Patients' understanding of long-term cardiovascular risks and associated health-seeking behaviours after pre-eclampsia.

OBJECTIVE: The lifelong risks of cardiovascular disease following hypertensive disorders of pregnancy are well described. Awareness of these risks and associated health-seeking behaviours among affected individuals remains unclear. We aimed to assess participants' knowledge of their cardiovascular disease risk and relevant health-seeking behaviours following a pregnancy affected by preeclampsia or gestational hypertension. METHODS: We undertook a single-site, cross-sectional cohort study. The target population included individuals who birthed at a large tertiary referral centre in Melbourne, Australia, between 2016 and 2020, and were diagnosed with gestational hypertension or pre-eclampsia. Participants completed a survey assessing pregnancy details, medical comorbidities, knowledge of future risks and health-seeking behaviours post-pregnancy. RESULTS: 1526 individuals met inclusion criteria and 438 (28.6%) completed the survey. Of these, 62.6% (n=237) were unaware of their increased risk of cardiovascular disease following a hypertensive disorder of pregnancy. Participants who reported awareness of their increased risk were more likely to have annual blood pressure monitoring (54.6% vs 38.1%, p<0.01), and at least one assessment of blood cholesterol (p<0.01), blood glucose (p=0.03) and renal function (p=0.01). Participants who were aware were more likely to be taking antihypertensive medication (24.5% vs 6.6%, p<0.01) since pregnancy, compared with those who were unaware. There were no differences between groups in diet, exercise or smoking habits. CONCLUSION: Among our study cohort, risk awareness was associated with increased health-seeking behaviours. Participants who were aware of their increased risk of cardiovascular disease were more likely to have regular cardiovascular risk factor assessments. They were also more likely to be taking antihypertensive medication.

Naringenin prevents pregnancy-induced hypertension via suppression of JAK/STAT3 signalling pathway in mice.

BACKGROUND: Pregnancy-induced hypertension (PIH) is characterized by high blood pressure during pregnancy, which causes perinatal and maternal mortality. Inflammation, oxidative stress and the JAK2/STAT3 signalling pathway have been reported to play critical roles in the pathogenies of PIH. Due to the safety and side effects of current treatments for PIH, searching for new therapeutic agents is urgently needed. Naringenin is a flavonoid with anti-inflammation and anti-oxidation activities. In the current study, the effects of naringenin on PIH were investigated. METHODS: We established the PIH mouse model and administrated naringenin to these mice. The blood pressure, total urine protein, plasma levels of vasodilation converting enzyme (VCE), α-1A adrenergic receptor (α-ADR) and angiotensin, inflammatory cytokines, oxidative stress markers were measured. The protein levels of reactive oxygen species proto-oncogene 1 (ROS1), superoxide dismutase 2 (SOD2), signal transducer and activator of transcription 3 (STAT3), phospho-STAT3, Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), Janus kinase 2 (JAK2) and phospho-JAK2, in vascular endothelium cells were detected by western blot. RESULTS: Administration of naringenin significantly decreased blood pressure, total urine protein level, plasma levels of VCE, α-ADR and angiotensin in PIH mice. Naringenin decreased serum levels of pro-inflammatory cytokines interleukin (IL)-2, IL-6 and tumour necrosis factor alpha (TNF-α), while increased IL-10. Naringenin decreased serum levels of ROS, endothelin while increased SOD and nitric oxide levels. Western blot analysis showed that naringenin inhibited ROS expression, while increased SOD expression in vascular endothelial cells of mice. In addition, western blot also showed that naringenin inhibited JAK2/STAT3 signalling by suppressing SHP-1 expression in vascular endothelial cells of mice. CONCLUSION: Naringenin suppressed the activation of JAK2/STAT3 signalling pathway and promoted SHP-1 expression, leading to ameliorated hypertension in pregnancy.

Crocin exhibits an antihypertensive effect in a rat model of gestational hypertension and activates the Nrf-2/HO-1 signaling pathway.

