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High Blood Pressure & Cardiovascular... Jul 2023Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between... (Review)
Review
Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between pre-existing (chronic) hypertension and gestational hypertension, developing after 20 weeks of gestation and usually resolving within 6 weeks postpartum. There is a consensus that systolic blood pressure ≥ 170 or diastolic blood pressure ≥ 110 mmHg is an emergency and hospitalization is indicated. The selection of the antihypertensive drug and its route of administration depend on the expected time of delivery. The current European guidelines recommend initiating drug treatment in pregnant women with persistent elevation of blood pressure ≥ 150/95 mmHg and at values > 140/90 mmHg in women with gestational hypertension (with or without proteinuria), with pre-existing hypertension with the superimposition of gestational hypertension, and with hypertension with subclinical organ damage or symptoms at any time during pregnancy. Methyldopa, labetalol, and calcium antagonists (the most data are available for nifedipine) are the drugs of choice. The results of the CHIPS and CHAP studies are likely to reduce the threshold for initiating treatment. Women with a history of hypertensive disorders in pregnancy, particularly those with pre-eclampsia, are at high risk of developing cardiovascular disease later in life. Obstetric history should become a part of the cardiovascular risk assessment in women.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Hypertension, Pregnancy-Induced; Hypertension; Pre-Eclampsia; Antihypertensive Agents; Blood Pressure; Labetalol
PubMed: 37308715
DOI: 10.1007/s40292-023-00582-5 -
Kidney360 Oct 2023Hypertensive disorders of pregnancy complicate up to 10% of pregnancies and remain the major cause of maternal and neonatal morbidity and mortality. Hypertensive... (Review)
Review
Hypertensive disorders of pregnancy complicate up to 10% of pregnancies and remain the major cause of maternal and neonatal morbidity and mortality. Hypertensive disorders of pregnancy can be classified into four groups depending on the onset of hypertension and the presence of target organ involvement: chronic hypertension, preeclampsia, gestational hypertension, and superimposed preeclampsia on chronic hypertension. Hypertension during pregnancy is associated with a higher risk of cardiovascular disease and kidney failure. Early diagnosis and proper treatment for pregnant women with hypertension remain a priority since this leads to improved maternal and fetal outcomes. Labetalol, nifedipine, methyldopa, and hydralazine are the preferred medications to treat hypertension during pregnancy. In this comprehensive review, we discuss the diagnostic criteria, evaluation, and management of pregnant women with hypertension.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Antihypertensive Agents; Labetalol; Nifedipine
PubMed: 37526641
DOI: 10.34067/KID.0000000000000228 -
Hypertension Research : Official... Aug 2023Preeclampsia is a hypertensive disorder in pregnancy characterized by placental malperfusion and subsequent multi-organ injury. It accounts for approximately 14% of... (Review)
Review
Preeclampsia is a hypertensive disorder in pregnancy characterized by placental malperfusion and subsequent multi-organ injury. It accounts for approximately 14% of maternal deaths and 10-25% of perinatal deaths globally. In addition, preeclampsia has been attracting attentions for its association with risks for developing chronic diseases in later life for both mother and child. This mini-review discusses on latest knowledge on prediction, prevention, management, and long-term outcomes of preeclampsia and also touches on association between COVID-19 and preeclampsia. HTN hypertension, HDP hypertensive disorders of pregnancy, PE preeclampsia, BP blood pressure, cfDNA cell-free DNA, ST2 human suppression of tumorigenesis 2, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor, VEGF vascular endothelial growth factor, VEGFR VEGF receptor, TGFβ transforming growth factor β, ENG endoglin, sENG soluble ENG, PRES posterior reversible encephalopathy syndrome, AKI acute kidney injury, CVD cardiovascular disease, ESKD end-stage kidney disease, ACE angiotensinogen converting enzyme, Ang angiotensin.
Topics: Female; Humans; Pregnancy; Biomarkers; COVID-19; Endoglin; Hypertension; Placenta; Placenta Growth Factor; Posterior Leukoencephalopathy Syndrome; Pre-Eclampsia; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1
PubMed: 37268721
DOI: 10.1038/s41440-023-01323-w -
JAMA Cardiology Jul 2023A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.
IMPORTANCE
A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.
OBJECTIVE
To 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 PARTICIPANTS
This 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.
EXPOSURES
The association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes.
RESULTS
A 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 RELEVANCE
The 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.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Genome-Wide Association Study; TRPC6 Cation Channel; Placenta; Risk Factors
PubMed: 37285119
DOI: 10.1001/jamacardio.2023.1312 -
Cell Reports. Medicine Jul 2023Direct diagnosis and accurate assessment of metabolic syndrome (MetS) allow for prompt clinical interventions. However, traditional diagnostic strategies overlook the...
