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Heart (British Cardiac Society) Apr 2024Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life....
OBJECTIVE
Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life. We investigated whether genetic liability to pre-eclampsia/eclampsia and gestational hypertension is associated with CVD risk factors and occurrence of CVD events.
METHODS
We obtained genetic associations with HDPs from a genome-wide association study and used individual participant data from the UK Biobank to obtain genetic associations with CVD risk factors and CVD events (defined as myocardial infarction or stroke). In our primary analysis, we applied Mendelian randomisation using inverse-variance weighted regression analysis in ever pregnant women. In sensitivity analyses, we studied men and nulligravidae to investigate genetic liability to HDPs and CVD risk without the ability to experience the underlying phenotype.
RESULTS
Our primary analysis included 221 155 ever pregnant women (mean age 56.8 (SD 7.9) years) with available genetic data. ORs for CVD were 1.20 (1.02 to 1.41) and 1.24 (1.12 to 1.38) per unit increase in the log odds of genetic liability to pre-eclampsia/eclampsia and gestational hypertension, respectively. Furthermore, genetic liability to HDPs was associated with higher levels of systolic and diastolic blood pressure and younger age at hypertension diagnosis. Sensitivity analyses revealed no statistically significant differences when comparing the findings with those of nulligravidae and men.
CONCLUSIONS
Genetic liability to HDPs is associated with higher CVD risk, lower blood pressure levels and earlier hypertension diagnosis. Our study suggests similar findings in ever pregnant women, nulligravidae and men, implying biological mechanisms relating to HDPs are causally related to CVD risk.
Topics: Humans; Female; Pregnancy; Mendelian Randomization Analysis; Hypertension, Pregnancy-Induced; Middle Aged; Genome-Wide Association Study; Male; Cardiovascular Diseases; United Kingdom; Risk Assessment; Genetic Predisposition to Disease; Risk Factors; Pre-Eclampsia; Adult; Heart Disease Risk Factors; Polymorphism, Single Nucleotide
PubMed: 38148158
DOI: 10.1136/heartjnl-2023-323490 -
JTCVS Techniques Aug 2023
PubMed: 37555024
DOI: 10.1016/j.xjtc.2023.05.015 -
The Journal of Maternal-fetal &... Dec 2023Low-dose aspirin is recommended for pregnant individuals at high-risk of developing preeclampsia, but less is known about those that develop preeclampsia even while... (Clinical Trial)
Clinical Trial
BACKGROUND
Low-dose aspirin is recommended for pregnant individuals at high-risk of developing preeclampsia, but less is known about those that develop preeclampsia even while using prophylactic aspirin for preeclampsia prevention as the best course of treatment.
OBJECTIVES
The objective of this study is to investigate the risk factors with the highest risk of developing preeclampsia among pregnant individuals already using aspirin from high-risk obstetrical centers across five countries.
DESIGN
This is a secondary analysis of pregnant individuals from the Folic Acid Clinical Trial (FACT) who were using prophylactic aspirin before 16 weeks gestation. The FACT randomized control trial took place in 70 high risk obstetrical centers in Canada, United Kingdom, Australia, Jamaica, and Argentina between 2011-2015. Participants were included if they had any of the risk factors for preeclampsia: diabetes, chronic hypertension, twin pregnancy, history of preeclampsia, and/or obesity (Body Mass Index ≥35). The outcomes of interest were preeclampsia and preterm preeclampsia (<37 weeks). Log binomial regressions assessed factors significantly associated with any preeclampsia or preterm-preeclampsia (<37 weeks) using adjusted risk ratios (ARR) and 95% confidence intervals (CI).
RESULTS
There were 2296 pregnant individuals with complete information on aspirin included in this study. At baseline, all patients were at high risk of preeclampsia and were eligible for aspirin prophylaxis, however, only 660 (28.7%) were taking aspirin. Among the 660 pregnant individuals taking aspirin, 132 (20%) developed preeclampsia and 60 (9.09%) preterm preeclampsia. Among pregnant individuals using aspirin, the risks of preeclampsia were highest for twins (ARR:2.62, 95% CI: 1.68-4.11), history of preeclampsia (ARR: 2.42, 95% CI: 1.74-3.38), and hypertension (ARR:1.92, 95% CI: 1.37-2.69). Similar trends were found for preterm-preeclampsia for twins (ARR:4.10, 95% CI:2.15-7.82), history of preeclampsia (ARR:2.75, 95% CI:1.62-4.67), and hypertension (ARR:2.18, 95% CI:1.28-3.72). No significant differences were found for obesity or diabetes.
