Novel Cardiovascular Biomarkers Associated with Increased Cardiovascular Risk in Women With Prior Preeclampsia/HELLP Syndrome: A Narrative Review
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ABSTRACT:
SUBMITTER: Bovee E
PROVIDER: S-EPMC8546910 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Preeclampsia (PE) constitutes one of the principal reasons for maternal and perinatal morbidity and mortality worldwide. The circumstance typically implicates formerly healthful normotensive women, after 20 weeks of gestation, typically withinside the third trimester, without regarded threat elements or past deliveries. PE can be further complicated with hemolysis and thrombocytopenia, leading to the emergence of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low platelets). Both conditions are classified as hypertensive diseases of pregnancy (HDP), and their pathogenesis has been linked to an excessive maternal inflammatory response, accompanied by enhanced endothelial activation. Several studies have found that in pregnancies affected by PE/HELLP, von Willebrand factor (vWF) antigen levels (vWF:Ag) are significantly elevated, while its cleaving protease (ADAMTS-13, A Disintegrin-like and Metalloprotease with Thrombospondin type 1 motif, member 13) activity is normal to decreased. Furthermore, the higher urine excretion of the terminal complement complex C5b-9, as well as its greater deposition in the placental surface in preeclamptic women, imply that the utero-placental unit's distinctive deficits are intimately tied to disproportionate complement activation. The goal of this updated evaluation is to provide the most up-to-date molecular advances in the pathophysiology of PE/HELLP syndromes. Recent medical data on vWF:Ag levels in patients with PE, ADAMTS-13, and dysregulation of the complement system, are highlighted and evaluated. Furthermore, we discuss the relationship between those entities and the progression of the disease, as well as their significance in the diagnostic process. Finally, considering the difficulties in analyzing and controlling those symptoms in pregnant women, we can provide a current diagnostic and therapeutic algorithm.
| S-EPMC8999044 | biostudies-literature
Project description:Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the -670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.
| S-EPMC4060423 | biostudies-literature
Project description:BACKGROUND:Cardiovascular disease (CVD) is the leading cause of death in women in every major developed country and in most emerging nations. Complications of pregnancy, including preeclampsia, indicate a subsequent increase in cardiovascular risk. There may be a primary care provider knowledge gap regarding preeclampsia as a risk factor for CVD. The objective of our study is to determine how often internists at an academic institution inquire about a history of preeclampsia, as compared to a history of smoking, hypertension and diabetes, when assessing CVD risk factors at well-woman visits. Additional aims were (1) to educate internal medicine primary care providers on the significance of preeclampsia as a risk factor for CVD disease and (2) to assess the impact of education interventions on obstetric history documentation and screening for CVD in women with prior preeclampsia. METHODS:A retrospective chart review was performed to identify women ages 18-48 with at least one prior obstetric delivery. We evaluated the frequency of documentation of preeclampsia compared to traditional risk factors for CVD (smoking, diabetes, and chronic hypertension) by reviewing the well-woman visit notes, past medical history, obstetric history, and the problem list in the electronic medical record. For intervention, educational teaching sessions (presentation with Q&A session) and education slide presentations were given to internal medicine physicians at clinic sites. Changes in documentation were evaluated post-intervention. RESULTS:When assessment of relevant pregnancy history was obtained, 23.6% of women were asked about a history preeclampsia while 98.9% were asked about diabetes or smoking and 100% were asked about chronic hypertension (p?<?0.001). Education interventions did not significantly change rates of screening documentation (p?=?0.36). CONCLUSION:Our study adds to the growing body of literature that women with a history of preeclampsia might not be identified as having increased CVD risk in the outpatient primary care setting. Novel educational programming may be required to increase provider documentation of preeclampsia history in screening.
