Genetic Variation in Cardiometabolic Traits and Medication Targets and the Risk of Hypertensive Disorders of Pregnancy.
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ABSTRACT:
SUBMITTER: Honigberg MC
PROVIDER: S-EPMC7436942 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Genetic Variation in Cardiometabolic Traits and Medication Targets and the Risk of Hypertensive Disorders of Pregnancy.
Honigberg Michael C MC Chaffin Mark M Aragam Krishna K Bhatt Deepak L DL Wood Malissa J MJ Sarma Amy A AA Scott Nandita S NS Peloso Gina M GM Natarajan Pradeep P
Circulation 20200817 7
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Project description:AIMS:The cumulative effect of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) on postpartum cardio-metabolic diseases is equivocal. We aimed to assess the associations of GDM and HDP's individual and synergic contribution to risks of postpartum cardio-metabolic diseases (metabolic syndrome (MetS), abnormal glucose metabolism and hypertension (HTN)). METHODS:Of participants from a Singapore birth cohort, 276 mothers attending the 5-year postpartum visit were included in this study. During this visit, we collected mothers' history of GDM and HDP in all live births in a chronicle sequence and assessed the cardio-metabolic risks based on blood pressure, anthropometry and a panel of serum biomarkers. We diagnosed MetS, abnormal glucose metabolism and HTN according to Adult Treatment Panel III 2000 and World Health Organization guidelines. RESULTS:Of 276 mothers, 157 (56.9%) had histories of GDM while 23 (8.3%) had histories of HDP. After full adjustment, we found associations of GDM episodes with postpartum abnormal glucose metabolism (single episode: relative risk (RR) 2.9 (95% CI: 1.7, 4.8); recurrent episodes (≥2): RR = 3.8 (2.1-6.8)). Also, we found association between histories of HDP and HTN (RR = 3.6 (1.5, 8.6)). Having either (RR 2.6 (1.7-3.9)) or both gestational complications (RR 2.7 (1.6-4.9)) was associated with similar risk of postpartum cardio-metabolic disease. CONCLUSIONS:Mothers with GDM or HDP had a threefold increased risk of postpartum abnormal glucose metabolism or HTN, respectively. Having both GDM and HDP during past pregnancies was not associated with additional risk of postpartum cardio-metabolic diseases beyond that associated with either complication alone.
| S-EPMC5834770 | biostudies-literature
Project description:The objective of this study was to determine the associations between hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in the offspring. Therefore, 7794 women from the Generation Rotterdam Study were included, an ongoing population-based prospective birth cohort. Women with a hypertensive disorder of pregnancy were classified as such when they were affected by pregnancy induced hypertension, pre-eclampsia or the haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome during pregnancy. Early childhood cardiometabolic risk factors were defined as the body mass index at the age of 2, 6, 12, 36 months and 6 years. Additionally, it included systolic blood pressure, diastolic blood pressure, total fat mass, cholesterol, triglycerides, insulin and clustering of cardiometabolic risk factors at 6 years of age. Sex-specific differences in the associations between hypertensive disorders and early childhood cardiometabolic risk factors were investigated. Maternal hypertensive disorders of pregnancy were inversely associated with childhood body mass index at 12 months (confounder model: -0.15 SD, 95% CI -0.27; -0.03) and childhood triglyceride at 6 years of age (confounder model: -0.28 SD, 95% CI -0.45; -0.10). For the association with triglycerides, this was only present in girls. Maternal hypertensive disorders of pregnancy were not associated with childhood body mass index at 2, 6 and 36 months. No associations were observed between maternal hypertensive disorders of pregnancy and systolic blood pressure, diastolic blood pressure, body mass index, fat mass index and cholesterol levels at 6 years of age. Our findings do not support an independent and consistent association between maternal hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in their offspring. However, this does not rule out possible longer term effects of maternal hypertensive disorders of pregnancy on offspring cardiometabolic health.
