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Frontiers in Immunology 2023Hypertensive disorders of pregnancy (HDP) pose a significant risk to maternal and fetal well-being; however, the etiology and pathogenesis of HDP remain ambiguous. It is...
BACKGROUND
Hypertensive disorders of pregnancy (HDP) pose a significant risk to maternal and fetal well-being; however, the etiology and pathogenesis of HDP remain ambiguous. It is now widely acknowledged that inflammatory response and the immune system are closely related to HDP. Previous research has identified several inflammatory cytokines are associated with HDP. This study applied Mendelian randomization (MR) analysis to further assess causality.
METHODS
Patients with HDP who participated in the MR analysis presented with four types of HDP: pre-eclampsia or eclampsia (PE); gestational hypertension (GH); pre-existing hypertension complicating pregnancy, childbirth and the puerperium (EH); and pre-eclampsia or poor fetal growth (PF). A two-sample MR analysis was used to analyze the data in the study. The causal relationship between exposure and outcome was analyzed with inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and simple mode methods, where IVW was the primary method employed.
RESULTS
Our MR analysis demonstrated a reliable causative effect of Interleukin-9 (IL-9) and macrophage migration inhibitory factor (MIF) on reducing HDP risk, while macrophage inflammatory protein 1-beta (MIP1b), Interleukin-13 (IL-13), and Interleukin-16 (IL-16) were associated with promoting HDP risk.
CONCLUSIONS
This study demonstrated that IL-9, MIF, MIP1b, IL-13, and IL-16 may be cytokines associated with the etiology of HDP, and that a number of inflammatory cytokines are probably involved in the progression of HDP. Additionally, our study revealed that these inflammatory cytokines have causal associations with HDP and may likely be potential therapeutic targets for HDP.
Topics: Female; Pregnancy; Humans; Interleukin-9; Hypertension, Pregnancy-Induced; Interleukin-13; Pre-Eclampsia; Interleukin-16; Mendelian Randomization Analysis
PubMed: 38035087
DOI: 10.3389/fimmu.2023.1297929 -
Methodist DeBakey Cardiovascular Journal 2024According to the American College of Obstetricians and Gynecologists (ACOG), women who have a systolic blood pressure ≥ 140 mm Hg and/or a diastolic pressure ≥ 90 mm... (Review)
Review
According to the American College of Obstetricians and Gynecologists (ACOG), women who have a systolic blood pressure ≥ 140 mm Hg and/or a diastolic pressure ≥ 90 mm Hg before pregnancy or before 20 weeks of gestation have chronic hypertension. Up to 1.5% of women in their childbearing years have a diagnosis of chronic hypertension, and 16% of pregnant women develop hypertension during their pregnancy. Physiological cardiovascular changes from pregnancy may mask or exacerbate hypertensive diseases during gestation, which is why prepregnancy counseling is emphasized for all patients to optimize comorbidities and establish a patient's baseline blood pressure. This review provides an overview of the diagnoses and treatments of hypertensive diseases that can occur in pregnancy, including definitions of key terms and types of hypertension as well as ACOG recommendations.
Topics: Female; Pregnancy; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Blood Pressure
PubMed: 38495660
DOI: 10.14797/mdcvj.1305 -
JAMA Nov 2023Pregnancy hypertension results in adverse cardiac remodeling and higher incidence of hypertension and cardiovascular diseases in later life. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Pregnancy hypertension results in adverse cardiac remodeling and higher incidence of hypertension and cardiovascular diseases in later life.
OBJECTIVE
To evaluate whether an intervention designed to achieve better blood pressure control in the postnatal period is associated with lower blood pressure than usual outpatient care during the first 9 months postpartum.
DESIGN, SETTING, AND PARTICIPANTS
Randomized, open-label, blinded, end point trial set in a single hospital in the UK. Eligible participants were aged 18 years or older, following pregnancy complicated by preeclampsia or gestational hypertension, requiring antihypertensive medication postnatally when discharged. The first enrollment occurred on February 21, 2020, and the last follow-up, November 2, 2021. The follow-up period was approximately 9 months.
INTERVENTIONS
Participants were randomly assigned 1:1 to self-monitoring along with physician-optimized antihypertensive titration or usual postnatal care.
MAIN OUTCOMES AND MEASURES
The primary outcome was 24-hour mean diastolic blood pressure at 9 months postpartum, adjusted for baseline postnatal blood pressure.