| S-EPMC7528479 | biostudies-literature
Project description:PurposeHypertensive disorders of pregnancy are still a leading cause of maternal and neonatal morbidity and mortality worldwide. Women with a history of preeclampsia have an increased risk for future cardiovascular and cerebrovascular disease, renal disease as well as diabetes mellitus. There is little knowledge on postpartum risk management. The aim of this study was to assess follow-up care for patients after pre-eclampsia or HELLP syndrome.MethodsThis questionnaire-based cross-sectional study aimed to evaluate the current recommendations of obstetricians in Austria regarding follow-up care, long-term risk counselling and risk of recurrence in future pregnancies after preeclampsia or HELLP syndrome. Data were collected using a survey, based on recommendations given by three substantial guidelines on hypertensive disorders of pregnancy, which was distributed via e-mail to 69 public obstetric departments in Austria. Each obstetric department was required to answer one questionnaire per local protocol.ResultsOur results revealed that of the 48 participating hospitals most obstetricians are aware of the importance of follow-up care for women after a pregnancy complicated by preeclampsia. Our data show that most physicians counselled patients about the future cardiovascular health risks associated with preeclampsia or HELLP syndrome (79.2%). Most obstetricians recommended lifestyle modification (77.1%) and continued blood pressure measurements (97.9%). All centers stated to counsel about the risk of recurrence (100%). However, counselling regarding follow-up care to exclude kidney damage (37.5%) and underlying diseases like thrombophilia (39.6%) were less prioritized.ConclusionsWe were able to show that counselling concerning the risk of long-term cardiovascular disease and risk of recurrence after a pregnancy complicated by preeclampsia or HELLP syndrome has been established in obstetric departments in public hospitals. Regarding the evaluation of underlying chronic diseases such as thrombophilia or renal disease, as well as counselling on the future risk of renal disease is still improvable according to our data. Further evaluation of follow-up care after hypertensive disorders of pregnancy in the outpatient and private sector and implementation of structured guidelines for follow-up, as well as screening for cardiovascular disease are necessary to ensure adequate risk management and to provide opportunities for prevention.
| S-EPMC8918160 | biostudies-literature
Project description:Preeclampsia is characterized by maternal systemic anti-angiogenic and pro-inflammatory states. Syndecan-1 is a cell surface proteoglycan expressed by the syncytiotrophoblast, which plays an important role in angiogenesis and resolution of inflammation. Our aim was to examine placental syndecan-1 expression in preeclampsia with or without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Placentas were obtained from women in the following groups: (1) late-onset preeclampsia (n = 8); (2) early-onset preeclampsia without (n = 7) and (3) with HELLP syndrome (n = 8); (4) preterm controls (n = 5); and (5) term controls (n = 9). Tissue microarrays (TMAs) were constructed from paraffin-embedded placentas. TMA slides were immunostained for syndecan-1 and evaluated using microscopy, virtual microscopy, and semi-automated image analysis. Maternal sera from patients with preeclampsia (n = 49) and controls (n = 32) were immunoassayed for syndecan-1. BeWo cells were treated with Forskolin or Latrunculin B or kept in ischemic conditions. SDC1 expression and syndecan-1 production were investigated with qRT-PCR, confocal microscopy, and immunoassays. Syndecan-1 was localized to the syncytiotrophoblast apical membrane in normal placentas. Syndecan-1 immunoscores were higher in late-onset preeclampsia (p = 0.0001) and early-onset preeclampsia with or without HELLP syndrome (p = 0.02 for both) than in controls. Maternal serum syndecan-1 concentration was lower in preeclampsia (median, 673 ng/ml; interquartile range, 459-1,161 ng/ml) than in controls (1,158 ng/ml; 622-1,480 ng/ml). SDC1 expression and syndecan-1 immunostainings in BeWo cells and syndecan-1 concentrations in supernatants increased during cell differentiation. Disruption of the actin cytoskeleton with Latrunculin B decreased syndecan-1 release, while ischemic conditions increased it. Syncytiotrophoblastic syndecan-1 expression depends on the differentiation of villous trophoblasts, and trophoblastic syndecan-1 release is decreased in preeclampsia and HELLP syndrome. This phenomenon may be related to the disturbed syncytiotrophoblastic cortical actin cytoskeleton and associated with maternal anti-angiogenic and pro-inflammatory states in these syndromes.
