Female-specific risk variables: From innocent bystanders to key players in cardiovascular risk prediction.

There is an increasing interest among professionals in cardiovascular medicine in women-specific risk variables related to gynecologic conditions over the life span. Although adverse lifestyle factors, hypertension, dyslipidemia and insulin resistance are recognized as the most important risk factors in older women, there is still uncertainty over how to account for other risk variables. For instance, migraine from puberty onwards, chronic inflammatory conditions and mental stress affect cardiovascular risk in women. As prevention should start as early in life as possible, appropriate risk estimation in women at middle age is crucial. In case of doubt, a coronary artery calcium score with a computed tomography scan at a radiology department can be helpful to discriminate between low and high risk for an individual. This may also pave the way for safe menopausal hormone therapy if needed. In this paper we summarize the current status of women-specific and other relevant risk variables from the perspective of the cardiologist.

Pregnancy-associated changes in urinary uromodulin excretion in chronic hypertension.

BACKGROUND: Pregnancy involves major adaptations in renal haemodynamics, tubular, and endocrine functions. Hypertensive disorders of pregnancy are a leading cause of maternal mortality and morbidity. Uromodulin is a nephron-derived protein that is associated with hypertension and kidney diseases. Here we study the role of urinary uromodulin excretion in hypertensive pregnancy. METHODS: Urinary uromodulin was measured by ELISA in 146 pregnant women with treated chronic hypertension (n = 118) and controls (n = 28). We studied non-pregnant and pregnant Wistar Kyoto and Stroke Prone Spontaneously Hypertensive rats (n = 8/strain), among which a group of pregnant Stroke-Prone Spontaneously Hypertensive rats was treated with either nifedipine (n = 7) or propranolol (n = 8). RESULTS: In pregnant women, diagnosis of chronic hypertension, increased maternal body mass index, Black maternal ethnicity and elevated systolic blood pressure at the first antenatal visit were significantly associated with a lower urinary uromodulin-to-creatinine ratio. In rodents, pre-pregnancy urinary uromodulin excretion was twofold lower in Stroke-Prone Spontaneously Hypertensive rats than in Wistar Kyoto rats. During pregnancy, the urinary uromodulin excretion rate gradually decreased in Wistar Kyoto rats (a twofold decrease), whereas a 1.5-fold increase was observed in Stroke-Prone Spontaneously Hypertensive rats compared to pre-pregnancy levels. Changes in uromodulin were attributed by kidney injury in pregnant rats. Neither antihypertensive changed urinary uromodulin excretion rate in pregnant Stroke-Prone Spontaneously Hypertensive rats. CONCLUSIONS: In summary, we demonstrate pregnancy-associated differences in urinary uromodulin: creatinine ratio and uromodulin excretion rate between chronic hypertensive and normotensive pregnancies. Further research is needed to fully understand uromodulin physiology in human pregnancy and establish uromodulin's potential as a biomarker for renal adaptation and renal function in pregnancy.

Analysis of Clinical Profiles and Echocardiographic Cardiac Outcomes in Peripartum Cardiomyopathy (PPCM) vs. PPCM with Co-Existing Hypertensive Pregnancy Disorder (HPD-PPCM) Patients: A Systematic Review and Meta-Analysis.

