Severe Hypertensive Disorders Research Articles

Can Peripheral Arterial Tonometry and Biomarkers Help Identify Women Who Will Have Progressively Worsening Hypertensive Disorders of Pregnancy?

This study aimed to (1) evaluate whether endothelial dysfunction, as measured by peripheral arterial tonometry (PAT) indices and biomarker (soluble fms-like tyrosine kinase-1 [sFLT], brain natriuretic peptide [BNP]) levels at 34 weeks gestation, can predict progression from nonsevere to severe hypertensive disorders of pregnancy (HDPs); and (2) develop a clinical risk model for prediction of progression from nonsevere to severe HDP. We prospectively enrolled patients with a singleton gestation carrying a nonsevere HDP diagnosis. Forty-five participants were enrolled for PAT evaluation and serum collection between 340/7 and 366/7 weeks. PAT indices (e.g., Augmentation Index normalized to a heart rate of 75 bpm [AI75]) and biomarker concentrations were assessed at enrollment. The primary outcome was progression from a nonsevere diagnosis in the late preterm period to a diagnosis of preeclampsia with severe features or superimposed preeclampsia. Statistical analyses included two-sample t-tests, Fisher's exact tests, and multivariate modeling. Thirteen subjects (30%) progressed to severe disease. No significant differences in mean PAT indices between the outcome groups were found. We found a significant difference in mean sFLT values between the two groups (p = 0.02, area under the curve [AUC] of 0.609), but not in mean BNP values. An endothelial dysfunction index (presence of fetal growth restriction, "high" AI75, and positive systolic blood pressure slope) discriminated between progression and nonprogression (p = 0.03, AUC of 0.707). sFLT level was a marker of progression from nonsevere to severe HDP. Further, a novel endothelial dysfunction index discriminated between progression and nonprogression to severe disease with good performance. · HDPs are important causes of morbidity and mortality.. · The sequelae of HDPs are not limited to pregnancy.. · Developing accurate tools to predict severe HDPs is of great clinical importance.. · Our index shows promising performance for predicting progression from nonsevere to severe HDPs..

Moving the needle: Quality improvement strategies to achieve guideline-concordant care of obstetric patients with severe hypertension

ObjectivesTo improve timely treatment and follow-up of birthing individuals with severe hypertension. Study designA quality improvement (QI) initiative was implemented at an academic tertiary care center in the United States of America for individuals with obstetric hypertensive emergencies. Statistical process control charts were utilized to track process measures and interventions tested through plan-do-study-act cycles. Measures were disaggregated by race and ethnicity to identify and improve disparities. Main outcome measuresTreatment of hypertensive events within 60 min, receipt of blood pressure (BP) device at discharge and completed postpartum follow-up BP check within 7 days of discharge. ResultsAll process measures showed statistically significant improvements. The primary process measure, timely treatment of hypertensive emergencies, improved from 29 % to 76 %. Receipt of BP device improved from 37 % to 91 % and follow-up BP checks from 58 % to 81 %. No racial or ethnic disparities were noted at baseline or after interventions. Readmission rates within 6 weeks of delivery increased from 2.3 % to 6.1 % for the cohort with no severe morbidity or mortality events after discharge. Strategies associated with improvement included project launch with establishment of the “why,” telehealth, simulation, a video display of quality metrics on the birthing unit, promoting BP cuff access, and automated orders. ConclusionsThis comprehensive QI initiative provides novel improvement strategies for the management of individuals with severe hypertensive disorders of pregnancy for the timely treatment of severe BP, attainment of home BP devices, and follow-up after discharge. Quality improvement methodology is practical and essential for achieving guideline-concordant care.

Differential proteomics of circulating extracellular vesicles of placental origin isolated from women with early-onset preeclampsia reveal aberrant innate immune and hemostasis processes.