| S-EPMC3939785 | biostudies-literature
Project description:BackgroundWomen with prior severe preeclampsia are at an increased risk for cardiovascular diseases later in life compared to women who had a normotensive pregnancy. The objective of this study was to assess their needs and preferences regarding app-based cardiovascular health promotion.MethodsPatients (n = 35) of the Follow-Up PreEClampsia Outpatient Clinic (FUPEC), Erasmus MC, the Netherlands, participated in an anonymous online survey. The main outcomes under study were women's needs for health behavior promotion, and their preferences with respect to intervention delivery. Descriptive statistics were used to evaluate needs, and thematic analysis was used to analyze preferences.ResultsWomen's primary need for health behavior promotion pertained to their fat and sugar intake and physical activity; for some, to their mental health (practices), fruit and vegetable intake, salt intake, and water intake; and for a few, to their alcohol and tobacco use. Most women preferred an app-based intervention to include, in descending order: the tracking of health-related metrics, an interactive platform, the use of behavior change strategies, the provision of information, and personalization.ConclusionCardiovascular health promotion targeting women with prior severe preeclampsia should feel relevant to its audience. App-based interventions are likely to be well received if they target fat and sugar intake and physical activity. These interventions should preferably track health-related metrics, be interactive, contain behavior change strategies, provide information, and be personalized. Adopting these findings during intervention design could potentially increase uptake, behavior change, and behavior change maintenance in this population.
| S-EPMC9618195 | biostudies-literature
Project description:BACKGROUND:The involvement of the placenta in the pathogenesis of preeclampsia and HELLP syndrome is well established, and placental lesions are also similar in these two syndromes. Here we aimed to examine the placental transcriptome and to identify candidate biomarkers in early-onset preeclampsia and HELLP syndrome. METHODS:Placental specimens were obtained at C-sections from women with early-onset preeclampsia and HELLP syndrome, and from controls who delivered preterm or at term. After histopathological examination, fresh-frozen placental specimens were used for microarray profiling and validation by qRT-PCR. Differential expression was analysed using log-linear models while adjusting for gestational age. Gene ontology and pathway analyses were used to interpret gene expression changes. Tissue microarrays were constructed from paraffin-embedded placental specimens and immunostained. RESULTS:Placental gene expression was gestational age-dependent among preterm and term controls. Out of the 350 differentially expressed genes in preeclampsia and 554 genes in HELLP syndrome, 224 genes (including LEP, CGB, LHB, INHA, SIGLEC6, PAPPA2, TREM1, and FLT1) changed in the same direction (elevated or reduced) in both syndromes. Many of these encode proteins that have been implicated as biomarkers for preeclampsia. Enrichment analyses revealed similar biological processes, cellular compartments and biological pathways enriched in early-onset preeclampsia and HELLP syndrome; however, some processes and pathways (e.g., cytokine-cytokine receptor interaction) were over-represented only in HELLP syndrome. CONCLUSION:High-throughput transcriptional and tissue microarray expression profiling revealed that placental transcriptomes of early-onset preeclampsia and HELLP syndrome largely overlap, underlying a potential common cause and pathophysiologic processes in these syndromes. However, gene expression changes may also suggest a more severe placental pathology and pronounced inflammatory response in HELLP syndrome than in preeclampsia.