CONCLUSION
These findings suggest that individuals with twin pregnancies, a history of preeclampsia, or hypertension may not benefit from aspirin to the same extent as those with other complications such as obesity or diabetes. Careful clinical monitoring for these risks factors is recommended and future research into the effectiveness in these populations would increase our understanding of the current best practice of prophylactic aspirin use to prevent preeclampsia. Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Aspirin; Folic Acid; Hypertension; Obesity; Pre-Eclampsia; Pregnancy, High-Risk; Retrospective Studies; Risk Factors
PubMed: 37073421
DOI: 10.1080/14767058.2023.2200879 -
Aging Sep 2023Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with...
BACKGROUND
Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with caution due to confounding factors and reverse causation.
METHODS
We obtained genetic variants from genome-wide association studies including GM (N = 18,340) in MiBioGen Consortium as well as HDP (7,686 cases/115,893 controls) and specific subtypes in FinnGen Consortium. Then, Inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS methods were applied to examine the causal association. Reverse Mendelian randomization (RMR) and multivariable MR were performed to confirm the causal direction and adjust the potential confounders, respectively. Furthermore, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy.
RESULTS
The present study found causalities between eight gut microbial genera and HDP. The HDP-associated gut microbial genera identified by MR analyses varied in different subtypes. Specifically, our study found causal associations of , , , , and with GH, of (), (), , , and with PE, and of and with eclampsia, respectively.
CONCLUSIONS
This study first applied the MR approach to detect the causal relationships between GM and specific HDP subtypes. Our findings may promote the prevention and treatment of HDP targeted on GM and provide valuable insights to understand the mechanism of HDP in different subtypes from the perspective of GM.
Topics: Female; Pregnancy; Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Hypertension, Pregnancy-Induced; Mendelian Randomization Analysis
PubMed: 37698537
DOI: 10.18632/aging.205019 -
Journal of Clinical Hypertension... Sep 2023Blood pressure (BP) is the main driver of mortality with 12.8% of all deaths worldwide. Adolescents are not spared, precisely in Cameroon where they constitute more than...
Blood pressure (BP) is the main driver of mortality with 12.8% of all deaths worldwide. Adolescents are not spared, precisely in Cameroon where they constitute more than half of its population. The objective of our work was to describe the prevalence and risk factors of pre-hypertension and high blood pressure (HBP) among adolescents in Cameroonian schools. Descriptive study over 5 months; from January to May 2019. The study population consisted of students from private and public schools in the city of Douala. Sociodemographic, anthropometric, and personal background data were collected. Physical activity (PA) was assessed using the short International Physical Activity Questionnaire (IPAQ). Multivariate logistic regression was used to determine factors associated with pre-hypertension and HBP. Differences were considered significant for p < .05. We recruited 771 students with an average age of 16 ± 1 years with female predominance (51.4%). The prevalences of pre-hypertension and HBP were 6.6% and 3%, respectively. Overweight/obesity (OR = 4.6; p < .0001), hyperglycemia [(OR = 4.06; p = .001)] physical inactivity (OR = 1.85; p = .019), and public institutions (OR = 1.87; p = .02) were associated with pre-hypertension. Similarly, overweight/obesity (OR = 2.99; p = .022), hyperglycemia (OR = 14.05; p < .0001), and physical inactivity (OR = 8.58; p < .0001) were correlated with HBP. Pre-hypertension and HBP are high in Cameroonian school adolescents and their risk factors are overweight/obesity, hyperglycemia, and physical inactivity.
Topics: Humans; Female; Adolescent; Male; Hypertension; Overweight; Prevalence; Cameroon; Prehypertension; Risk Factors; Obesity; Blood Pressure; Hyperglycemia
PubMed: 37561361
DOI: 10.1111/jch.14711 -
Hypertension (Dallas, Tex. : 1979) Nov 2023Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress,...
BACKGROUND
Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress, hypertension, and maternal systemic organ damage. The transcription factor, PPARγ (peroxisome proliferator-activated receptor-γ) promotes healthy trophoblast differentiation but is dysregulated in the preeclampsia placenta. Our study identifies the beneficial impact of Rosiglitazone-mediated PPARγ-activation in the stressed preeclampsia placenta.