| S-EPMC8699579 | biostudies-literature
Project description:ImportanceA genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.ObjectiveTo disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.Design, setting, and participantsThis GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant International Classification of Diseases codes. Data were analyzed from July 2020 to February 2023.ExposuresThe association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes.ResultsA total of 16 743 women with prior preeclampsia and 15 200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (PGR, TRPC6, ACTN4, and PZP), remodeling of uterine spiral arteries (NPPA, NPPB, NPR3, and ACTN4), kidney function (PLCE1, TNS2, ACTN4, and TRPC6), and maintenance of proteostasis in pregnancy serum (PZP).Conclusions and relevanceThe findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.
| S-EPMC10248811 | biostudies-literature
Project description:BackgroundUnhealthy sleep patterns are common during pregnancy and have been associated with an increased risk of developing hypertensive disorders of pregnancy (HDPs) in observational studies. However, the causality underlying these associations remains uncertain. This study aimed to evaluate the potential causal association between seven sleep traits and the risk of HDPs using a two-sample Mendelian randomization study.MethodsGenome-wide association study (GWAS) summary statistics were obtained from the FinnGen consortium, UK Biobank, and other prominent consortia, with a focus on individuals of European ancestry. The primary analysis utilized an inverse-variance-weighted MR approach supplemented by sensitivity analyses to mitigate potential biases introduced by pleiotropy. Furthermore, a two-step MR framework was employed for mediation analyses.ResultsThe data analyzed included 200 000-500 000 individuals for each sleep trait, along with approximately 15 000 cases of HDPs. Genetically predicted excessive daytime sleepiness (EDS) exhibited a significant association with an increased risk of HDPs [odds ratio (OR) 2.96, 95% confidence interval (95% CI) 1.40-6.26], and the specific subtype of preeclampsia/eclampsia (OR 2.97, 95% CI 1.06-8.3). Similarly, genetically predicted obstructive sleep apnea (OSA) was associated with a higher risk of HDPs (OR 1.27, 95% CI 1.09-1.47). Sensitivity analysis validated the robustness of these associations. Mediation analysis showed that BMI mediated approximately 25% of the association between EDS and HDPs, while mediating up to approximately 60% of the association between OSA and the outcomes. No statistically significant associations were observed between other genetically predicted sleep traits, such as chronotype, daytime napping, sleep duration, insomnia, snoring, and the risk of HDPs.ConclusionOur findings suggest a causal association between two sleep disorders, EDS and OSA, and the risk of HDPs, with BMI acting as a crucial mediator. EDS and OSA demonstrate promise as potentially preventable risk factors for HDPs, and targeting BMI may represent an alternative treatment strategy to mitigate the adverse impact of sleep disorders.
| S-EPMC11296273 | biostudies-literature
Project description:BackgroundHypertensive disorders of pregnancy (HDPs) are among the leading causes of maternal and perinatal morbidity and mortality worldwide and have been suggested to increase long-term cardiovascular disease risk in the offspring.ObjectiveThe objective of this study was to investigate whether HDPs are associated with cardiometabolic markers in childhood.Search strategyPubMed, The Cochrane Library and reference lists of included studies up to January 2019.Selection criteriaStudies comparing cardiometabolic markers in 2-18-year-old children of mothers with HDP in utero, to children of mothers without HDP.Data collection and analysisSixteen studies reported in 25 publications were included in this systematic review, of which three were considered as having high risk of bias. Thus 13 studies were included in the evidence synthesis: respectively two and eight reported pregnancy induced hypertension and preeclampsia, and three studies reported on both HDPs.Main resultsMost studies (n = 4/5) found a higher blood pressure in children exposed to pregnancy induced hypertension. Most studies (n = 7/10) found no statistically significantly higher blood pressure in children exposed to preeclampsia. No association was found between exposure to HDP and levels of cholesterol, triglycerides or glucose (n = 5/5). No studies investigated an association with (carotid) intima-media thickness, glycated haemoglobin or diabetes mellitus type 2.ConclusionsMost studies showed that exposure to pregnancy induced hypertension is associated with a higher offspring blood pressure. There is no convincing evidence for an association between exposure to preeclampsia and blood pressure in childhood. Based on current evidence, exposure to HDP is not associated with blood levels of cholesterol, triglycerides and glucose in childhood.