| S-EPMC3917714 | biostudies-literature
Project description:Preterm preeclampsia is associated with the failure of trophoblast invasion, placental hypoxic/ischemic injury and the release of toxic substances, which promote the terminal pathway of preeclampsia. In term preeclampsia, factors yet unknown trigger the placenta to induce the terminal pathway. The contribution of the villous trophoblast to these pathologic events has not been fully elucidated. Here we aimed to study how stress and signaling pathways influence trophoblastic functions in various subforms of preeclampsia. Tissue microarrays (TMAs) were constructed from placentas obtained from pregnant women in the following groups: 1-2) preterm preeclampsia with (n?=?8) or without (n?=?7) HELLP syndrome; 3) late-onset preeclampsia (n?=?8); 4-5) preterm (n?=?5) and term (n?=?9) controls. TMA slides were stained for phosphorylated Akt-1, ERK1/2, JNK, and p38 kinases, and trophoblastic immunostainings were semi-quantitatively evaluated. BeWo cells were kept in various stress conditions, and the expression of FLT1, GCM1, LEP, and PGF was profiled by qRT-PCR, while Akt-1, ERK1/2, JNK, and p38 kinase activities were measured with phospho-kinase immunoassays. We found that: 1) Placental LEP and FLT1 expression was up-regulated in preterm preeclampsia with or without HELLP syndrome compared to controls; 2) Mean pp38 immunoscore was higher in preterm preeclampsia, especially in cases with HELLP syndrome, than in controls. 3) Mean pERK1/2 immunoscore was higher in preterm preeclampsia with HELLP syndrome than in controls. 4) In BeWo cells, ischemia up-regulated LEP expression, and it increased JNK and decreased ERK1/2 activity. 5) Hypoxia up-regulated FLT1 and down-regulated PGF expression, and it increased ERK1/2, JNK and p38 activity. 6) IL-1? treatment down-regulated PGF expression, and it increased JNK and p38 activity. 7) The p38 signaling pathway had the most impact on LEP, FLT1 and PGF expression. In conclusion, hypoxic and ischemic stress, along with unknown factors, activates trophoblastic p38 signaling, which has a key role in villous trophoblastic functional changes in preterm preeclampsia. The activation of ERK1/2 signaling may induce additional trophoblastic functional changes in HELLP syndrome, while distinct mechanisms may promote late-onset preeclampsia.
| S-EPMC5987200 | biostudies-literature
Project description:ProblemCytomegalovirus (CMV) infection was previously reported in pregnancy complications. However, its seroprevalence and associated Toll-like receptor (TLR) expression in early-onset preeclampsia (EOPE) with hemolysis, elevated liver enzyme and low platelets syndrome (HELLPs) are unexplored.Method of studyA case–control study was performed to examine maternal CMV antibodies, neutrophil Toll-like receptor (TLR)-2 and -4 expression as well as the cytokine profile in EOPE with HELLPs (EOPE-HELLPs) (n = 10), late-onset preeclampsia (LOPE) (n = 20), normal pregnancy (n = 60), and non-pregnancy (n = 20) controls.ResultsEOPE-HELLPs had significantly increased CMV IgG sero-positivity, upregulated TLR-2/-4 mRNA expression, increased serum IL-6 and TNF-α, and reduced IL-10 compared with matched normal and non-pregnancy controls. No significant difference was observed between LOPE and normal pregnancy controls.ConclusionWe observed a significant association between CMV IgG sero-positivity and innate immune response in EOPE-HELLPs. Our data suggest that CMV infection may be a risk factor for this disorder.
| S-EPMC3999254 | biostudies-literature
Project description:During pregnancy, substantial alterations in cerebral plasticity, vascular remodeling and neuronal growth occur in the maternal brain. We investigated whether concentrations of selected neurodiagnostic biomarkers in the cerebrospinal fluid of women with preeclampsia/HELLP syndrome differ from those in healthy controls using enzyme-linked immunosorbent assay technique. We found that tau protein concentrations (p = 0.016) and phospho-tau/tau ratio (p < 0.001) in cerebrospinal fluid were significantly lower in 39 preeclamptic women compared to 44 healthy controls during third trimester of pregnancy. Beta-amyloid(1-40)/(1-42) ratio was significantly higher in HELLP syndrome than in severe preeclampsia (8.49 + 2.73 vs. 4.71 + 1.65; p = 0.007). We conclude that beta-amyloid(1-40)/(1-42) ratio in cerebrospinal fluid can discriminate severe preeclampsia and HELLP syndrome. High beta-amyloid peptide and low tau protein concentrations are associated with impaired development of the materno-feto-placental unit and correlate with placental dysfunction.
| S-EPMC7113242 | biostudies-literature