Early-onset preeclampsia (EOPE) is a severe gestational hypertensive disorder with significant feto-maternal morbidity and mortality due to uteroplacental insufficiency. Circulating extracellular vesicles of placental origin (EV-P) are known to be involved in the pathophysiology of EOPE and might serve as an ideal reservoir for its specific biomarkers. Therefore, we aimed to characterize and perform comparative proteomics of circulating EV-P from healthy pregnant and EOPE women before delivery. The EV-P from both groups were isolated using immunoaffinity and were characterized using transmission electron microscopy, dynamic light scattering, nanoparticle tracking analysis, and immunoblotting. Following IgG albumin depletion, the pooled proteins that were isolated from EV-P of both groups were subjected to quantitative TMT proteomics. Circulating term EV-P isolated from both groups revealed ∼150nm spherical vesicles containing CD9 and CD63 along with placental PLAP and HLA-G proteins. Additionally, the concentration of EOPE-derived EV-P was significantly increased. A total of 208 proteins were identified, with 26 among them being differentially abundant in EV-P of EOPE women. This study linked the pathophysiology of EOPE to 19 known and seven novel proteins associated with innate immune responses such as complement and TLR signaling along with hemostasis and oxygen homeostasis. The theory suggesting circulating EVs of placental origin could mimic molecular information from the parent organ-"the placenta"-is strengthened by this study. The findings pave the way for possible discovery of novel prognostic and predictive biomarkers as well as provide insight into the mechanisms driving the pathogenesis of EOPE.

USING A MULTI-OMICS LANDSCAPE OF THE MATERNAL-FETAL INTERFACE TO MODEL THE LONGITUDINAL PATHOGENESIS OF EARLY-ONSET PRE-ECLAMPSIA

Objective: Pre-eclampsia (PE) is a syndrome that affects multiple organ systems and is the most severe hypertensive disorder in pregnancy. It frequently leads to preterm delivery, maternal and fetal morbidity and mortality and life-long complications. We currently lack efficient screening tools and early therapies to address PE. Design and method: To identify candidate biomarkers and operative pathways in early onset PE (eoPE, severe PE with onset before week 34), we performed spatio-temporal multi-omics profiling of human eoPE placentae and healthy controls, and validated targets in early gestation in a longitudinal clinical cohort. We used a single-nuclei RNA-sequencing combined with spatial proteo- and transcriptomics and mechanistic in vitro signalling analyses to bridge the gap from late pregnancy disease to early pregnancy pathomechanisms. Results: We discovered a key disruption in villous trophoblast differentiation, which is driven by the increase of transcriptional coactivator p300, that ultimately ends with a senescence-associated secretory phenotype (SASP) of trophoblasts in eoPE. We found a significant increase in the senescence markers in preeclamptic maternal serum in early gestation and late gestation, before the development of clinical symptoms, indicating that the placental syndrome drives systemic maternal syndrome, even before clinical manifestation of eoPE. Conclusions: Our work describes a new disease progression model, starting with dysregulated transition in villous trophoblast differentiation. Our study identifies potential pathophysiology-relevant biomarkers for the early diagnosis of the disease as well as possible targets for interventions, which would be crucial steps toward protecting the mother and child from gestational mortality and morbidity and an increased risk of cardiovascular disease later in life.

Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence

The "great obstetrical syndromes" of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether one or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. To determine how quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent/reversed umbilical artery Doppler indices, hypertensive disorders of pregnancy, and the two conditions combined among subjects with disease severity warranting early preterm delivery. We hypothesize that trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulate that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction, with no additional effect when hypertension is concomitantly present. In this retrospective cohort study, paraffin-embedded placental tissue was obtained from four groups: [1] Severe fetal growth restriction with absent/reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, [2] Severe fetal growth restriction with absent/reversed umbilical artery Doppler indices and no hypertension,[3] Gestational age-matched, appropriately grown pregnancies with hypertensive disease, and [4] Gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed followed by artificial intelligence-driven morphometric analyses. Number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled with linear regression. Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi, 95% CI: [-467, -98], p<0.01), smaller stem villous area (-4.3 mm2, 95% CI: [-7.3, -1.2], p<0.01), and fewer stem villous vessels (-4967 stem villous vessels, 95% CI [-8501, -1433], p<0.01), with no difference in total vascular area. In contrast, placental abnormalities in severe growth restriction were limited to terminal villi, with global decreases in number of villi (-873 terminal villi, 95% CI: [-1501, -246], p<0.01), villous area (-1.5 mm2, 95% CI: [-2.7, -0.4], p<0.01), number of blood vessels (-5165 terminal villous vessels, 95% CI: [-8201, -2128], p<0.01), and vascular area (-0.6 mm2, 95% CI: [-1.1, -0.1], p=0.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent/reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions with the combination of growth restriction and hypertension, suggesting that distinct pathophysiologic pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to result in more severe pathologic consequences. Delineating mechanisms underlying the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Huc-MSC-derived exosomal miR-144 alleviates inflammation in LPS-induced preeclampsia-like pregnant rats via the FosB/Flt-1 pathway