Gestational hypertension is a leading cause of both prenatal and maternal mortality and morbidity; however, there have been rather limited advances in the management of gestational hypertension in recent years. There has been evidence supporting the antihypertensive properties of crocin, but the specific mechanism is still unclear. N-Nitro-L-arginine methyl ester (L-NAME) was employed to establish a rat model with a preeclampsia-like phenotype, particularly gestational hypertension. Enzyme-linked immunosorbent assays were conducted to determine the levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1); the levels of the circulating cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α; and oxidative stress factors. Quantitative RT-PCR assays were performed to assess the transcript levels of various cytokines in the placenta, and western blot assays were carried out to evaluate the protein levels of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2-like 2 (Nrf-2). Treatment with crocin reduced the blood pressure of rats with gestational hypertension, which was accompanied by suppressed circulating levels of PlGF and sFlt-1. Crocin further alleviated the inflammatory signals and oxidative stress in the serum, as well as in placental tissues, in rats with L-NAME-induced hypertension. Crocin treatment also improved pregnancy outcomes in terms of fetal survival, fetal weight, and the fetal/placental weight ratio. Finally, in hypertension elicited by L-NAME, crocin stimulated the placental Nrf-2/HO-1 pathway. Crocin alleviated inflammatory and oxidative stress in placental tissues, thereby protecting against gestational hypertension, one of the major phenotypes of preeclampsia, and activated the Nrf-2/HO-1 pathway.

Effect of baicalin on gestational hypertension-induced vascular endothelial cell damage.

OBJECTIVE: Baicalin is a compound extracted from the dried root of Scutellaria baicalensis Georgi. Studies have shown that baicalin has a protective effect on vascular endothelial cells, but whether baicalin could alleviate ascular endothelial cell damage in pregnancy-induced hypertensive patients remains unknown. MATERIALS AND METHODS: We established a hypertensive pregnant rat model to study vascular endothelial injury during pregnancy-induced hypertension. Plasma epoprostenol (PGI-2), thromboxane A2 (Txa-2), ß-human chorionic gonadotropin (ß-HCG), and estrogen levels in rats were detected using ELISA. Vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and C-reactive protein (CRP) expression were detected using western blotting and quantitative PCR (q-PCR). RESULTS: Results showed that baicalin alleviated symptoms of pregnancy-induced hypertension. CRP, Txa-2, and ß-HCG expression were significantly upregulated, while VEGF, eNOS, PGI-2, and estrogen expression was decreased in plasma and placental tissues of hypertensive rats. However, the levels of these injury indicators were significantly decreased after baicalin therapy, while the expression of protective indicators was significantly increased. CONCLUSION: Baicalin reversed vascular endothelial cell injury in pregnant hypertensive rats by promoting VEGF, eNOS, PGI-2, and estrogen expression.

Quercetin attenuates reduced uterine perfusion pressure -induced hypertension in pregnant rats through regulation of endothelin-1 and endothelin-1 type A receptor.

BACKGROUND: Quercetin was reported to be crucial for a broad range of activities, including attenuating inflammation, platelet aggregation, capillary permeability, and lipid peroxidation. However, the effect of quercetin in hypertension during pregnancy, was not fully understood. METHODS: The model of hypertension in pregnancy was established in rats by reduced uterine perfusion pressure (RUPP). Quercetin was administrated by gavage. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using the CODA 6 BP system. Plasma concentrations of Endothelin-1 (ET-1), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF) were detected using enzyme-linked immunosorbent assay kits. The mRNA and protein levels of ET-1 and endothelin-1 type A receptor (ETAR) were determined by RT-PCR and Western blotting. The ETAR antagonist BQ-123 was performed by osmotic minipumps. RESULTS: In RUPP induced rats, quercetin treatment decreased SBP and DBP, fetal resorptions percentage, plasma ET-1 and sFlt-1 concentrations, ET-1 and ETAR levels, but increased fetal body weight and VEGF expression. BQ-123 administration attenuated SBP and DBP, suppressed fatal resorptions percentage, and increased fetal body weight of RUPP rats. CONCLUSION: Quercetin attenuates RUPP induced hypertension in pregnant rats through the regulation of ET-1 and ETAR.

