity, education, practice effects, and interview mode (phone vs in‐person).ResultA greater proportion of men than women had midlife pre‐hypertension (44% vs 31%) or hypertension (21% vs 11%) (Table 1). Among men and women, midlife hypertension status was not associated with baseline executive function or verbal episodic memory (Table 2). Compared to men with normal midlife blood pressure, those with midlife hypotension (b = ‐0.10, 95% CI: ‐0.17, ‐0.04) or midlife hypertension experienced steeper declines in executive functioning (b = ‐0.05, 95% CI: ‐0.10, ‐0.004). Among women, only midlife hypertension was associated with decline in executive function (b = ‐0.04 95% CI: ‐0.09, 0.003), though not significantly different from normotensive women. Compared to normotensive men, those with midlife hypotension (b = ‐0.17, 95%CI: ‐0.27, ‐0.07) and those with pre‐hypertension (b = ‐0.06, 95% CI: ‐0.12, ‐0.004) experienced steeper decline in verbal episodic memory. Among women, only midlife hypertension was associated with steeper declines executive function (b = ‐0.04, 95% CI: ‐0.09, 0.003), though not significantly different from normotensive women. Though effect estimates of midlife hypertension status on cognitive outcomes differed by sex, these differences were not statistically significant.ConclusionBoth hypotension and hypertension 30‐50 years prior to cognitive assessments predicted accelerated cognitive decline in older men. Patterns were less consistent for women but not statistically distinguishable from associations among men.

Comparing Troponin I Level between Preeclampsia and Normotensive Pregnant women

Comparing Troponin I Level between Preeclampsia and Normotensive Pregnant women

The evaluation of maternal serum glycodelin level as a marker for the presence and severity of preeclampsia

Abstract Background: Preeclampsia (PE) is a common multisystemic disorder of pregnancy. Glycodelin is a glycoprotein belongs to the lipocalin superfamily. It acts as a regulator of immunosuppression activity, fertilization, implantation, and placentation. Objectives: To analyze serum glycodelin levels in PE and evaluate whether it correlates with the severity of the disease. Materials and Methods: A prospective case–control study included 60 women diagnosed with PE (subdivided into 30 pregnant women with mild PE and 30 pregnant women with severe PE) and 30 healthy normotensive pregnant women. Patient with multiple pregnancies, gestational trophoblastic diseases, in active labor, a history of medical diseases, or taking treatment were excluded from the study. Blood samples were taken for biochemical study; serum glycodelin levels were measured using an enzyme-linked immunosorbent assay. Results: Patients with PE had significantly higher mean glycodelin levels as compared to the normal group. The glycodelin level ≥37.9 ng/mL had 96.70% sensitivity, 100% specificity, and 98% accuracy for the prediction of PE. The mean glycodelin was significantly higher in severe PE (102.3 ± 51.3) as compared to mild PE (45.2 ± 7.3) in pregnant women (P &lt; 0.001). The glycodelin level ≥50.1 ng/mL had 86.7% sensitivity, 80% specificity, and 85% accuracy for the prediction of severe PE. Conclusions: Glycodelin is an appropriate marker for the diagnosis of PE and the categorization of disease according to severity.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study

BackgroundPrevious evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women.MethodsThe study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records.ResultsThe mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001–0.028).ConclusionHigher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Comparative Study on Serum Calcium in Pre-Eclampsia and Non Pregnant Women

Introduction: There are many Hypertensive disorders in pregnancy like preeclampsia, eclampsia etc. Pre-eclampsia is the most common medical complication of pregnancy associated with increased maternal and infant mortality and morbidity. Some studies have implicated that low serum calcium levels may have a role in pre-eclampsia but other studies failed to find relation between low levels of these trace elements and pre-eclampsia. Objectives:​To evaluate serum calcium in pre-eclampsia &amp; non pregnant women. Materials and Methods: ​This cross sectional study was carried out in among 31 pre-eclampsia patients, aged 20 to 40 years, and gestational age ranges from 20 to40 weeks and 31 age matched normotensive non-pregnant women having no proteinuria. Serum calcium was measured by Colorimetric method. Results:The mean serum calcium level was 5.91 (±2.12) mg/dl in pre–eclampsia and was 5.72 (±2.46) mg/dl in normal women. Conclusion The mean serum calcium level did not differ significantly between the subjects of pre–eclampsia and normal women (t=0; p&lt;.05). The means of both data sets are equal so we can conclude that there is no significant difference between them. Medicine Today 2023 Vol.35(2): 121-123