BackgroundPreeclampsia (PE) is a common and severe hypertensive disorder in pregnancy. Mesenchymal stem cell-derived exosomes (Exos-MSC) have been reported to mitigate the progression of inflammatory diseases. The study aimed to explore the effects of human umbilical cord-derived Exos-MSC (huc-Exos-MSC) on PE-like models. MethodsLipopolysaccharide (LPS) was used to construct in vitro and in vivo PE-like models. Exosomes were treated with LPS-induced PE-like cells and rats. ResultsPE-like inflammatory models of pregnant rats and cells were successfully constructed in vivo and in vitro. miR-144 was screened by bioinformatics analysis. Exosomes were successfully extracted. Silencing FosB, overexpressing miR-144 or treating with exosomes extracted from huc-MSC overexpressing miR-144 in (Exos-MSCmiR−144) reversed the LPS-induced decline in HTR-8/SVneo cell viability and migration. In addition, the above groups decreased LPS-induced increases in interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), phosphorylated nuclear factor-kappaB (p–NF–κB)/NF-κB, soluble FMS-like tyrosine kinase 1 (sFlt-1), and Flt-1 levels. Simultaneously, transfection of miR-144 mimics and overexpressing FosB reversed those changes in the miR-144 mimics group. miR-144 might alleviate LPS-induced HTR-8/SVneo cell inflammation by targeting FosB. Injection of Exos-MSCmiR−144 in PE-like pregnant rats reversed LPS-induced increases in FosB expression, systolic and diastolic blood pressure (SBP and DBP), as well as mean arterial pressure (MAP), heart rate, urine albumin/creatine ratio, inflammatory factors, p–NF–κB/NF-κB, and sFlt-1 levels. Furthermore, compared with the model group, the proportion of live births was significantly higher in the model + Exos-MSCmiR−144 group, while the apoptosis rate of fetal rat brain tissue was significantly lower. ConclusionsWe found that huc-Exos-MSC-derived miR-144 alleviated gestational hypertension and inflammation in PE-like pregnant rats by regulating the FosB/Flt-1 pathway. In addition, huc-Exos-MSC-derived miR-144 could partially reverse the LPS-induced adverse pregnancy outcome and brain injury in fetal rats, laying the foundation for developing new treatments for PE.

Роль корекції ендотеліальної дисфункції в комплексній профілактиці гіпертензивних ускладнень вагітності

Purpose - to study the effect of correction of endothelial dysfunction by the introduction of L-arginine in the comprehensive prevention of the development of severe hypertensive disorders in pregnant women. Materials and methods. The division into groups was carried out indiscriminately following the prescribed bath. 27 women reached the 1st group, who, in addition to basic prevention of preeclampsia (small doses of aspirin for 12 days, calcium supplement 1000 mg per dose for 16 years), took Tivortin until conception and p. It's an hour of urgency; up to the 2nd group - 54 women who did not receive basic prevention of preeclampsia. The control group (3) consisted of 16 healthy women with physiological changes in vagusity. Participants of the 1st group, during the hour of stay in the hospital, took L-arginine internally (iv) (4 g) + 2 teaspoons 2 times (4 g) per os per dose 40 minutes before admission, then 3 teaspoons spoons 2 times (6 g per dose). The average intensity of the droplets became 6. The function of the endothelium was evaluated according to the universally recognized non-invasive cuff test method, which is based on the principle of ultrasound assessment of the change in the diameter of the brachial artery in response to the restoration of blood flow in it after short-term compression of the upper limb with a cuff. Physical condition and endurance were assessed using the generally accepted 6-minute walk method. The quality of life in pregnant women who had experienced severe preeclampsia in the past was assessed in stages - according to the health-related quality of life (HRQoL) scale and the scale created by the World Health Organization (WHOQOL-BREF). Results. Arterial hypertension and preeclampsia are based on changes in endothelium-dependent vasodilatation. A positive effect on the function of the endothelium significantly improves indicators of physical well-being and quality of life. When conducting a test with a 6-minute walk in the Group 1, better indicators were found than in the Group 2 (respectively, 409±23 m vs. 381±32 m, p&lt;0.05), this indicator in the control group was 473±32 m (p&lt;0.05 according to the Groups 1 and 2). However, this indicator significantly improved in pregnant women of the Group 1 after intravenous administration of L-arginine: 441±12 m (p&lt;0.05 compared to the indicator before intravenous administration). According to the assessment of the quality of life of pregnant women of the studied groups, it should be noted that the quality of life indicators in all domains are significantly lower in women of the Group 1, which is associated with significantly worse anamnesis data of such women, significant concern about the results of the next pregnancy. When evaluating indicators of endothelium-dependent and endothelium-independent vasodilatation, it was found that in the group of women who received L-arginine preconceptionally, in the 1st trimester, the indicator before intravenous IV administration was 5.09±0.44, and after - 8.21±0.24, which indicates a significant improvement in endothelium-dependent vasodilation indicators (by 49.1%) 28-32 weeks, there are also no births of children with a body weight of less than 1500 g. Conclusions. In the group of high-risk pregnant women, the use of L-arginine in the complex prevention of preeclampsia allows to reduce the risks of early severe preeclampsia, to reduce the medication burden of two- and three-component hypotensive therapy. An increase in physical endurance, quality of life, and improvement in pregnancy outcomes are due to a positive effect on the function of the endothelium through the optimization of endothelium-dependent vasodilatation associated with the provision of the L-arginine substrate for the full synthesis of nitric oxide. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