Changes in the Prevalence of Chronic Hypertension in Pregnancy, United States, 1970 to 2010.

We estimated changes in the prevalence of chronic hypertension among pregnant women and evaluated the extent to which changes in obesity and smoking were associated with these trends. We designed a population-based cross-sectional analysis of over 151 million women with delivery-related hospitalizations in the United States, 1970 to 2010. Maternal age, year of delivery (period), and maternal year of birth (birth cohort), as well as race, were examined as risk factors for chronic hypertension. Prevalence rates and rate ratios with 95% CIs of chronic hypertension in relation to age, period, and birth cohort were derived through age-period-cohort models. We also examined how changes in obesity and smoking rates influenced age-period-cohort effects. The overall prevalence of chronic hypertension was 0.63%, with black women (1.24%) having more than a 2-fold higher rate than white women (0.53%; rate ratio, 2.31; 95% CI, 2.30-2.32). In the age-period-cohort analysis, the rate of chronic hypertension increased sharply with advancing age and period from 0.11% in 1970 to 1.52% in 2010 (rate ratio, 13.41; 95% CI, 13.22-13.61). The rate of hypertension increased, on average, by 6% (95% CI, 5-6) per year, with the increase being slightly higher among white (7%; 95% CI, 6%-7%) than black (4%; 95% CI, 3%-4%) women. Adjustments for changes in rates of obesity and smoking were not associated with age and period effects. We observed a substantial increase in chronic hypertension rates by age and period and an over 2-fold race disparity in chronic hypertension rates.

A Case of Progressive Diabetic Retinopathy Related to Pregnancy Followed on Optical Coherence Tomography Angiography.

A 27-year-old woman with type 2 diabetes mellitus had mild diabetic retinopathy (DR) during the early gestation period. Optical coherence tomography angiography (OCTA) showed microaneurysms and small capillary nonperfusion with little change until before delivery. The patient later developed pregnancy-induced hypertension, which continued after delivery, and the DR worsened markedly. OCTA showed onset and recovery of paracentral acute middle maculopathy. Macular edema (ME) also developed, and OCTA showed irregular dilation in the radial peripapillary capillaries. After starting antihypertensive therapy, the capillary dilation and ME decreased. OCTA enables close follow-up of DR related to pregnancy during the perinatal period. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:393-397.].

Efectos de la aspirina en fetos de rata con reducción de la presión de la perfusión uterina / Effects of aspirin on rat fetuses with reduction of uterine perfusion pressure

La preeclampsia (PE) es un trastorno hipertensivo inducido por el embarazo donde se reduce la presión de la perfusión uterina. Investigaciones avalan el uso de dosis baja de aspirina (DBAAS) y su utilidad en la prevención de PE en gestantes con factores de riesgo. Sus beneficios en modelos animales sometidos a esta reduccción no están determinados. El objetivo de la investigación fue analizar la presión arterial sistémica y los hallazgos morfológicos a nivel renal en fetos de ratas con reducción de la presión de perfusión uterina (RPPU) expuestas a DBAAS en comparación a las no expuestas. Se conformaron cuatro grupos de ratas hembras preñadas Sprague Dawley (n=5). A los 14,5 días post-concepción (dpc), vía quirúrgica se indujo RPPU, ligando arterias uterinas, conformándose el grupo RPPU y el grupo RPPU+DBAAS al que se le administró 5 mg/kg/día de aspirina vía oral. El grupo control lo conformaron las no operadas y el grupo DBAAS se le administró aspirina en igual dosis desde el 14,5 dpc. A los 18,5 dpc, previo a la eutansia se midió la presión arterial sistémica con pletismógrafo caudal Insight v2.11 y se extrajeron los fetos. Se midió la longitud céfalo-caudal (LCC), se procesaron y tiñeron con hematoxilina-eosina, describiéndose cortes histológicos transversales a nivel renal. Se determinó que en la presión arterial media, hubo diferencias significativas entre el grupo RPPU y RPPU+DBAAS (p<0,05). El tamaño de los fetos fue menor en el grupo RPPU (p<0,0001), donde 1 feto presentó hernia umbilical congénita. La cuantificación de vesículas renales también fue menor (p<0,005). En conclusión, la administración de DBAAS disminuye los efectos inducidos por la RPPU en cuanto al tamaño fetal, morfología renal y malformaciones congénitas como hernia umbilical. En cuanto a la presión arterial sistémica, tendría efectos sólo en presión arterial media.

