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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 -
Pharmacological Reports : PR Aug 2023Hypoxia-inducible factor (HIFs) is a new class of drug developed for the management of anemia in chronic kidney disease (CKD) patients. HIFs increase the production of... (Review)
Review
Hypoxia-inducible factor (HIFs) is a new class of drug developed for the management of anemia in chronic kidney disease (CKD) patients. HIFs increase the production of erythropoietin in the kidney and liver, enhance the absorption and utilization of iron, and stimulate the maturation and proliferation of erythroid progenitor cells. Besides, HIFs regulate many physiologic processes by orchestrating the transcription of hundreds of genes. Essential hypertension (HT) is an epidemic worldwide. HIFs play a role in many biological processes involved in the regulation of blood pressure (BP). In the current review, we summarize pre-clinical and clinical studies investigating the relationship between HIFs and BP regulation in patients with CKD, conflicting issues, and discuss future potential strategies.
Topics: Humans; Renal Insufficiency, Chronic; Anemia; Kidney; Erythropoietin; Essential Hypertension; Hypoxia
PubMed: 37210694
DOI: 10.1007/s43440-023-00497-x -
Vascular Pharmacology Aug 2023Pulmonary hypertension due to left heart disease (PH-LHD) or group 2 PH is the most common and lethal form of PH, occurring secondary to left ventricular systolic or... (Review)
Review
Pulmonary hypertension due to left heart disease (PH-LHD) or group 2 PH is the most common and lethal form of PH, occurring secondary to left ventricular systolic or diastolic heart failure (HF), left-sided valvular diseases, and congenital abnormalities. It is subdivided into isolated postcapillary PH (IpcPH) and combined pre- and post-capillary PH (CpcPH), with the latter sharing many similarities with group 1 PH. CpcPH is associated with worse outcomes and increased morbidity and mortality when compared to IpcPH. Although IpcPH can be improved by treatment of the underlying LHD, CpcPH is an incurable disease for which no specific treatment exists, likely due to the lack of understanding of its underlying mechanisms. Furthermore, drugs approved for PAH are not recommended for group 2 PH, as they are either ineffective or even deleterious. With this major unmet medical need, a better understanding of mechanisms and the identification of effective treatment strategies for this deadly condition are urgently needed. This review presents relevant background of the molecular mechanisms underlying PH-LHD that could translate into innovative therapeutic targets and explores novel targets currently being evaluated in clinical trials.
Topics: Humans; Hypertension, Pulmonary; Treatment Outcome; Ventricular Dysfunction, Left; Heart Failure
PubMed: 37178949
DOI: 10.1016/j.vph.2023.107180 -
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 -
PloS One 2023Hypertension (HTN) stands as the leading modifiable risk factor for cardiovascular disease(CVD) and premature death globally. Understanding its prevalence and risk...
Hypertension (HTN) stands as the leading modifiable risk factor for cardiovascular disease(CVD) and premature death globally. Understanding its prevalence and risk factors is essential for effective prevention and management of HTN. This study aimed to investigate the prevalence of Pre-hypertension (pre-HTN), HTN, and its risk factors in adults participating in the Zahedan adult cohort study (ZACS). This cross-sectional study used the baseline data of the ZACS. Ordinal logistic regression analysis was used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for potential risk factors. Among the 10,016 participants in this study, 60.89% were women, with an average age of 50.44 ± 9.18 years. The prevalence of pre-HTN and HTN was 42.03% (men 45.44%, women 39.84%) and 18.47% (men 21.09%, women 16.79%), respectively. Being male, older age, having higher socioeconomic status (SES), being overweight and obese, having a family history of HTN, comorbidities such as diabetes and CVD, as well as abnormal blood lipid levels (triglycerides and HDL cholesterol) were the most significant predictors of pre-HTN and HTN. These findings highlight that more than half of the participants in this study exhibit pre-HTN or HTN, placing them at risk for CVD and stroke. Implementing comprehensive preventive strategies tailored to these identified risk factors is imperative to alleviate the disease burden, enhance disease management, and improve HTN treatment and control.
Topics: Adult; Humans; Male; Female; Middle Aged; Cohort Studies; Prehypertension; Prevalence; Iran; Cross-Sectional Studies; Hypertension; Risk Factors; Surveys and Questionnaires
PubMed: 38060532
DOI: 10.1371/journal.pone.0295270 -
Hypertension (Dallas, Tex. : 1979) Sep 2023Hypertensive disorders of pregnancy (HDP) have been associated with an increased risk of chronic hypertension for both mothers and offspring. We sought to quantify the...