CD74 deficiency reduces trophoblast invasion and proliferation mediated by SIRT1 in preeclampsia.

Preeclampsia (PE) is a severe hypertensive disorder during pregnancy, and one of the causes is the dysfunction of extravillous trophoblast cells (EVTs). In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of placentas from PE patients and the sirtuin 1 (SIRT1) heterozygous knockout mouse model, which exhibited typical PE-like symptoms. We identified 134 differentially expressed genes (DEGs) with similar trends in EVTs of PE patients and in parietal trophoblast giant cells (P-TGCs) of Sirt1-/- (HO) placentas from Sirt1+/- (HE) pregnant mice. Interestingly, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 134 overlapping genes were related to the MAPK signaling pathway. We validated several DEGs using immunofluorescence at the protein level. Finally, we selected CD74 for further experiments, which showed a decrease in EVTs of PE patients and in P-TGCs of Sirt1-/- placentas from Sirt1+/- pregnant mice. Additionally, cell proliferation assays and transwell assays showed that the proliferation and invasion abilities were decreased in CD74 knockdown HTR8/SVneo cells using lentivirus transfection, which can be improved by adding the SIRT1 agonist SRT1720 or metformin, an agonist of the MAPK signaling pathway. Importantly, the expression of CD74 can be positively regulated by SIRT1. These data suggest that CD74 plays an important protective role in the pathogenesis of preeclampsia by regulating the MAPK signaling pathway, which can be regulated by SIRT1.

Impact of Aging and Cellular Senescence in the Pathophysiology of Preeclampsia.

The incidence of hypertensive disorders of pregnancy is increasing, which may be due to several factors, including an increased age at pregnancy and more comorbid health conditions during reproductive years. Preeclampsia, the most severe hypertensive disorder of pregnancy, has been associated with an increased risk of future disease, including cardiovascular and kidney diseases. Cellular senescence, the process of cell cycle arrest in response to many physiologic and maladaptive stimuli, may play an important role in the pathogenesis of preeclampsia and provide a mechanistic link to future disease. In this article, we will discuss the pathophysiology of preeclampsia, the many mechanisms of cellular senescence, evidence for the involvement of senescence in the development of preeclampsia, as well as evidence that cellular senescence may link preeclampsia to the risk of future disease. Lastly, we will explore how a better understanding of the role of cellular senescence in preeclampsia may lead to therapeutic trials. © 2023 American Physiological Society. Compr Physiol 13:5077-5114, 2023.

PO2_12. A systematic review about the association among severe maternal morbidity and hypertension disorders

PO2_12. A systematic review about the association among severe maternal morbidity and hypertension disorders

The association between hypertensive disorders during pregnancy and maternal and neonatal outcomes: a retrospective claims analysis