Placental progesterone and its receptor in HIV-infected pre-eclamptic women

Given the high prevalence of HIV infection and pre-eclampsia (PE) in South Africa, this study evaluated and compared the placental immunostaining of progesterone (P) and progesterone receptors (PR) in the synergy of HIV-infected PE compared to normotensive pregnant women using immunohistochemistry interfaced with morphometric image analysis. Progesterone immunostaining was expressed widely across exchange and conducting villi within mesenchymal, endothelial, and trophoblast cells. In contrast, PR was expressed within syncytiotrophoblasts and was absent within endothelial cells. In exchange villi, P and PR immuno-expression was significantly lower in PE compared to the normotensive group (p = < 0.0001 and p = < 0.0001, respectively) and within the early-onset pre-eclampsia (EOPE) compared to the late-onset pre-eclampsia (LOPE) group (p = < 0.0001 and p = < 0.0001, respectively). Progesterone immuno-expression was significantly lower in the HIV+ compared to the HIV− group (p = < 0.0001), whilst PR was non-significant. In conducting villi, P and PR immuno-expression was significantly lower in the EOPE compared to the LOPE group (p = < 0.0001 and p = < 0.0001, respectively) and in the HIV+ compared to the HIV− group (p = < 0.0001 and p = 0.0009, respectively). Progesterone immuno-expression was slightly higher in the PE compared to normotensive group, and PR immuno-expression was non-significant. There was a significant difference between P and PR within exchange versus conducting villi regardless of pregnancy type, with villi type accounting for 34.47% and 15.28% of total variance for P and PR, respectively. Placental P and PR immuno-expression is downregulated in the duality of PE and HIV+ infection. The use of combined antiretroviral therapy (cART) may result in defective P synthesis, which causes insufficient binding to its receptors. Consequently, PI3K/AKT, JAK-STAT, and MAPK signalling pathways are affected, impairing trophoblast invasion and leading to pre-eclampsia development. Notably, the decrease in P and PR immuno-expression in EOPE validates their effect on placentation.

Utilidad de la relación calcio/magnesio en el diagnóstico de preeclampsia

Objective: To establish the usefulness of the calcium/magnesium ratio in the diagnosis of preeclampsia. Methods: A case-control study was performed between January 2014 and June 2022 on patients who were treated at the Central Hospital “Dr. Urquinaona”, Maracaibo, Venezuela. A group of pregnant women with a diagnosis of preeclampsia (group A, cases) and a control group of pregnant women with maternal age and body mass index similar to the study group (group B, controls) were selected. Demographic characteristics, laboratory parameters, and serum calcium and magnesium concentrations were evaluated. Results: 515 pregnant women were selected, 257 in group A and 258 in group B. Patients in group A had lower serum calcium and magnesium concentrations compared to patients in group B. The calcium/magnesium ratio was also lower in group A than in group B. (p &lt; 0.0001). Analysis of the discriminatory ability of the calcium/magnesium ratio in the diagnosis of preeclampsia showed that the value of 3.44 had a value under the curve of 0.893 (95% confidence interval, 0.867–0.919) with a sensitivity of 66.3% (95%CI, 60.3%-71.8%), specificity 92.6% (95%CI, 88.7%-95.2%). The diagnostic accuracy was 79.4% (95% CI,75.7%–82.7%). Conclusion: The calcium/magnesium ratio is useful in the diagnosis of preeclampsia since its value is significantly lower, compared to healthy normotensive pregnant women.

Highlights of three metabolites HDL and reduction in blood pressure values after dietary fiber supplementation in overweight and obese normotensive women: a metabolomic study