Peripartum cardiomyopathy (PPCM) is a form of new-onset heart failure that has a high rate of maternal morbidity and mortality. This was the first study to systematically investigate and compare clinical factors and echocardiographic findings between women with PPCM and co-incident hypertensive pregnancy disorders (HPD-PPCM) and PPCM-only women. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) framework. We used four databases and a single search engine, namely PubMed/Medline, Scopus, Web of Science, and Cochrane. We used Cochrane Risk of Bias (RoB) 2.0 for quality assessment. Databases were searched for relevant articles published from 2013 to the end of April 2023. The meta-analysis used the DerSimonian-Laird random-effects model to analyze the pooled mean difference (MD) and its p-value. We included four studies with a total of 64,649 participants and found that systolic blood pressure was significantly more likely to be associated with the PPCM group than the HPD-PPCM group (SMD = -1.63) (95% CI; -4.92,0.28, p = 0.01), while the other clinical profiles were not significant. HPD-PPCM was less likely to be associated with LVEF reduction (SMD = -1.55, [CI: -2.89, -0.21], p = 0.02). HPD-PPCM was significantly associated with less LV dilation (SMD = 1.81; 95% (CI 0.07-3.01), p = 0.04). Moreover, HPD-PPCM was less likely to be associated with relative wall thickness reduction (SMD = 0.70; 95% CI (-1.08--0.33), p = 0.0003). In conclusion, PPCM and HPD-PPCM shared different clinical profiles and remodeling types, which may affect each disease's response to pharmacological treatment. Patients with HPD-PPCM exhibited less eccentric remodeling and seemed to have a higher chance of recovering their LV ejection fraction, which means they might not benefit as much from ACEi/ARB and beta-blockers. The findings of this study will guide the development of guidelines for women with PPCM and HPD-PPCM from early detection to further management.

Peripartum Maternal Admission to the Intensive Care Unit: An Observational Study over a 15-Year Period at a Tertiary Center in Austria.

Peripartum maternal admission to the intensive care unit is challenging for anesthesiologists, obstetricians, and all personnel involved. An understanding of altered maternal physiology, fetal considerations, and acute peripartum emergencies is required to ensure adequate maternal and neonatal outcomes. In this study, we analyzed data of peripartum maternal admissions to the intensive care unit at our large tertiary referral center in order to define trends and changes over time. This study retrospectively analyzed maternal morbidity, admission diagnoses, treatments, and outcomes of women with peripartum admission to the intensive care unit at our tertiary care center over a 15-year period. We found that patient characteristics and admission diagnoses remained remarkably consistent over the observational period; however, there was a significant increase in postpartum hemorrhage (r = 0.200, p < 0.001) and cesarean hysterectomy (r = 0.117, p = 0.027) over time. Moreover, we found a reduction in preterm births (r = -0.154, p = 0.004) and a decreased peripartum neonatal intensive care unit admission rate (r = -0.153, p = 0.006) among women who were transferred to the intensive care unit. Based on our long-term observational data, there is consistent need for intensive care in obstetrics due to a small number of different etiologies. Specialized training for the predominant diagnoses involved as well as multidisciplinary care of the affected patients are both warranted.

New advances in prediction and surveillance of preeclampsia: role of machine learning approaches and remote monitoring.

Preeclampsia, a multisystem disorder in pregnancy, is still one of the main causes of maternal morbidity and mortality. Due to a lack of a causative therapy, an accurate prediction of women at risk for the disease and its associated adverse outcomes is of utmost importance to tailor care. In the past two decades, there have been successful improvements in screening as well as in the prediction of the disease in high-risk women. This is due to, among other things, the introduction of biomarkers such as the sFlt-1/PlGF ratio. Recently, the traditional definition of preeclampsia has been expanded based on new insights into the pathophysiology and conclusive evidence on the ability of angiogenic biomarkers to improve detection of preeclampsia-associated maternal and fetal adverse events.However, with the widespread availability of digital solutions, such as decision support algorithms and remote monitoring devices, a chance for a further improvement of care arises. Two lines of research and application are promising: First, on the patient side, home monitoring has the potential to transform the traditional care pathway. The importance of the ability to input and access data remotely is a key learning from the COVID-19 pandemic. Second, on the physician side, machine-learning-based decision support algorithms have been shown to improve precision in clinical decision-making. The integration of signals from patient-side remote monitoring devices into predictive algorithms that power physician-side decision support tools offers a chance to further improve care.The purpose of this review is to summarize the recent advances in prediction, diagnosis and monitoring of preeclampsia and its associated adverse outcomes. We will review the potential impact of the ability to access to clinical data via remote monitoring. In the combination of advanced, machine learning-based risk calculation and remote monitoring lies an unused potential that allows for a truly patient-centered care.

COVID-19, lifestyle behaviors and mental health: A mixed methods study of women 6 months following a hypertensive pregnancy.