BackgroundHypertensive disorders during pregnancy continue to increase in prevalence and are associated with several adverse outcomes and future cardiovascular risk for mothers. This study evaluated the association of hypertensive disorders compared to no hypertension during pregnancy with neonatal and maternal outcomes. We then evaluated risk factors associated with progression from a less to more severe hypertensive disorder during pregnancy.MethodsWe conducted a propensity-matched retrospective cohort study utilizing Medicaid claims data from a national insurer. The study population consisted of mothers with and without hypertensive disorders who delivered between 7/1/2016–12/31/2018 and their infants. Hypertensive disorders included gestational hypertension, chronic hypertension, preeclampsia, and superimposed preeclampsia. Propensity score matching was used to match mothers without to those with hypertensive disorders. Regression models were used to compare maternal and neonatal outcomes. Stepwise logistic regression was used to determine characteristics associated with the progression of gestational hypertension to preeclampsia or chronic hypertension to superimposed preeclampsia.ResultsWe observed the highest risk of cesarean delivery (odds ratio [OR]:1.61 and 1.99) in mothers and preterm delivery (OR:2.22 and 5.37), respiratory distress syndrome (OR:2.39 and 4.19), and low birthweight (OR:3.64 and 9.61) in babies born to mothers with preeclampsia or superimposed preeclampsia compared to no hypertension, respectively (p < 0.05 for all outcomes). These outcomes were slightly higher among chronic or gestational hypertension compared to no hypertension, however, most were not statistically significant. Risk of neonatal intensive care unit utilization was higher among more severe hypertensive disorders (OR:2.41 for preeclampsia, OR:4.87 for superimposed preeclampsia). Obesity/overweight and having a history of preeclampsia during a prior pregnancy were most likely to predict progression from gestational/chronic hypertension to preeclampsia/superimposed preeclampsia.ConclusionMothers and neonates born to mothers with preeclampsia or superimposed preeclampsia experienced more adverse outcomes compared to those without hypertension. Mothers and neonates born to mothers with gestational hypertension had outcomes similar to those without hypertension. Outcomes for those with chronic hypertension fell in between gestational hypertension and preeclampsia. Obesity/overweight and having a history of preeclampsia during a prior pregnancy were strong risk factors for hypertension progression.

Pregnancy-Induced Hypertensive Disorder and Risks of Future Ischemic and Nonischemic Heart Failure

BackgroundAlthough adverse pregnancy outcomes are associated with an increased risk of cardiovascular disease, studies on timing and subtypes of heart failure after a hypertensive pregnancy are lacking. ObjectivesThe goal of this study was to assess the association between pregnancy-induced hypertensive disorder and risk of heart failure, according to ischemic and nonischemic subtypes, and the impact of disease characteristics and the timing of heart failure risks. MethodsThis was a population-based matched cohort study, comprising all primiparous women without a history of cardiovascular disease included in the Swedish Medical Birth Register between 1988 and 2019. Women with pregnancy-induced hypertensive disorder were matched with women with normotensive pregnancies. Through linkage with health care registers, all women were followed up for incident heart failure, classified as ischemic or nonischemic. ResultsIn total, 79,334 women with pregnancy-induced hypertensive disorder were matched with 396,531 women with normotensive pregnancies. During a median follow-up of 13 years, rates of all heart failure subtypes were more common among women with pregnancy-induced hypertensive disorder. Compared with women with normotensive pregnancies, adjusted HRs (aHRs) with 95% CIs were as follows: heart failure overall, aHR: 1.70 (95% CI: 1.51-1.91); ischemic heart failure, aHR: 2.28 (95% CI: 1.74-2.98); and nonischemic heart failure, aHR: 1.60 (95% CI: 1.40-1.83). Disease characteristics indicating severe hypertensive disorder were associated with higher heart failure rates, and rates were highest within the first years after the hypertensive pregnancy but remained significantly increased thereafter. ConclusionsPregnancy-induced hypertensive disorder is associated with an increased short-term and long-term risk of incident ischemic and nonischemic heart failure. Disease characteristics indicating more severe forms of pregnancy-induced hypertensive disorder amplify the heart failure risks.

Cerebral Small Vessel Disease Subtypes and Blood Pressure Control after Intracerebral Hemorrhage (P7-5.024)