IntroductionThe prevalence of hypertension and obesity are a worldwide concern.ObjetivesAssess the metabolites profile after intervention with mixed dietary fiber in overweight and obese normotensive women.MethodsThis is a randomized double blind placebo-controlled study. Through a simple randomization process, two groups were allocated, with eleven women (group 1) receiving 12 g of mixed dietary fiber and thirteen women (group 2) receiving 12 g of placebo (corn starch) for eight weeks. Anthropometric and biochemical tests and lifestyle were analyzed. As for evaluation metabolomics, used a 1H NMR. The data matrix generated 96 samples and 225 variables, which was exported in the ASCII format for the “The Unscrumbler” statistics software (version 9.7, CAMO Process).ResultsAfter the intervention with mixed dietary fiber, significant differences were observed between the main types of metabolites, referring to the increase in the relative peak areas of in three HDL metabolites 4.94 ppm (0.0086*), HDL 1.28 ppm (0 .0337*), HDL 0.88 ppm (0.0224*) and an α-glucose metabolite 4.90 ppm (0.0106) and the reduction in systolic blood pressure (SBP) (0.0292*) of 7 mmHg in the reference range and in the placebo group there was a reduction in SBP (0.0118*) of 4 mmHg and of a choline metabolite 3.65 ppm (0.0266*), which does not call into question the validity of these results in the literature.ConclusionThe synergism of the functions of these statistically highlighted metabolites contributed to prevention the increase in SBP after fiber intervention in overweight and obese normotensive women.

Association between preeclampsia and long-term risk of arrhythmias

Abstract Background Preeclampsia (PE), a pregnancy-induced hypertensive disorder, affects 4-5% of pregnancies worldwide. It is well known that hypertension is associated with increased risk of arrhythmias; however, data on the association between PE and arrhythmias are sparse and there is a lack of knowledge on the long-term risk of arrhythmias. Purpose To compare the incidence of arrhythmias following preeclamptic and normotensive pregnancies. Methods In this observational cohort study, we identified all primiparous women without history of arrhythmias who gave birth in Denmark from 1997 to 2016 using Danish nationwide registries. The women were stratified on whether they developed PE during their primiparous pregnancy and were followed from primiparous pregnancy to incident arrhythmia, emigration, death, or end of study (December 31, 2018). The comparative risks of arrhythmias were assessed in cause-specific Cox regression analyses adjusted for known arrhythmogenic risk factors including obesity, smoking, hypertension, coronary artery disease, cardiomyopathy, congenital heart disease, thyroid disease, diabetes, and alcohol abuse. Results A total of 521,517 primiparous women with a median age of 28 years were included and 23,523 (4.5%) were diagnosed with PE. Women with versus without PE were of similar age but had a higher burden of comorbidities. During a median follow-up period of 10.2 years, women with PE were associated with higher absolute incidences of arrhythmias (Figure 1). No statistically significant association was found for the composite of cardiac arrest, ventricular arrhythmias, or ICD-implantation nor for the composite of advanced 2nd or 3rd degree atrioventricular block, sinoatrial dysfunction, or pacemaker-implantation. However, women with PE were associated with a significant increased risk of the composite of supraventricular tachyarrhythmias and extrasystoles (p&amp;lt;0.01) and the composite of all included arrhythmias (p&amp;lt;0.01). Factors associated with arrhythmias among women with PE included obesity (HR 1.40 (95%CI 1.03-1.91), coronary artery disease (HR 2.39 (95%CI 1.14-5.00), cardiomyopathy (HR 9.65 (95%CI 3.46-26.92), and congenital heart disease (HR 5.86 (95%CI 2.59-13.28). Conclusion Preeclamptic women were associated with a significantly higher rate of arrhythmias - mainly driven by supraventricular tachyarrhythmias and extrasystoles - than normotensive women. For the purpose of primary and secondary prevention, this finding suggests that women with a history of PE may benefit from evaluation of cardiovascular risk factors, screening of and education in prevention of cardiovascular disease.Figure 1

Should women have lower thresholds for hypertension? Severe ultrastructural abnormalities in systemic arterioles of normotensive and hypertensive women