RESULTS
Two hundred twenty participants were randomly assigned to either the intervention group (n = 112) or the control group (n = 108). The mean (SD) age of participants was 32.6 (5.0) years, 40% had gestational hypertension, and 60% had preeclampsia. Two hundred participants (91%) were included in the primary analysis. The 24-hour mean (SD) diastolic blood pressure, measured at 249 (16) days postpartum, was 5.8 mm Hg lower in the intervention group (71.2 [5.6] mm Hg) than in the control group (76.6 [5.7] mm Hg). The between-group difference was -5.80 mm Hg (95% CI, -7.40 to -4.20; P < .001). Similarly, the 24-hour mean (SD) systolic blood pressure was 6.5 mm Hg lower in the intervention group (114.0 [7.7] mm Hg) than in the control group (120.3 [9.1] mm Hg). The between-group difference was -6.51 mm Hg (95% CI, -8.80 to -4.22; P < .001).
CONCLUSIONS AND RELEVANCE
In this single-center trial, self-monitoring and physician-guided titration of antihypertensive medications was associated with lower blood pressure during the first 9 months postpartum than usual postnatal outpatient care in the UK.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04273854.
Topics: Female; Humans; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Hypertension; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Self-Management; Adult; Postnatal Care
PubMed: 37950919
DOI: 10.1001/jama.2023.21523 -
Clinical Kidney Journal Sep 2023Systemic hypertension is the most common medical comorbidity affecting the adult population globally, with multiple associated outcomes including cerebrovascular... (Review)
Review
Systemic hypertension is the most common medical comorbidity affecting the adult population globally, with multiple associated outcomes including cerebrovascular diseases, cardiovascular diseases, vascular calcification, chronic kidney disease, metabolic syndrome and mortality. Despite advancements in the therapeutic field approximately one in every five adult patients with hypertension is classified as having treatment-resistant hypertension, indicating the need for studies to provide better understanding of the underlying pathophysiology and the need for more therapeutic targets. Recent pre-clinical studies have demonstrated the role of the innate and adaptive immune system including various cell types and cytokines in the pathophysiology of hypertension. Moreover, pre-clinical studies have indicated the potential beneficial effects of immunosuppressant medications in the control of hypertension. Nevertheless, it is unclear whether such pathophysiological mechanisms and therapeutic alternatives are applicable to human subjects, while this area of research is undoubtedly a rapidly growing field.
PubMed: 37664577
DOI: 10.1093/ckj/sfad059 -
Clinical Science (London, England :... Aug 2023The placental syndromes gestational hypertension, preeclampsia and intrauterine growth restriction are associated with an increased cardiovascular risk to the mother... (Review)
Review
The placental syndromes gestational hypertension, preeclampsia and intrauterine growth restriction are associated with an increased cardiovascular risk to the mother later in life. In this review, we argue that a woman's pre-conception cardiovascular health drives both the development of placental syndromes and long-term cardiovascular risk but acknowledge that placental syndromes can also contribute to future cardiovascular risk independent of pre-conception health. We describe how preclinical studies in models of preeclampsia inform our understanding of the links with later cardiovascular disease, and how current pre-pregnancy studies may explain relative contributions of both pre-conception factors and the occurrence of placental syndromes to long-term cardiovascular disease.
Topics: Pregnancy; Female; Humans; Cardiovascular Diseases; Pre-Eclampsia; Syndrome; Placenta; Cardiovascular System
PubMed: 37606085
DOI: 10.1042/CS20211130 -
European Heart Journal Apr 2024Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear.
METHODS
From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy.
RESULTS
Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)].
CONCLUSIONS
Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.
Topics: Humans; Renin-Angiotensin System; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Hypertension; Hypotension; Angiotensin Receptor Antagonists
PubMed: 37935833
DOI: 10.1093/eurheartj/ehad716 -
International Journal of Molecular... Feb 2024Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan... (Review)
Review
Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan dysfunction. Chronic kidney disease is an established risk factor for the development of pre-eclampsia, as angiogenic homeostasis is altered and the maternal circulation is already hypertensive. Facing pre-eclampsia in the context of chronic kidney disease is a challenging emergency for both the mother and the fetus. The clinical features and the management of this multi-organ disorder are clearly defined in the modern literature but the underlying pathophysiologic mechanisms remain not fully elucidated. Understanding the pathophysiology that mediates the onset of pre-eclampsia itself and in synergy with chronic kidney disease is fundamental for developing prompt prevention strategies, treatment planning, and patient counseling. This review aims to summarize the main molecular mechanisms involved in the process of pre-eclampsia, with a particular focus on the role of the kidneys and hormonal pathways related to renal function in normal pregnancy and pre-eclamptic syndromes.
Topics: Pregnancy; Female; Humans; Placenta; Pre-Eclampsia; Kidney; Hypertension; Renal Insufficiency, Chronic
PubMed: 38473987
DOI: 10.3390/ijms25052741 -
International Journal of Molecular... Feb 2024Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage.... (Review)
Review
Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area.
Topics: Humans; Female; Chromogranin A; Pre-Eclampsia; Peptide Fragments; Hypertension
PubMed: 38473713
DOI: 10.3390/ijms25052461