| S-EPMC6806146 | biostudies-literature
Project description:Background: Arterial hypertension is one of the most important causes of cardiovascular diseases, and the latter are responsible for almost half of the deaths in the industrialised nations. Hypertensive disorders of pregnancy constitute one of the most frequent causes of feto-maternal morbidity and mortality; on the other hand the occurrence of a hypertensive disorder of pregnancy represents a risk for the later development of hypertension and the cardiovascular risks resulting therefrom. The aim of this article is to demonstrate the association of hypertensive disorders of pregnancy with consecutive cardiovascular diseases. Materials and Methods: Specific selective literature research. Results: After the occurrence of a hypertensive disorder of pregnancy the relative risks for hypertension are 3.7 (2.70-5.05), for ischaemic heart disease 2.2 (1.86-2.52), for cerebral insult 1.8 (1.45-2.27) and for mortality resulting from cardiovascular causes 1.5 (1.05-2.14) and are thus significant. According to a recent study 56 % of internal specialists and 23 % of gynecologists do not know about the association of preeclampsia with ischemic heart disease, 48 % and 38 % respectively are not aware of the link with stroke and 79 % and 77 % respectively are not aware of the association with a reduced life expectancy after preeclampsia. The presence of hypertension is not known by many of the patients, merely 28-38 % receive an appropriate therapy. Conclusion: Adequate follow-up after hypertensive disorders of pregnancy and the early recognition of and therapy for hypertension represent the cornerstones in the prevention of late cardiovascular sequelae. General practitioners, specialist for internal medicine and gynaecologists have a special responsibility with regard to the reduction of later complications.
| S-EPMC3859153 | biostudies-literature
Project description:ImportanceHypertensive disorders of pregnancy are important causes of maternal and perinatal morbidity in the US. However, the extent of statewide variation in the prevalence of chronic hypertension, pregnancy-induced hypertension or preeclampsia, and eclampsia in the US remains unknown.ObjectiveTo examine the extent of statewide variation in the prevalence of chronic hypertension, hypertensive disorders of pregnancy (including pregnancy-induced hypertension or preeclampsia), and eclampsia in the US.Design, setting, and participantsA cross-sectional study using 2017 US birth certificate data was conducted from September 1, 2019, to February 1, 2020. A population-based sample of 3 659 553 women with a live birth delivery was included.Main outcomes and measuresState-specific prevalence of chronic hypertension, hypertensive disorders of pregnancy, and eclampsia was assessed using multilevel multivariable logistic regression, with the median odds ratio (MOR) to evaluate statewide variation.ResultsOf the 3 659 553 women, 185 932 women (5.1%) were younger than 20 years, 727 573 women (19.9%) were aged between 20 and 24 years, 1 069 647 women (29.2%) were aged between 25 and 29 years, 1 037 307 women (28.3%) were aged between 30 and 34 years, 523 607 women (14.3%) were aged between 35 and 39 years, and 115 487 women (3.2%) were 40 years or older. Most women had Medicaid (42.8%) or private insurance (49.4%). Hawaii had the lowest adjusted prevalence of chronic hypertension (1.0%; 95% CI, 0.9%-1.2%), and Alaska had the highest (3.4%; 95% CI, 3.0%-3.9%). Massachusetts had the lowest adjusted prevalence of hypertensive disorders of pregnancy (4.3%; 95% CI, 4.1%-4.6%), and Louisiana had the highest (9.3%; 95% CI, 8.9%-9.8%). Delaware had the lowest adjusted prevalence of eclampsia (0.03%; 95% CI, 0.01%-0.09%), and Hawaii had the highest (2.8%; 95% CI, 2.2%-3.4%). The degree of statewide variation was high for eclampsia (MOR, 2.36; 95% CI, 1.88-2.82), indicating that the median odds of eclampsia were 2.4-fold higher if the same woman delivered in a US state with a higher vs lower prevalence of eclampsia. Modest variation between states was observed for chronic hypertension (MOR, 1.27; 95% CI, 1.20-1.33) and hypertensive disorders of pregnancy (MOR, 1.17; 95% CI, 1.13-1.21).Conclusions and relevanceThe findings of this study suggest that after accounting for patient-level and state-level variables, substantial state-level variation exists in the prevalence of eclampsia. These data can inform future public-health inquiries to identify reasons for the eclampsia variability.