Preeclampsia (PE) is a hypertensive disorder induced by pregnancy where there is a reduction in the uterine perfusion pressure. Research supports the use of low dose aspirin (LDAAS) and its usefulness in the prevention of PE in pregnant women with risk factors. Their benefits in animal models subject to RUPP are not determined. The objective of the investigation was to analyze the systemic blood pressure and the morphological findings at renal level in fetuses of rats with reduction of uterine perfusion pressure (RUPP) exposed to LDAAS compared to those not exposed. Four groups of pregnant female rats Sprague Dawley (n=5) were formed. At 14.5 days post-conception (dpc), surgical RUPP was induced, ligating uterine arteries, with the RUPP group and RUPP+LDAAS group being given 5 mg/kg/day of aspirin orally. The control group was made up of those not operated and the LDAAS group was administered aspirin in the same dose from 14.5 dpc. A 18.5 dpc, prior to euthanasia systemic blood pressure was measured with flow plethysmograph Insight v2.11 and fetuses were extracted. The cephalo-caudal length (CCL) was measured, processed and stained with hematoxylin-eosin, describing transverse histological sections at the kidney level. It was determined that in the mean arterial pressure, there were significant differences between the group RUPP and RUPP+LDAAS (p <0.05). The size of the fetuses was lower in the RUPP group (p <0.0001), where one fetus presented congenital umbilical hernia. The quantification of renal vesicles was also lower (p <0.005). In conclusion, the administration of LDAAS decreases the effects induced by RUPP in terms of fetal size, renal morphology and congenital malformations such as umbilical hernia. Regarding the systemic blood pressure, effects would only mean arterial pressure.

Effect of Magnesium Sulfate Combined with Phentolamine and Nifedipine for Gestational Hypertension and Serum Levels of LIF and Apelin.

OBJECTIVE: To investigate the effect of magnesium sulfate combined with phentolamine and nifedipine for the treatment of gestational hypertension and on the levels of serum LIF and Apelin. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Obstetrics and Gynecology Clinics, The Affiliated Hospital North China University of Science and Technology, China, from September 2016 to February 2018. METHODOLOGY: One hundred and sixty patients with gestational hypertension were randomly divided into a control group and an observation group, 80 patients in each group. Control group was given magnesium sulfate alone, while observation group was added with phentolamine and nifedipine on the basis of the treatment in control group. Curative effects, pregnancy outcomes, and levels of serum LIF and Apelin were compared. RESULTS: The total effective rate of treatment in the observation group was higher than that in the control group (p=0.005). After treatment, level of serum LIF in the observation group was higher than that in the control group (p<0.001), and level of serum Apelin in the observation group was lower than that in the control group (p<0.001). Incidence of premature birth, cesarean section and neonatal asphyxia in the observation group were all lower than those in the control group (p=0.005, p<0.001 and p=0.005, respectively), while there was no significant difference in the incidence of neonatal death between the two groups (p=0.316). CONCLUSION: Magnesium sulfate combined with phentolamine and nifedipine has a better therapeutic effect on gestational hypertension, which can effectively regulate the levels of serum LIF and Apelin and improve pregnancy outcomes.