Introduction: The COVID-19 pandemic introduced unprecedented challenges to both the physical and psychological health of postpartum women. The aim of this study was to determine how the COVID-19 pandemic affected the diet, physical activity and mental health of women 6 months following a hypertensive disorder of pregnancy. Methods: Mixed methods sub-study of the Blood Pressure Postpartum trial, which recruited women following a hypertensive disorder of pregnancy from six Sydney metropolitan hospitals. Cross sectional analysis of baseline quantitative data, collected at 6-months postpartum from March 2019-February 2022, and qualitative data analysis from semi-structured telephone interviews, was performed. Dates of COVID-19 lockdowns for Sydney, Australia were collected from government websites. Diet (vegetable, fruit, alcohol, take away intake) and physical activity (walking, vigorous activity, strength training frequency and duration) were assessed using the self-report NSW Population Health Survey. Depression and anxiety were assessed using the Edinburgh Depression Scale and GAD-7 scale, respectively. Outcome data were compared between women who completed surveys "In Lockdown" vs. "Not in Lockdown" as well as "Prior to any Lockdown" vs. "During or Following any Lockdown". Results: Of 506 participants, 84 women completed the study surveys "In Lockdown," and 149 completed the surveys "Prior to any Lockdown." Thirty-four participants were interviewed. There were no statistically significant differences in diet, physical activity, depression and anxiety among women who completed the survey "In Lockdown" vs. "Not in Lockdown." "Prior to any Lockdown," participants were more likely to do any walking (95% vs. 89%, p = 0.017), any vigorous activity (43% vs. 30%, p = 0.006) or any strength training (44% vs. 33%, p = 0.024), spent more time doing vigorous activity (p = 0.003) and strength training (p = 0.047) and were more likely to drink alcohol at least monthly (54% vs. 38%, p < 0.001) compared with "During or Following any Lockdown." Conclusions: Our findings suggest that the confinements of lockdown did not markedly influence the mental health, diet and physical activity behaviors of women 6 months following hypertensive pregnancy. However, physical activity levels were reduced following the emergence of COVID-19, suggesting targeted efforts may be necessary to re-engage postpartum women with exercise. Trial registration: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376286&isReview=true, identifier: ACTRN12618002004246.

Decrease in Nitric Oxide Production as a Key Mediator in the Pathogenesis of Preeclampsia and a Potential Therapeutic Target: A Case-Control Study.

Pregnancy-induced hypertension (GH) complicates 6−10% of all pregnancies and, in 2019, was responsible for approximately 28,000 deaths. The most common cause of gestational hypertension is pre-eclampsia (PE), which afflicts 2−8% of all pregnancies and is one of the three leading causes of maternal morbidity and mortality worldwide. The aim of this study was to clarify how NO metabolism changes during the course of PE. Due to the short half-life of NO, we measured the concentrations of its stable metabolites, nitrite and nitrate (NOx). Out of 100 enrolled patients: 58 pregnant women with a diagnosed early form of PE formed a study group, and 42 healthy pregnant women formed a control group. NOx concentrations were significantly lower in the PE group than in the control group, with mean values of 5.33 and 27.64 µmol/L, respectively (p < 0.0001). The decrease in NO is most likely the result and mediator of systemic endothelial dysfunction. The impairment of NO metabolism in PE appears to play an important role in its pathogenesis. Therefore, it is a potential therapeutic target.

Soluble urinary somatic angiotensin converting enzyme is overexpressed in patients with preeclampsia: a potential new marker for the disease?

OBJECTIVE: The aim of this study was to identify and quantify urinary Angiotensin-Converting-Enzyme (ACE) in hypertensive disorders of pregnancy. METHODS: Urine samples were analyzed by Western blot. Patients were classified into: normotensive pregnancy (N); preeclampsia and superimposed preeclampsia (PE+SPE); and gestational hypertension (GH). RESULTS: Somatic ACE protein expression was higher in PE+SPE compared to N and GH. There was a positive correlation between ACE and urinary protein to creatinine ratio, systolic and diastolic blood pressures. CONCLUSION: These results indicate ACE overexpression in the urine of preeclamptic patients and suggest that it may be a new marker for the disease.