<h3>Objective:</h3> NA <h3>Background:</h3> Intracerebral hemorrhage (ICH) survivors are at high risk of neurological decline for underlying progressive cerebral small vessel disease (CSVD). Most ICHs are attributable to two common CSVD types: cerebral amyloid angiopathy (CAA) and hypertensive-CSVD (HTN-CSVD). HTN-CSVD includes pure deep or mixed location ICH/microbleeds, the latter more severe. Hypertension control being the most potent intervention delaying CSVD-related ICH progression, we investigated whether more severe forms of HTN-CSVD are related to worse blood pressure (BP) control over time after CSVD-related ICH. <h3>Design/Methods:</h3> We analyzed data from consecutive non-traumatic ICH in-patients between 2011–2020 in a tertiary care center. MRI-based CSVD markers classified ICH patients as CAA-related and HTN-CSVD-related, deep and mixed locations within HTN-CSVD. Validated MRI-based score quantified CSVD burden. Longitudinal BP following ICH obtained via semi-automated electronic health records review. Linear mixed effects models examined association of BP during follow-up with CSVD etiology and severity. <h3>Results:</h3> 796 ICH survivors were followed for a median of 48.8 months (interquartile range [IQR] 41.5 – 60.4). CAA-related (n = 373) displayed lower systolic BP (median 138 mmHg, IQR: 133–142 mmHg) compared to deep hypertensive ICH/microbleeds (n = 222, systolic BP median 141 mmHg, IQR: 136–143 mmHg, p = 0.037 for comparison), and mixed location ICH/microbleeds (n = 201, systolic BP median 142 mmHg, IQR: 135–144 mmHg, p = 0.015 for comparison). In multivariable analysis, mixed location ICH/microbleeds (effect: +3.8 mmHg, Standard Error [SE]: 1.3 mmHg, p = 0.008) and increasing CSVD severity (+1.8 mmHg per score point, SE: 0.8 mmHg, p = 0.032) were independently associated with higher follow-up systolic BP. No associations between CSVD subtype/severity and diastolic BP. <h3>Conclusions:</h3> CSVD severity and subtype predict subsequent hypertension control. We confirm previous findings that mixed location ICH/microbleeds are related to more severe hypertensive disorder. Our findings support incorporating MRI-derived CSVD markers when tailoring hypertension control strategies for ICH survivors. <b>Disclosure:</b> Dr. Mallick has nothing to disclose. Dr. Das has nothing to disclose. Ms. Keins has nothing to disclose. Jessica Abramson has nothing to disclose. Juan Pablo Castello, MD has nothing to disclose. Marco Pasi has nothing to disclose. Dr. Popescu has nothing to disclose. Leidys Gutierrez-Martinez has nothing to disclose. Dr. Mayerhofer has nothing to disclose. Christina Kourkoulis has nothing to disclose. Axana Rodriguez-Torres has nothing to disclose. Andrew d. Warren has nothing to disclose. Mrs. Gokcal has nothing to disclose. Dr. Viswanathan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam Pharmaceuticals. Dr. Viswanathan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Viswanathan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharmaceuticals. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Washington University/IQVIA. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Greenberg has received research support from National Institutes of Health. Dr. Greenberg has received publishing royalties from a publication relating to health care. The institution of Dr. Anderson has received research support from Bayer AG. An immediate family member of Dr. Anderson has received publishing royalties from a publication relating to health care. Dr. Rosand has received personal compensation for serving as an employee of Massachusetts General Hospital. Dr. Rosand has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Boehringer Ingelheim. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Rosand has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Boehringer Ingelheim. The institution of Dr. Rosand has received research support from NIH. The institution of Dr. Rosand has received research support from OneMind. The institution of Dr. Rosand has received research support from American Heart Association. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as a Peer reviewer with National Institutes of Health. Dr. Rosand has a non-compensated relationship as a Board Member with Columbia University that is relevant to AAN interests or activities. The institution of Dr. Gurol has received research support from NIH/NINDS. The institution of Dr. Gurol has received research support from Boston Scientific Corporation. The institution of Dr. Gurol has received research support from AVID (a wholly owned subsidiary of Eli Lilly). The institution of Dr. Gurol has received research support from Pfizer. Dr. Biffi has nothing to disclose.

Impact of race/ethnicity on pregnancy outcomes in expectant management of severe hypertensive disorders of pregnancy

Impact of race/ethnicity on pregnancy outcomes in expectant management of severe hypertensive disorders of pregnancy

A randomized trial of the impact of postpartum ibuprofen on severe hypertensive disorders of pregnancy

To evaluate the impact of ibuprofen on postpartum (PP) blood pressure (BP) outcomes in pregnant patients with a new diagnosis of hypertensive disorders of pregnancy (HDP) and antenatal severe hypertension.

Aspirin Inhibits Fibronectin Expression and Reverses Fibronectin-Mediated Cell Invasiveness by Activating Akt Signaling in Preeclampsia.