Multivariable evaluation of maternal hemodynamic profile in pregnancy complicated by fetal growth restriction: prospective study.

OBJECTIVE: To evaluate the association between fetal growth restriction (FGR) and maternal hemodynamic parameters using multivariable analysis, adjusting for major confounding factors, such as hypertensive disorders of pregnancy (pre-eclampsia and gestational hypertension). METHODS: A prospective cohort study was conducted between January 2013 and April 2016. Two cohorts of patients were recruited, between 24 and 39 weeks of gestation, in a high-risk outpatient setting. These cohorts comprised 49 appropriate-for-gestational-age singleton fetuses and 93 that were FGR (abdominal circumference (AC) at recruitment in the second half of pregnancy ≤ 10th percentile with a previous normal AC at 20-22 weeks). Maternal echocardiography was performed at the time of enrolment and included hemodynamic parameters of systolic and diastolic function and cardiac remodeling indices. Data were analyzed using a multivariable generalized linear model to estimate the association of FGR with maternal hemodynamic parameters after adjusting for significant confounding factors. RESULTS: In the multivariable analysis, after adjustment for hypertensive disorders of pregnancy and smoking, FGR was associated with a 14% increase in maternal total vascular resistance, 16% reduction in cardiac output, 13% reduction in left ventricular mass and 11% reduction in heart rate; similar results were observed for the corresponding indexed parameters. Hypertensive disorders of pregnancy in the absence of FGR were associated with a 25% increase in total vascular resistance, 16% increase in left ventricular mass and 14% reduction in diastolic function; similar results were observed for the corresponding indexed parameters. CONCLUSION: FGR is significantly and independently associated with several maternal hemodynamic parameters, even after adjustment for major confounding factors, such as hypertensive disorders of pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Angiogenic Dysregulation in Pregnancy-Related Hypertension-A Role for Metformin.

In the face of escalating maternal and fetal health threats, hypertensive pregnancy disorders (HPDs) is one of the leading cause of maternal and fetal morbidity and mortality. The range of HPDs include white-coat hypertension, chronic hypertension, gestational hypertension, mild-to-moderate and severe preeclampsia and eclampsia. Current evidence implicates an imbalance of circulating anti- and angiogenic factors in HPDs emanating from the placental vasculature, impacting on angiogenesis. Delivery of the fetus is thus far the only curative measure, albeit with increased risk. Resultant endothelial dysfunction caused by the excessive production of placental soluble fms-like tyrosine kinase-1 has been the basis of many studies to find a safer treatment strategy. Metformin, used historically in the treatment of diabetes mellitus has also found its therapeutic reach in many other disease states. These include, but are not limited to, improving blood flow in certain cancer types, treatment of polycystic ovarian disease, improving vasodilation, and reducing inflammation. Metformin is used to treat hyperglycemic endothelial dysfunction through the enhancement of the nitric oxide system, endothelin-derived hyperpolarizing factor and sirtuin 1. Similarly, endothelial dysfunction in preeclampsia and other HPDs leads to a hypoxic state and elevated blood pressures. Dubbed as the new "aspirin" of current times, the retardation of the antiangiogenic status by metformin provides an exciting and promising alternate strategy in treating these pregnancy disorders.

Therapeutic Effect of Long-Term Epidural Block in Rats with Pregnancy Induced Hypertension.