A review of infant growth and psychomotor developmental outcomes after intrauterine exposure to preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy with serious health implications for mother and their offspring. The uteroplacental vascular insufficiency caused by preeclampsia is associated with epigenetic and pathological changes in the mother and fetus. However, the impact of preeclampsia in infancy (birth to 2 years), a time of rapid development influenced by pre- and postnatal factors that can predict future health outcomes, remains inconclusive. This narrative review of 23 epidemiological and basic science studies assessed the measurement and impact of preeclampsia exposure on infant growth and psychomotor developmental outcomes from birth to 2 years. Studies assessing infant growth report that preeclampsia-exposed infants have lower weight, length and BMI at 2 years than their normotensive controls, or that they instead experience accelerated weight gain to catch up in growth by 2 years, which may have long-term implications for their cardiometabolic health. In contrast, clear discrepancies remain as to whether preeclampsia exposure impairs infant motor and cognitive development, or instead has no impact. It is additionally unknown whether any impacts of preeclampsia are independent of confounders including shared genetic factors that predispose to both preeclampsia and childhood morbidity, perinatal factors including small for gestational age or preterm birth and their sequelae, and postnatal environmental factors such childhood nutrition. Further research is required to account for these variables in larger cohorts born at term, to help elucidate the independent pathophysiological impact of this clinically heterogenous and dangerous disease.

No accelerated arterial aging in relatively young women after preeclampsia as compared to normotensive pregnancy.

Introduction: Preeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s). Methods: Data was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models. Results: Of the 1,217 included women (age range 22-62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: -0.48%/10 years (95% CI:-0.65 to -0.30%/10 years), NGMD: -1.13%/10 years (-1.49 to -0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls (p-values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD. Conclusion: In young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries.

Corrigendum: The P4 Study: Postpartum Maternal and Infant Faecal Microbiome 6 Months After Hypertensive Versus Normotensive Pregnancy.

[This corrects the article DOI: 10.3389/fcimb.2022.646165.].

The P4 Study: Postpartum Maternal and Infant Faecal Microbiome 6 Months After Hypertensive Versus Normotensive Pregnancy.

OBJECTIVE/HYPOTHESIS: To explore potential differences in faecal microbiome between women, and their infants, who had normotensive pregnancies (NP) and those who had a hypertensive pregnancy (HP), either gestational hypertension (GH) or preeclampsia (PE). METHODS: This is a sub study of P4 (Postpartum Physiology, Psychology, and Paediatrics Study) and includes 18 mother-infant pairs: 10 NP and 8 HP (HP as defined by blood pressure > 140/90mmHg; of which 6 had PE, and 2 GH), six months postpartum. The participating mothers collected stool samples from themselves and their infants. 16S rRNA V3-V4 amplicons were used to study the faecal microbiome. RESULTS: The sample of women and their infants were mostly primiparous (n =16) with vaginal birth (n = 14). At the time of faecal sampling 8 women were using hormonal contraception, and one HP woman remained on an antihypertensive. All women had blood pressure < 130/80mmHg, and 10 had high BMI (> 30). All infants had started solids, 8 were exclusively breastfed, 1 exclusively formula fed and 9 both. Three infants had been exposed to a course of antibiotics. Six months postpartum, there were no significant differences in alpha or beta diversity between the gut microbiota of HP and NP women (P > 0.05). However, a statistically significant difference was detected in alpha diversity between infants following HP and NP, with lower diversity levels in HP infants (P < 0.05). It was also found that at a genus and species level, the gut microbiota of HP women was enriched with Bifidobacterium and Bifididobacterium sp. and depleted in Barnisiella and Barnesiella intestinihominis when compared to NP women (P < 0.05). Similarly, the gut microbiota of infants born from HP was enriched in Streptococcus infantis and depleted in Sutterella, Sutterella sp., Bacteroides sp. and Clostridium aldenense compared to infants born from NP (P < 0.05). DISCUSSION: While our findings are at best preliminary, due to the very small sample size, they do suggest that the presence of hypertension in pregnancy may adversely affect the maternal microbiota postpartum, and that of their infants. Further analysis of postpartum microbiome data from future studies will be important to validate these early findings and provide further evidence about the changes in the microbiota in the offspring of women following hypertensive disorders of pregnancy (HDP), including possible links to the causes of long-term cardiovascular disease, the prevalence of which is increased in women who have experienced HDP.