BACKGROUND
Hypertensive disorders of pregnancy (HDP) have been associated with an increased risk of chronic hypertension for both mothers and offspring. We sought to quantify the incidence of chronic hypertension in offspring from HDP-affected pregnancies in a large, population-based cohort study. Furthermore, we evaluate the association of HDP exposure in utero and maternal chronic hypertension in offspring.
METHODS
We performed a population-based cohort study of 8755 individuals born during 1976 to 1982 to 7544 women who all resided in the same community at the time of delivery. HDP were identified using a previously validated algorithm. Diagnosis of chronic hypertension in mothers and their offspring was determined using diagnostic codes. Cox proportional hazards regression was used to assess the association between HDP and chronic hypertension.
RESULTS
HDP exposure (hazard ratio, 1.50 [95% CI, 1.18-1.90]) and maternal chronic hypertension (hazard ratio, 1.73 [95% CI, 1.48-2.02]) were both associated with a significant increased risk for chronic hypertension in offspring. Both risk factors remained significantly associated with increased risk of hypertension in offspring when included together in a multivariate model. Having both exposures was associated with a 2.4-fold increase in the risk of hypertension in offspring, suggesting a synergistic additive interaction.
CONCLUSIONS
HDP exposure in gestation and maternal hypertension are both independently associated with an increased risk of chronic hypertension in offspring. Our results suggest that HDP exposure in utero, in addition to maternal chronic hypertension, may lead to a greater risk for the development of hypertension in offspring.
Topics: Pregnancy; Adult; Humans; Female; Hypertension, Pregnancy-Induced; Cohort Studies; Pre-Eclampsia; Risk Factors
PubMed: 37489531
DOI: 10.1161/HYPERTENSIONAHA.123.20282 -
European Journal of Obstetrics,... Nov 2023Pre-eclampsia and gestational hypertension are two common hypertensive disorders of pregnancy with pre-eclampsia accounting for high foetal and maternal morbidity and...
OBJECTIVE
Pre-eclampsia and gestational hypertension are two common hypertensive disorders of pregnancy with pre-eclampsia accounting for high foetal and maternal morbidity and mortality rate. These disorders have an unknown aetiology and their hypertensive and end-organ pathophysiology may present too late in pregnancy. This makes the identification of early detection and differentiation markers vital. MicroRNAs have strongly been associated with pregnancy and their imbalance has been associated with the angiogenic dysregulation seen in pre-eclampsia. This study assesses the expression of pro- and antiangiogenic factors and their corresponding microRNAs in the maternal circulation of patients with pre-eclampsia and gestational hypertension.
STUDY DESIGN
We analyzed angiogenic factors expression (sEng, TGF-β, VEGF) normalized against housekeeping gene β-actin and microRNAs (miRs: 210, 29B, 126) normalized against miR U6, potentially associated with pre-eclampsia and gestational hypertension using the targeted qPCR technique. These analytes were examined from early-onset (<34 weeks) (EOPE) (n = 12), late-onset (>34 weeks) (LOPE) (n = 12) pre-eclampsia, gestational hypertension (GH) (n = 12) and two gestationally matched normotensive groups (NG1 and 2) (n = 12) each in South African women of African ancestry. Group comparisons of experimental vs. control groups were assessed using t-test analysis for significance and represented as fold change expression.
RESULTS
The relative expression in group comparisons showed significant (p < 0.05) fold change of VEGF, TGF-β, sEng and miR126 in the EOPE vs. NG1. The GH vs. NG1 exhibited significant changes in VEGF, TGF-β, miR126, miR210 and miR29B. The LOPE vs. NG2 showed significant relative expression in all the angiogenic factors (VEGF, TGF-β and sEng). The GH vs. NG2 showed significant expression in VEGF and miR29B. The LOPE vs. EOPE showed significant fold changes in VEGF and miR210. Finally, only the GH vs. EOPE showed significant differences in miR210 and miR29B (p < 0.05).