BACKGROUND: Pregnancy induced hypertension (PIH) causes a variety of systemic disorders that negatively affect the maternal placenta and fetal growth. Epidural sympathetic block elicits symptoms of decreased blood pressure. This study was designed to determine the therapeutic effect of long-term epidural block in rats with PIH. METHODS: Forty healthy pregnant Sprague Dawley rats were randomized into four groups with each group consisting of 10 rats. On gestation day (GD) 14, rats in control group underwent a sham procedure; rats in RUPP group were operated on to obtain reduced uterine perfusion pressure (RUPP); rats in RUPP plus normal saline (NS) group were also subjected to the RUPP procedure and underwent epidural block with 25 µl normal saline twice daily until delivery; rats in RUPP plus epidural block (EB) group were treated as those in RUPP plus NS group except that an epidural block with 25 µl of 0.125% bupivacaine was administered two times per day until delivery. On GD 20, blood pressure was measured in all groups before delivery, and blood samples were collected in order to quantify the serum concentrations of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1). RESULTS: The mean arterial pressure (MAP) of rats in RUPP group (147.6 ± 6.0 mmHg) was markedly increased when compared with control group (80.8 ± 4.6 mmHg) (p < 0.05). The MAP of rats in RUPP plus EB group (114.4 ± 7.2 mmHg) was clearly decreased in contrast with RUPP group but was still higher than in control group (p < 0.05). The variation of fetal weight in all groups followed a similar trend to that of MAP. However, there were no significant differences between control group and RUPP plus EB group with respect to placental weight (p = 0.186). Variation in MAP was positively correlated with the expression of sFlt-1 in each group but was negatively correlated with VEGF. CONCLUSION: This study demonstrates that long-term epidural block decreases blood pressure in PIH rats and improves the serum concentrations of VEGF and sFlt-1. Taken together, long-term epidural block may have a potential role in PIH treatment.

Takayasu arteritis a cause of hypertensive disorder of pregnancy: a case report.

BACKGROUND: Takayasu arteritis is a rare, chronic, granulomatous systemic vasculitis of unknown etiology and a few cases have been reported in pregnancy. In pregnancies concomitant with Takayasu arteritis or after diagnosis, Takayasu arteritis negatively affects pregnancy by increasing 13-fold the odds of complications such as hypertensive disorders. The best recommendations in this scenario are still to be made. CASE PRESENTATION: We present a case of 21-year-old, gravid 1, Mexican woman of Mestizo descent with chronic hypertension diagnosed since she was 15-years old who presented severe hypertension during pregnancy (early second trimester); the diagnosis of hypertensive disorder of pregnancy was ruled out requiring first-line and second-line antihypertensive therapy without serious associated maternal or fetal morbidity. CONCLUSIONS: Takayasu arteritis and pregnancy play an important role in maternal and fetal outcomes. Efforts should be made to further investigate the Takayasu arteritis diagnosis in pregnant women with refractory hypertension.

Prescripción de metildopa en el tratamiento de pacientes con enfermedad hipertensiva en el embarazo / Methyldopa prescription in patients with hipertensive disease during pregnancy

Se realizó un estudio descriptivo y transversal, de utilización de medicamentos, de tipo indicación-prescripción, de 67 gestantes con enfermedad hipertensiva en el embarazo, atendidas en el Hospital Materno Sur Mariana Grajales Coello de Santiago de Cuba, desde julio de 2015 hasta junio de 2016, con vistas a caracterizar la prescripción de metildopa en estas pacientes. En la casuística predominó el uso de este fármaco en las pacientes que tenían situaciones asociadas con las formas más graves de la enfermedad, tales como la edad avanzada, la nuliparidad y el antecedente de hipertensión arterial. Las principales dificultades correspondieron a la combinación de medicamentos con riesgo de interacciones con la metildopa y al empleo de esta a dosis elevadas

A descriptive cross-sectional indication-prescription study of medications use, of 67 pregnant women with hipertensive disease during pregnancy, assisted in Mariana Grajales Coello Southern Maternal Hospital was carried out in Santiago de Cuba, from July, 2015 to June, 2016, aimed at characterizing methyldopa prescription in these patients. The use of this medicine prevailed in the case material in patients that had situations associated with the most serious forms of the disease, such as advanced age, nonpariity and hypertension history. The main difficulties corresponded to the combination of medicines with risk of methyldopa interactions and its use at a high dose