High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration.

Placentas from preeclamptic women display augmented tumor necrosis factor-alpha (TNF-α) levels with reduced expression of aquaporin 3 (AQP3). However, whether TNF-α modulates AQP3 expression remains to be elucidated. We hypothesize that elevated levels of TNF-α reduce AQP3 expression and negatively impact trophoblastic cell migration. Spontaneously hypertensive rats (SHRs) and Wistar rats (14-16 weeks) were divided into hypertensive and normotensive groups, respectively. Systolic blood pressure (SBP) was measured, and animals mated. In a third group, pregnant SHRs were treated with a TNF-α antagonist, etanercept (0.8 mg/kg, subcutaneously) on days 0, 6, 12, and 18 of pregnancy. Placentas were collected on the 20th day of pregnancy. Human placental explants, from normotensive pregnancies, were incubated with TNF-α (5, 10, and 20 ng/ml) and/or etanercept (1 µg/ml). Swan 71 cells were incubated with TNF-α (10 ng/ml) and/or etanercept (1 µg/ml) and subjected to the wound healing assay. AQP3 expression was assessed by Western blot and TNF-α levels by ELISA. SBP (mmHg) was elevated in the hypertensive group, and etanercept treatment reduced this parameter. Placental TNF-α levels (pg/ml) were higher in the hypertensive group. AQP3 expression was reduced in the hypertensive group, and etanercept treatment reversed this parameter. Explants submitted to TNF-α exposition displayed reduced expression of AQP3, and etanercept incubation reversed it. Trophoblastic cells incubated with TNF-α showed decreased cell migration and reduced AQP3 expression, and etanercept incubation ameliorated it. Altogether, these data demonstrate that high TNF-α levels negatively modulate AQP3 in placental tissue, impairing cell migration, and its relationship in a pregnancy affected by hypertension.

The Immediate and Long-Term Impact of Preeclampsia on Offspring Vascular and Cardiac Physiology in the Preterm Infant.

Hypertensive disorders of pregnancy, including preeclampsia, affect nearly 10% of all pregnancies and are associated with significant long-term detrimental effects on both maternal and offspring cardiovascular health. Current management of preeclampsia involves timely delivery with the more severe form of disease requiring iatrogenic preterm birth. The effects on the maternal cardiovascular system have been studied extensively; however, less is known about the short- and long-term impacts on offspring cardiovascular health. There is a growing body of evidence suggesting that the offspring of pre-eclamptic pregnancies have an altered cardiac structure and function, along with a unique vascular physiology driven by lower endothelial function. Many of these changes can also be seen in those born preterm even in the absence of pregnancy hypertension. It is difficult to determine the relative contribution of pre-maturity and preeclampsia to the cardiovascular phenotype of those exposed to these pregnancy complications as they are, in many cases, inextricably linked. This review, therefore, focuses specifically on the evidence from clinical studies showing a negative cardiovascular impact of preeclampsia in preterm-born offspring, investigating phenotypic similarities and differences between offspring born preterm to normotensive vs. pre-eclamptic pregnancies. We explore the unique cardiac and vascular alterations in pre-eclamptic offspring born preterm, highlighting knowledge gaps, and potential areas of further research in the field.

Short term cardiovascular risk in normotensive women after hypertensive pregnancy / Riesgo cardiovascular a corto plazo en mujeres normotensas tras trastorno hipertensivo del embarazo