Preeclampsia is a severe gestational hypertensive disorder that may lead to maternal multiple organ dysfunction and adverse fetal outcomes. Aspirin provides a protective effect by reducing the risk of preeclampsia; however, its mechanism of action is unclear. Fibronectin (FN) is a key factor in cell motility and is associated with preeclampsia. Here, we demonstrated that cellular FN expression was elevated in the placenta of preeclamptic patients. The functional roles of plasma and cellular FN in trophoblasts were investigated by treating HTR-8/SVneo cells with exogenous recombinant human FN protein (rhFN) and siRNA, respectively. Trophoblast migration and invasion were inhibited by rhFN and facilitated by FN knockdown. Moreover, rhFN activated ERK and Akt signaling in trophoblasts, and FN-suppressed cell motility was rescued by ERK and/or Akt inhibitors. In this study, aspirin suppressed trophoblast cellular FN expression and reversed FN-mediated cell functions, including cell migration, invasion, and ERK/Akt signal changes. Taken together, the results of this study revealed the effects of FN on trophoblast motility and signaling; aspirin inhibits FN expression and reverses FN-mediated trophoblast biology. These results provide a drug mechanism for disease prevention and a target for preeclampsia intervention.

D Vitamini Seviyesi Preeklampsinin Şiddetini Değiştirir mi? Tek Merkezli Vaka Kontrol Çalışması

Aim: We aimed to investigate the association between vitamin D deficiency and severity of preeclampsia.&#x0D; Material and Methods: We conducted a case-control study aiming to evaluate vitamin D serum levels in patients with preeclampsia(PE), severe preeclampsia, eclampsia and HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets). Total number of 69 patients between the ages of 18 and 40 either had a spontaneous vaginal delivery or C-section were included in the study. &#x0D; Results: The demographic data of the patients were similar, and age was higher in severe PE than in the other groups. When body mass index (BMI) was evaluated, the average BMI of the patients in the severe PE group was found to be significantly higher than PE and similar to the other groups. The average vitamin D levels of all groups was 8.75±3.5 and the mean of severe PE was 6.69±3, which was significantly lower than the other groups. The average vitamin D level in PE was 10.99±2.91, and it was higher than all groups and was significantly higher than patients with severe PE and HELLP syndrome.&#x0D; Conclusion: We think that there is a significant relationship between the severity of hypertensive disorders that begin during pregnancy and the degree of vitamin D deficiency. We think that the control of vitamin D level and its addition to the treatment will positively affect the course of the disease in order to prevent hypertensive disorders and reduce the severity of disease.

Postpartum Readmission for Hypertension After Discharge on Labetalol or Nifedipine.

To assess whether readmission for hypertension by 6 weeks postpartum differed between patients discharged on nifedipine or labetalol. This cohort study included patients with delivery admissions from 2006 to 2017 who were discharged from the hospital on nifedipine or labetalol and were included in a large, national adjudicated claims database. We identified patients' discharge medication based on filled outpatient prescriptions. We compared rates of hospital readmission for hypertension between patients discharged postpartum on labetalol alone, nifedipine alone, or combined nifedipine and labetalol. Patients with chronic hypertension without superimposed preeclampsia were excluded. Comparisons based on medication were performed using logistic regression models with adjustment for prespecified confounders. Comparisons were also stratified by hypertensive disorder of pregnancy severity. Among 1,582,335 patients overall, 14,112 (0.89%) were discharged postpartum on labetalol, 9,001 (0.57%) on nifedipine, and 1,364 (0.09%) on both medications. Postpartum readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine (641 patients vs 185 patients, 4.5% vs 2.1%, adjusted odds ratio [aOR] 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine for both mild (4.5% vs 2.7%, aOR 1.57, 95% CI 1.29-1.93) and severe hypertensive disorders of pregnancy (261 patients vs 72 patients, 5.7% vs 3.2%, aOR 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent on combined nifedipine and labetalol compared with nifedipine (3.1% vs 2.1%), but the odds were lower after confounder adjustment (aOR 0.80, 95% CI 0.64-0.99). Postpartum discharge on labetalol was associated with increased risk of readmission for hypertension compared with discharge on nifedipine.