METHODS
We used first trimester placentas, preeclamptic and preterm control placentas, and human trophoblast cell lines to study PPARγ activation.
RESULTS
Induction of PPARγ activates cell growth and antioxidative stress pathways, including the gene, heme oxygenase 1 (). Protein expression of both PPARγ and HO1 (heme oxygenase 1) are reduced in preeclamptic placentas, but Rosiglitazone restores HO1 signaling in a PPARγ-dependent manner.
CONCLUSIONS
Restoring disrupted pathways by PPARγ in preeclampsia offers a potential therapeutic pathway to reverse placental damage, extending pregnancy duration, and reduce maternal sequelae. Future research should aim to understand the full scope of impaired PPARγ signaling in the human placenta and focus on compounds for safe use during pregnancy to prevent severe perinatal morbidity and mortality.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Heme Oxygenase-1; Placenta; PPAR gamma; Pre-Eclampsia; Rosiglitazone; Trophoblasts
PubMed: 37702083
DOI: 10.1161/HYPERTENSIONAHA.123.21645 -
Placenta Jan 2024Hypertensive disorders in pregnancy (HDP) are the leading cause of perinatal mortality worldwide. Inflammatory responses induced by insufficient placental perfusion have...
INTRODUCTION
Hypertensive disorders in pregnancy (HDP) are the leading cause of perinatal mortality worldwide. Inflammatory responses induced by insufficient placental perfusion have become a focal point in understanding the pathogenesis and aetiology of HDP and developing reliable and consistent biomarkers. Therefore, this study aims to identify gene signatures linked to the pathophysiology of HDP (gestational hypertension and early and late-onset pre-eclampsia).
METHODS
RNA was extracted from the maternal serum from the blood samples collected from different groups of HDP patients. A multiplex inflammation panel (255 inflammatory and housekeeping genes) and further gene expression analysis using NanoString Digital Direct Detection were done. The prominent expressions of these genes were further validated through qPCR techniques.
RESULTS
NanoString analysis identified nine unique, significantly expressed genes (MAPK1, MAPK3, MAFF, HLA-DRA, IL12B, RHOA, MASP2, MEF2A and NR3C1) between specific group comparisons of different HPD classes and the normotensive groups. The qPCR showed that the HLA-DRA gene was significantly upregulated in the early-onset pre-eclamptic and gestational hypertensive group compared to its respective normotensive group. In contrast, MAFF and MEF2A were significantly downregulated in both HDPs compared to their controls. The MAPK1 gene was significantly higher in the early-onset group compared to the gestational hypertensive and normotensive groups.
DISCUSSION
The upregulation of these distinctive genes in hypertensive groups compared to normotensives confirmed their diagnostic potential. Therefore, HLA-DRA, MAFF and MEF2A could be candidate markers of HDP, while the MAPK1 gene could be a differentiating marker between early-onset pre-eclampsia and gestational hypertension.
Topics: Humans; Female; Pregnancy; Hypertension, Pregnancy-Induced; Pre-Eclampsia; HLA-DR alpha-Chains; Placenta; Blood Pressure
PubMed: 38006650
DOI: 10.1016/j.placenta.2023.11.011 -
Journal of Clinical Medicine Feb 2024Natural disasters, such as floods and landslides caused by heavy rainfall, earthquakes, and tsunamis, can induce stress, which may contribute to the onset and... (Review)
Review
Natural disasters, such as floods and landslides caused by heavy rainfall, earthquakes, and tsunamis, can induce stress, which may contribute to the onset and aggravation of various cardiovascular diseases. The circulatory system is most susceptible to the effects of stress, and stress-related cardiovascular diseases, such as Takotsubo cardiomyopathy, pulmonary thromboembolism, hypertension, stroke triggered by increased blood pressure, and acute myocardial infarction, can occur during natural disasters. The risk of developing angina pectoris, arrhythmia, sudden cardiac death, and heart failure increases rapidly and can persist for several months. Moreover, treating cardiovascular diseases is essential during the acute phase, and continuous disease management is necessary during the chronic phase. However, disaster medical care for the victims must be given priority during natural disasters, which may cause a delay in diagnosis or access to necessary treatment for pre-existing medical conditions that could worsen or may cause death in patients with cardiovascular diseases. In this review, we summarize the predisposing factors for cardiovascular diseases that have been obtained through disasters such as major earthquakes and provide potential insights to help medical staff prevent the onset and aggravation of cardiovascular diseases during disasters.