Direct diagnosis and accurate assessment of metabolic syndrome (MetS) allow for prompt clinical interventions. However, traditional diagnostic strategies overlook the complex heterogeneity of MetS. Here, we perform metabolomic analysis in 13,554 participants from the natural cohort and identify 26 hub plasma metabolic fingerprints (PMFs) associated with MetS and its early identification (pre-MetS). By leveraging machine-learning algorithms, we develop robust diagnostic models for pre-MetS and MetS with convincing performance through independent validation. We utilize these PMFs to assess the relative contributions of the four major MetS risk factors in the general population, ranked as follows: hyperglycemia, hypertension, dyslipidemia, and obesity. Furthermore, we devise a personalized three-dimensional plasma metabolic risk (PMR) stratification, revealing three distinct risk patterns. In summary, our study offers effective screening tools for identifying pre-MetS and MetS patients in the general community, while defining the heterogeneous risk stratification of metabolic phenotypes in real-world settings.
Topics: Humans; Metabolic Syndrome; Risk Factors; Obesity; Hypertension; Risk Assessment
PubMed: 37467725
DOI: 10.1016/j.xcrm.2023.101109 -
European Heart Journal Nov 2023Observational 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]) with available genetic data. Odds ratios for CVD were 1.20 (1.02-1.41) and 1.24 (1.12-1.38) 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 to 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: Female; Humans; Middle Aged; Pregnancy; Cardiovascular Diseases; Eclampsia; Genome-Wide Association Study; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Risk Factors; Mendelian Randomization Analysis
PubMed: 38304335
DOI: 10.1093/eurheartj/ehad655.2726 -
Lipids in Health and Disease Aug 2023It is well known that pregnancy-induced hypertension (PIH) contributes significantly to the mortality rates of both mothers and babies during pregnancy. The relationship...
BACKGROUND
It is well known that pregnancy-induced hypertension (PIH) contributes significantly to the mortality rates of both mothers and babies during pregnancy. The relationship between fatty acids (FAs) and PIH remains debatable, with the causality between the two yet to be definitively established.
METHODS
Two-sample univariable and multivariable Mendelian Randomization (MR) analyses were executed, based on pooled data from Genome-Wide Association Studies (GWAS), to investigate any causal impact of FAs on PIH. A suite of methods was employed to assess causality, including inverse variance weighting (IVW), weighted median, MR Egger, simple mode, and weighted mode. Subsequently, the data underwent a sensitivity analysis (using Leave-One-Out analysis), a heterogeneity test (with MR-PRESSO and Cochran's Q test), as well as a multiple validity test (using MR-Egger regression). In multivariable analyses, fatty acids were first grouped to observe the effect of individual FAs on PIH. Subsequently, factors such as diabetes, high blood pressure, and body mass index (BMI) were incorporated into a multivariable examination of the impact of each FA on PIH. During this process, the IVW, weighted median, MR-Lasso, and MR-Egger methods were employed.
RESULTS
A systematic investigation was conducted into the causal impact of each FA on PIH. The findings indicated that Polyunsaturated Fatty Acids (PUFA), Omega3, the ratio of Omega6 to Omega3, and Docosahexaenoic Acid (DHA) have a causal relationship with PIH. Increases in PUFA, Omega3, and DHA could potentially reduce the risk of PIH, while an increase in the Omega6/Omega3 ratio could heighten the risk. The impacts of other FAs (including Total Fatty Acids, Monounsaturated Fatty Acids (MUFA), Saturated Fatty Acids (SFA), and Omega 6) on PIH were not substantiated by the MR analysis. In the univariate leave-one-out analysis, rs174564 was identified in PUFA, Omega3, and DHA as having a significant role. The tests with MR-Egger and MR-PRESSO found that the results were not influenced by pleiotropy and heterogeneity. After adjusting for BMI, Diabetes Mellitus, and pre-existing hypertension in the multivariable analysis, the results mirrored those obtained univariable.
CONCLUSION
The research implies that elevated levels of circulating PUFA, DHA, and Omega3 may serve as a protective mechanism against PIH, while higher Omega6/Omega3 ratios could potentially increase the risk of PIH. These findings may inform clinical strategies for PIH prevention.
Topics: Infant; Female; Pregnancy; Humans; Fatty Acids; Hypertension, Pregnancy-Induced; Genome-Wide Association Study; Mendelian Randomization Analysis; Fatty Acids, Omega-3; Docosahexaenoic Acids
PubMed: 37587460
DOI: 10.1186/s12944-023-01889-x