Abstract Background Hypertension in women is increasingly recognized to originate in the pre-menopause, but the factors that may affect the greater blood pressure increments observed in premenopausal women compared to age-matched men are understudied. Uterine fibroids, occurring in 30-50% of all women, are a strong sex-specific factor associated with hypertension and early cardiovascular events, but the nature of this association is not known. To assess a possible shared pathology of smooth muscle, we studied the ultrastructure of systemic resistance arteries of women with fibroids. Methods Resistance-sized arteries (200 to 400 μm) were harvested from omental samples obtained during fibroid surgery. Transmission electron microscopic images were taken at different magnifications and locations of the vessel wall to assess qualitative and morphological characteristics. Mean blood pressure was calculated as DBP+1/3(SBP-DBP). Results Resistance arteries of 17 women (8 hypertensive, 4 treated), mean age 42 (SE 1) y, were available for analysis. None had a history of cardiovascular disease. Mean blood pressure was 91.4 mm Hg in normotensives and 119.4 in hypertensives. The endothelium showed mitochondrial and endoplasmic reticulum stress in normotensives (Figure, Panel A), to necrosis and sloughing in hypertensives (B). Myocyte-like cells were observed to migrate across the internal elastic lamina, forming small aggregates of subendothelial myocytes in normotensives (C), and larger subendothelial myo-intimal "cushions" in hypertensives (D). Medial myocytes of all patients showed abnormalities similar to fibroids, with dilated sarco-endoplasmic reticulum, elongated mitochondria and myofilament loss involving focal areas or entire cells (E, clinically considered normotensive). Untreated hypertensives had a significantly higher intima-media thickness-to-lumen ratio (%) than normotensives and treated hypertensives as expected, respectively 15.9 (1.8), 12.5 (1.6) and 13.4 (2.1). Conclusion To our knowledge the first ultrastructure data of systemic resistance-sized arteries in women with fibroids, show that young premenopausal women considered clinically normotensive already have severe microvascular abnormalities that may cause or reflect perturbations in microvascular function and predispose to early end organ damage. While there is abundant clinical evidence that the association between blood pressure and cardiovascular events is stronger in women, hypertension in women is understudied. In particular women-specific risk factors are ill-understood. Our observations are relevant to the current discussion regarding whether the clinical threshold for hypertension treatment is too high for women and whether earlier management of cardiovascular risk is needed. Further studies are warranted in a woman-specific research agenda on cardiovascular risk factors in younger premenopausal women.Figure

Exploring the interactive effects of oral contraceptive use and dietary fat intake on blood pressure, cardiovascular reactivity, and glucose tolerance in normotensive women.

Objective: To understand how dietary fat consumption and the use of oral contraceptives interact to affect blood pressure, cardiovascular reactivity, and glucose tolerance in normotensive women. Study Design: Cross-section study. Setting: Hayatabad Medical Complex, Peshawar. Period: December 2022 to April 2023. Material &amp; Methods: A total of 120 normotensive women aged between 18 and 35 years were recruited from local healthcare centers, clinics, and educational institutions. Demographic characteristics, oral contraceptive use, and dietary fat intake were assessed through self-reporting and validated food frequency questionnaires. Resting blood pressure measurements, cardiovascular reactivity during standardized stressors, and glucose tolerance through oral glucose tolerance tests were recorded. Results: The study found no significant associations between oral contraceptive use and blood pressure, cardiovascular reactivity, or glucose tolerance. Similarly, dietary fat intake did not significantly influence these health parameters. Conclusion: The results emphasize the importance of personalized healthcare recommendations for women using oral contraceptives, considering individual variations and other lifestyle factors. Further research with larger, longitudinal studies is warranted to elucidate the potential long-term effects of these interactions and promote cardiovascular health for women worldwide.

The investigation of serum nectin-4 levels in patients with early onset preeclampsia

Aims: We aimed to investigate the level and predictive value of soluble nectin-4 in early onset preeclampsia (EOPE).&#x0D; Methods: Forty-three patients with EOPE and 41 healthy normotensive pregnant women participated in this prospective case-control study. The groups were matched for gestational age and gravidity. Serum nectin-4 levels were compared between groups. The ROC curve was drawn to show the predictive value of nectin-4 for EOPE. Patients were followed up until the end of labor, and perinatal outcomes were recorded.&#x0D; Results: The demographic characteristics of the two groups were similar. Serum nectin-4 level was significantly increased in EOPE cases compared to controls (226.46±119.6 ng/ml vs. 156.54±44.8 ng/ml, p=0.001). The ROC showed that at &gt; 160.938, the sensitivity and specificity were 67.44% and 82.93%, respectively [AUC:0.822, (CI:0.724 - 0.897), and (p&lt; 0.001)]. Significant inverse correlations were found between nectin-4 levels and poor obstetric outcomes.&#x0D; Conclusion: Maternal serum nectin-4 levels were significantly higher in patients with EOPE compared with controls. Increased nectin-4 levels may contribute to the development of EOPE through possible oxidative, immunological, and inflammatory mechanisms adversely affecting trophoblastic cells.

A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy

Background and aimsObesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. Methods and resultsThirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. ConclusionsOur study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.