Abstract P346: Cardiac Arrest During Delivery Hospitalization And Severe Hypertensive Disorders Of Pregnancy, United States, 2017-2019

Background: Cardiac arrest is a rare and sometimes fatal maternal complication. Severe hypertensive disorders of pregnancy (HDP) including preeclampsia with severe features, eclampsia, and Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome are risk factors for maternal cardiac events. Surveillance on cardiac arrest and severe HDP during delivery is critical to informing evidence-based strategies to reduce pregnancy-related death. Methods: Using pooled data from the National Inpatient Sample from 2017-2019, we identified delivery hospitalizations among women aged 12-55 years. Delivery hospitalizations, cardiac arrest, and maternal medical conditions were identified using ICD-10-CM codes. Survival to hospital discharge was based on patient discharge disposition. Prevalence of cardiac arrest, severe HDP, and survival following cardiac arrest were calculated. We estimated the prevalence of severe HDP among delivery hospitalizations with cardiac arrest, cardiac arrest frequency among delivery hospitalizations with severe HDP, and survival to hospital discharge with co-occurring cardiac arrest and severe HDP. All estimates were weighted to account for complex sampling. Results: During 2017-2019, an estimated 10,921,784 delivery hospitalizations among which 1,465 cardiac arrests were identified. Overall cardiac arrest prevalence was 13.4 per 100,000 delivery hospitalizations (95% CI, 11.9-14.9). Of these, 1,005 (68.6% [95% CI, 63.2-74.0]) survived to hospital discharge. Overall prevalence of severe HDP was 2.7% (95% CI, 2.6-2.7) compared with 15.4% (95% CI 11.2-19.5) of delivery hospitalizations with cardiac arrest. Frequency of cardiac arrest per 100,000 delivery hospitalizations with severe HDP was 76.9 (95% CI, 54.6-99.2). Survival to hospital discharge with co-occurring cardiac arrest and severe HDP was 77.8% (95% CI, 65.6-89.9). Conclusion: Delivery hospitalizations affected by cardiac arrest are rare, and over two thirds survived to hospital discharge. Cardiac arrest disproportionately affected delivery hospitalizations among patients who had severe HDP.

Analysis of treatment for 360 critically ill pregnant and parturient women in intensive care unit

To analyze the clinical characteristics and outcomes of critically ill pregnant and parturient women in intensive care unit (ICU), and to provide clinical experience for the subspecialty construction of critical obstetrics. The clinical data of critically ill pregnant and parturient women admitted to the department of critical care medicine, the Second Affiliated Hospital of Kunming Medical University from January 2011 to December 2019 were collected. The main reasons for maternal transfer to ICU, the causes of maternal death, and organ support measures, etc. were summarized. A total of 39 567 critically ill pregnant and parturient women were admitted to the department of obstetrics in our hospital, and 360 were transferred to ICU, with an average ICU transfer rate of 0.91%. Since 2016, the number of obstetric admissions, the number of ICU transfers and the ICU transfer rate had increased significantly. The average age of severe maternals admitted to ICU was (30.9±5.7) years old. The average acute physiology and chronic health evaluation II (APACHE II) score was 7 (4, 10). The average length of ICU stay was 1 (1, 2) day. The average ventilator duration was 9.0 (3.0, 17.5) hours. The main delivery mode of pregnant women in ICU was cesarean section (84.72%). Forty-eight patients (13.33%) underwent hysterectomy, of which 42 (87.5%) due to postpartum hemorrhage. The top 3 causes of ICU admission were severe postpartum hemorrhage [36.94% (133/360)], hypertensive disorders of pregnancy [21.67% (78/360)], pregnancy with cardiac disease [15.00% (54/360)]. The leading cause of postpartum hemorrhage in women transferred to ICU was placental abnormality [63.98% (103/161)], followed by uterine atony [28.57% (46/161)]. The average blood loss was (4 019±2 327) mL within 24 hours after delivery, and the number of women who underwent hysterectomy due to postpartum hemorrhage decreased year by year. During the study period, there were 2 maternal deaths, which were indirect obstetric deaths, 3 cases were discharged against-advice (expected death), including 1 indirect death and 2 direct obstetric death; the mortality in ICU was 1.39% (5/360). The most common reasons for pregnant and parturient women to be admitted to ICU were severe postpartum hemorrhage and hypertensive disorders of pregnancy. The leading cause of postpartum hemorrhage was placental problem. Indirect obstetric deaths exceeded direct obstetric deaths, mainly due to pregnancy complicated with cardiac disease and severe pneumonia. ICU has become an important battlefield for rescuing critically ill maternal and an important guarantee for reducing the maternal mortality.