CONCLUSION
This study provides better insights into angiogenic factors and microRNAs specificity to the subtypes of gestational hypertensive disorders in pregnancy. Relative expression analysis of angiogenic factors and microRNAs showed possible novel characteristics of gestational hypertension, and potential common molecular and pathological profiles with pre-eclampsia. Furthermore, we postulate that sEng and miR29B could be early detection markers for pre-eclampsia and gestational hypertension, respectively.
Topics: Pregnancy; Humans; Female; Pre-Eclampsia; Hypertension, Pregnancy-Induced; MicroRNAs; Vascular Endothelial Growth Factor A; Transforming Growth Factor beta
PubMed: 37716201
DOI: 10.1016/j.ejogrb.2023.09.012 -
Current Problems in Cardiology Mar 2024Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women.
METHODS
A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI).
RESULTS
A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved.
CONCLUSION
This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Calcium; Dietary Supplements; Randomized Controlled Trials as Topic
PubMed: 38013011
DOI: 10.1016/j.cpcardiol.2023.102217 -
JMIR Public Health and Surveillance Sep 2023A clear understanding of the anthropometric and sociodemographic risk factors related to BMI and hypertension categories is essential for more effective disease...
Prevalence, Regional Variations, and Predictors of Overweight, Obesity, and Hypertension Among Healthy Reproductive-Age Indian Women: Nationwide Cross-Sectional Polycystic Ovary Syndrome Task Force Study.
BACKGROUND
A clear understanding of the anthropometric and sociodemographic risk factors related to BMI and hypertension categories is essential for more effective disease prevention, particularly in India. There is a paucity of nationally representative data on the dynamics of these risk factors, which have not been assessed among healthy reproductive-age Indian women.
OBJECTIVE
This cross-sectional polycystic ovary syndrome (PCOS) task force study aimed to assess the anthropometric and sociodemographic characteristics of healthy reproductive-age Indian women and explore the association of these characteristics with various noncommunicable diseases.
METHODS
We conducted a nationwide cross-sectional survey from 2018 to 2022 as part of the Indian Council of Medical Research-PCOS National Task Force study, with the primary aim of estimating the national prevalence of PCOS and regional phenotypic variations among women with PCOS. A multistage random sampling technique was adopted, and 7107 healthy women (aged 18-40 years) from 6 representative geographical zones of India were included in the study. The anthropometric indices and sociodemographic characteristics of these women were analyzed. Statistical analysis was performed to assess the association between exposure and outcome variables.
RESULTS
Of the 7107 study participants, 3585 (50.44%) were from rural areas and 3522 (49.56%) were from urban areas. The prevalence of obesity increased from 8.1% using World Health Organization criteria to 40% using the revised consensus guidelines for Asian Indian populations. Women from urban areas showed higher proportions of overweight (524/1908, 27.46%), obesity (775/1908, 40.62%), and prehypertension (1008/1908, 52.83%) categories. A rising trend of obesity was observed with an increase in age. Women aged 18 to 23 years were healthy (314/724, 43.4%) and overweight (140/724, 19.3%) compared with women aged 36 to 40 years with obesity (448/911, 49.2%) and overweight (216/911, 23.7%). The proportion of obesity was high among South Indian women, with 49.53% (531/1072) and 66.14% (709/1072), using both World Health Organization criteria and the revised Indian guidelines for BMI, respectively. BMI with waist circumference and waist-to-height ratio had a statistically significant linear relationship (r=0.417; P<.001 and r=0.422; P<.001, respectively). However, the magnitude, or strength, of the association was relatively weak (0.3<|r|<0.5). Statistical analysis showed that the strongest predictors of being overweight or obese were older age, level of education, wealth quintile, and area of residence.
CONCLUSIONS
Anthropometric and sociodemographic characteristics are useful predictors of overweight- and obesity-related syndromes, including prehypertension, among healthy Indian women. Increased attention to the health of Indian women from public health experts and policy makers is warranted. The findings of this study can be leveraged to offer valuable insights, informing health decision-making and targeted interventions that mitigate risk factors of overweight, obesity, and hypertension.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
RR2-10.2196/23437.
Topics: Female; Humans; Overweight; Cross-Sectional Studies; Polycystic Ovary Syndrome; Prehypertension; Prevalence; Obesity
PubMed: 37672315
DOI: 10.2196/43199 -
American Journal of Hypertension Jan 2024
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Arteries; Heart Rate; Hypertension
PubMed: 37738220
DOI: 10.1093/ajh/hpad086