PubMed: 38398317
DOI: 10.3390/jcm13041004 -
Physiological Genomics Jul 2023Mitochondrial dysfunction has been implicated in pregnancy-induced hypertension (PIH). The role of mitochondrial gene dysregulation in PIH, and consequences for...
Mitochondrial dysfunction has been implicated in pregnancy-induced hypertension (PIH). The role of mitochondrial gene dysregulation in PIH, and consequences for maternal-fetal interactions, remain elusive. Here, we investigated mitochondrial gene expression and dysregulation in maternal and placental tissues from pregnancies with and without PIH; further, we measured circulating mitochondrial DNA (mtDNA) mutational load, an index of mtDNA integrity. Differential gene expression analysis followed by Time Course Gene Set Analysis (TcGSA) was conducted on publicly available high throughput sequencing transcriptomic data sets. Mutational load analysis was carried out on peripheral mononuclear blood cells from healthy pregnant individuals and individuals with preeclampsia. Thirty mitochondrial differentially expressed genes (mtDEGs) were detected in the maternal cell-free circulating transcriptome, whereas nine were detected in placental transcriptome from pregnancies with PIH. In PIH pregnancies, maternal mitochondrial dysregulation was associated with pathways involved in inflammation, cell death/survival, and placental development, whereas fetal mitochondrial dysregulation was associated with increased production of extracellular vesicles (EVs) at term. Mothers with preeclampsia did not exhibit a significantly different degree of mtDNA mutational load. Our findings support the involvement of maternal mitochondrial dysregulation in the pathophysiology of PIH and suggest that mitochondria may mediate maternal-fetal interactions during healthy pregnancy. This study identifies aberrant maternal and fetal expression of mitochondrial genes in pregnancies with gestational hypertension and preeclampsia. Mitochondrial gene dysregulation may be a common etiological factor contributing to the development of de novo hypertension in pregnancy-associated hypertensive disorders.
Topics: Pregnancy; Female; Humans; Hypertension, Pregnancy-Induced; Placenta; Pre-Eclampsia; Genes, Mitochondrial; DNA, Mitochondrial
PubMed: 37184228
DOI: 10.1152/physiolgenomics.00005.2023 -
Journal of Clinical Medicine Aug 2023In this article, we discuss the topic of chronic thromboembolic pulmonary disease (CTEPD) and the growing role of balloon pulmonary angioplasty (BPA) in its treatment.... (Review)
Review
In this article, we discuss the topic of chronic thromboembolic pulmonary disease (CTEPD) and the growing role of balloon pulmonary angioplasty (BPA) in its treatment. We present the pathophysiology of CTEPD which arises from an incomplete resolution of thrombi in the pulmonary arteries and leads to stenosis and occlusion of the vessels. The article focuses mainly on the chronic thromboembolic pulmonary hypertension (CTEPH) subpopulation for which prognosis is very poor when left untreated. We describe a multimodal approach to treating CTEPH, including pulmonary endarterectomy (PEA), BPA, and pharmacological therapies. Additionally, the benefits of pharmacological pre-treatment before BPA and the technical aspects of the procedure itself are outlined. It is emphasized that BPA does not replace PEA but serves as a complementary treatment option for eligible patients. We summarized efficacy and treatment goals including an improvement in functional and biochemical parameters before and after BPA. Patients who received pre-treatment with riociguat prior to BPA exhibited a notable reduction in the occurrence of less severe complications. However, elderly patients are still perceived as an especially vulnerable group. It is shown that the prognosis of patients undergoing BPA is similar to PEA in the first years after the procedure but the long-term prognosis of BPA still remains unclear. The 2022 ESC/ERS guidelines highlight the significant role of BPA in the multimodal treatment of CTEPH, emphasizing its effectiveness and recommending its consideration as a therapeutic option for patients with CTEPD, both with and without pulmonary hypertension. This review summarizes the available evidence for BPA, patient selection, procedural details, and prognosis and discusses the potential future role of BPA in the management of CTEPH.
PubMed: 37629379
DOI: 10.3390/jcm12165336