Introduction: Hypertensive pregnancy was recognized as a risk factor of cardiovascular events. The aim of our study was to evaluate the short-term cardiovascular risk in normotensive females with previous hypertensive pregnancy. Material and methods: A prospective cohort study was conducted on 50 females with previous normotensive pregnancy and 50 females with previous hypertensive pregnancy. All patients were re-evaluated three months postpartum to be sure that they became normotensive. One year postpartum, all patients were subjected to renal function tests, urinary albumin/creatinine ratio for microalbuminuria, glycated hemoglobin, complete lipid profile, echocardiographic assessment of left ventricular mass index and carotid duplex for measurement of intimal–medial thickness, presence of carotid plaques and stenosis. Results: No significant difference between both groups regarding blood pressure level three months postpartum. No significant difference between both groups regarding serum creatinine. Patients with previous hypertensive pregnancy group had significantly higher microalbuminuria compared with previous normotensive pregnancy group (p=0.000). Serum LDL and triglycerides were significantly higher however HDL was significantly lower in those with previous hypertensive pregnancy, however all lipid profile measures were within normal range. No significant difference between both groups regarding left ventricular mass index and carotid intima-media thickness. No evidence of carotid plaques or stenosis in both groups. (AU)

Introducción: El trastorno hipertensivo del embarazo ha sido reconocido como un factor de riesgo de episodios cardiovasculares. El objetivo de nuestro estudio fue evaluar el riesgo cardiovascular a corto plazo en mujeres normotensas con trastorno hipertensivo del embarazo previo. Material y métodos: Se realizó un estudio prospectivo de cohorte en 50 mujeres con embarazo normotenso previo y 50 mujeres con trastorno hipertensivo del embarazo. Todas las pacientes fueron re-evaluadas a los 3 meses del parto, para asegurarnos de que eran normotensas. Transcurrido un año del parto, se realizaron pruebas de función renal, albúmina en la orina/ratio de creatinina para microalbuminuria, hemoglobina glucosilada, perfil lipídico completo, valoración ecocardiográfica del índice de masa ventricular izquierda y dúplex carotídeo para medir el grosor íntima-media, presencia de placas carotideas y estenosis, en todas las pacientes. Resultados: No se encontraron diferencias significativas entre ambos grupos en cuanto a nivel de presión arterial, transcurridos 3 meses del parto. No se encontraron diferencias significativas entre ambos grupos en cuanto a creatinina sérica. El grupo de pacientes con trastorno hipertensivo del embarazo tuvo un mayor nivel de microalbuminuria en comparación con el grupo de embarazo normotenso previo (p=0,000). Los niveles séricos de LDL y triglicéridos fueron significativamente mayores, pero el nivel de HDL fue significativamente menor en aquellas mujeres con trastorno hipertensivo del embarazo previo, aunque el perfil lipídico de todas las pacientes se situó en valores normales. No se encontraron diferencias significativas entre ambos grupos en cuanto a índice de masa ventricular izquierda y grosor íntima-media carotideo. No se encontró evidencia de placas carotídeas ni estenosis en ninguno de los grupos. (AU)

Preexisting hypertension and pregnancy-induced hypertension reveal molecular differences in placental proteome in rodents.

Preexisting or new onset of hypertension affects pregnancy and is one of the leading causes of maternal and fetal morbidity and mortality. In certain cases, it also leads to long-term maternal cardiovascular complications. The placenta is a key player in the pathogenesis of complicated hypertensive pregnancies, however the pathomechanisms leading to an abnormal placenta are poorly understood. In this study, we compared the placental proteome of two pregnant hypertensive models with their corresponding normotensive controls: a preexisting hypertension pregnancy model (stroke-prone spontaneously hypertensive rats; SHRSP) versus Wistar-Kyoto and the transgenic RAS activated gestational hypertension model (transgenic for human angiotensinogen Sprague-Dawley rats; SD-PE) versus Sprague-Dawley rats, respectively. Label-free proteomics using nano LC-MS/MS was performed for identification and quantification of proteins. Between the two models, we found widespread differences in the expression of placental proteins including those related to hypertension, inflammation, and trophoblast invasion, whereas pathways such as regulation of serine endopeptidase activity, tissue injury response, coagulation, and complement activation were enriched in both models. We present for the first time the placental proteome of SHRSP and SD-PE and provide insight into the molecular make-up of models of hypertensive pregnancy. Our study informs future research into specific preeclampsia and chronic hypertension pregnancy mechanisms and translation of rodent data to the clinic.

Short term cardiovascular risk in normotensive women after hypertensive pregnancy.