| S-EPMC7530635 | biostudies-literature
Project description:The genetic risk for hypertensive disorders of pregnancy is linked with the development of atherosclerotic cardiovascular disease. However, the effects of lifestyle and metabolic syndrome on atherosclerotic cardiovascular disease have not been evaluated. Here, we assess the long-term association between these factors and atherosclerotic cardiovascular disease in women with genetic risk for hypertensive disorders of pregnancy. We evaluate the genetic risk for hypertensive disorders of pregnancy using a genome-wide polygenic risk score derived from a large-scale GWAS. The incidence of atherosclerotic cardiovascular disease is evaluated according to genetic risk, lifestyle, and metabolic syndrome. Individuals with a very high genetic risk for hypertensive disorders of pregnancy have a 53.0% higher chance of developing atherosclerotic cardiovascular disease than those with a low genetic risk. However, the risk of developing atherosclerotic cardiovascular disease is reduced by up to 64.6% through the maintenance of an ideal metabolic syndrome status and a healthy lifestyle in the high genetic risk group (top 20%), and by up to 65.4% in the low genetic risk group (bottom 20%). These findings emphasize that maintaining a healthy lifestyle in women is equally effective at reducing the risk of atherosclerotic cardiovascular disease independent of genetic risk for hypertensive disorders of pregnancy.
| S-EPMC11806095 | biostudies-literature
Project description:Hypertension is the most common medical disorder occurring during pregnancy and a leading cause of maternal and perinatal morbidity and mortality. Accurate blood pressure measurement and the diagnosis and treatment of hypertensive disorders during pregnancy and in the postpartum period are pivotal to improve outcomes. This article details hemodynamic adaptations to pregnancy and provides an approach to the prevention, diagnosis, and management of hypertensive disorders of pregnancy (HDP) and hypertensive emergencies. In addition, it reviews optimal strategies for the care of women with hypertension during the fourth trimester and beyond to minimize future cardiovascular risk.
| S-EPMC7720658 | biostudies-literature
Project description:Background Breastfeeding is associated with improved cardiometabolic profiles decades after pregnancy. Whether this association exists for women who experience hypertensive disorders of pregnancy (HDP) is unknown. The authors examined whether breastfeeding duration or exclusivity are associated with long-term cardiometabolic health, and whether this relationship differs by HDP status. Methods and Results Participants (N=3598) were from the UK ALSPAC (Avon Longitudinal Study of Parents and Children) cohort. HDP status was assessed by medical record review. Breastfeeding behaviors were assessed by contemporaneous questionnaires. Breastfeeding duration was categorized as never, <1, 1 to <3, 3 to <6, 6 to <9, and 9+ months. Breastfeeding exclusivity was categorized as never, <1, 1 to <3, and 3 to 6 months. Measures of cardiometabolic health (body mass index, waist circumference, C-reactive protein, insulin, proinsulin, glucose, lipids, blood pressure, mean arterial pressure, carotid intima-media thickness, and arterial distensibility) were measured 18 years after pregnancy. Analyses were conducted using linear regression adjusting for relevant covariates. Breastfeeding was associated with improved cardiometabolic health (lower body mass index, waist circumference, C-reactive protein, triglycerides, insulin, and proinsulin) in all women, but not for every breastfeeding duration. Interaction tests revealed additional benefits in women with a history of HDP, with the strongest benefit observed in the 6- to 9-month breastfeeding category (diastolic blood pressure, -4.87 mm Hg [95% CI, -7.86 to -1.88], mean arterial pressure -4.61 [95% CI, -7.45 to -1.77], and low-density lipoprotein cholesterol, -0.40 mmol/L [95% CI, -0.62 to -0.17 mmol/L]). Differences in C-reactive protein and low-density lipoprotein "survived" Bonferroni correction (P<0.001). Similar results were observed in the exclusive breastfeeding analyses. Conclusions Breastfeeding may be a mechanism to reduce the cardiovascular disease sequela associated with HDP; however, there is a need to establish whether associations reflect a causal effect.
| S-EPMC10111449 | biostudies-literature