INTRODUCTION: Hypertensive pregnancy was recognized as a risk factor of cardiovascular events. The aim of our study was to evaluate the short-term cardiovascular risk in normotensive females with previous hypertensive pregnancy. MATERIAL AND METHODS: A prospective cohort study was conducted on 50 females with previous normotensive pregnancy and 50 females with previous hypertensive pregnancy. All patients were re-evaluated three months postpartum to be sure that they became normotensive. One year postpartum, all patients were subjected to renal function tests, urinary albumin/creatinine ratio for microalbuminuria, glycated hemoglobin, complete lipid profile, echocardiographic assessment of left ventricular mass index and carotid duplex for measurement of intimal-medial thickness, presence of carotid plaques and stenosis. RESULTS: No significant difference between both groups regarding blood pressure level three months postpartum. No significant difference between both groups regarding serum creatinine. Patients with previous hypertensive pregnancy group had significantly higher microalbuminuria compared with previous normotensive pregnancy group (p=0.000). Serum LDL and triglycerides were significantly higher however HDL was significantly lower in those with previous hypertensive pregnancy, however all lipid profile measures were within normal range. No significant difference between both groups regarding left ventricular mass index and carotid intima-media thickness. No evidence of carotid plaques or stenosis in both groups. CONCLUSIONS: Previous hypertensive pregnancy was associated with increased risk of microalbuminuria at short term level even after normalization of blood pressure post-partum. Longer period of follow up is required to establish the potential cardiovascular risk in these patients.

Maternal macro- and micronutrient intake six months after hypertensive versus normotensive pregnancy: is poor diet quality contributing to future cardiometabolic disease risk?

BACKGROUND: Hypertensive pregnancy is associated with increased long-term cardiometabolic disease risk. Assessing dietary intake patterns after hypertensive (HP) versus normotensive pregnancy (NP) may provide insights into the mechanism of this risk. METHODS: This study was a prospective sub-study of the P4 (Postpartum, Physiology, Psychology and Paediatrics) cohort. Women were studied six months after NP versus HP (preeclampsia or gestational hypertension). Dietary energy, macronutrient and micronutrient intake were measured using a three-day food diary (FoodWorks™) and assessed against Australian and New Zealand Nutrient Reference Values to determine nutritional adequacy. Comparisons between breastfeeding and non-breastfeeding women were assessed, and linear regression modelling (using hypertensive status, breastfeeding status, and demographic/pregnancy variables) performed to assess predictors of energy intake. RESULTS: Seventy-four women (60 NP, 14 HP) were included. HP women had higher mean body mass index (p = 0.02) and lower breastfeeding rates (29% HP versus 83% NP, p < 0.001) compared to NP women. Twenty-four-hour energy intake and total fat intake were 17% and 20% lower after HP respectively. Nutrient deficiencies were prevalent across all participants, however more HP women had inadequate magnesium, calcium and phosphorus intake. Breastfeeding women had significantly increased energy (17%), carbohydrate (15%) and total fat intake (21%), and increased vitamin A, vitamin E, riboflavin, magnesium and iron intake compared to non-breastfeeding women. HP and breastfeeding status were independent predictors of energy intake. CONCLUSIONS: HP women had lower micronutrient intake and greater prevalence of nutritional inadequacy compared to NP women, reflecting poorer diet quality and potentially contributing to future increased cardiometabolic disease risk.

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists.

Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).

Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy are increasing in incidence and are major causes of maternal morbidity and mortality both in the United States and worldwide. An understanding of these diseases is essential for the practicing nephrologist, as preexisting kidney disease is an important risk factor. In addition, the development of hypertensive disorders of pregnancy has important implications for long-term risk of kidney disease and cardiovascular disease. The definition and diagnostic criteria has changed in recent years as our understanding of the disease entity has progressed. Currently, proteinuria is no longer a necessary diagnostic feature of preeclampsia. Preeclampsia and gestational hypertension may develop through multiple different mechanisms. Current research suggests contributions of both placental factors and maternal factors contribute to the disease and represent different phenotypic presentations of preeclampsia.