History Of Normotensive Pregnancy Research Articles

A Novel Stem Cell Model to Study Preeclampsia Endothelial Dysfunction

Preeclampsia is a common pregnancy complication affecting 5% to 7% of all pregnancies worldwide annually. While the pathogenesis is not fully understood, maternal endothelium dysfunction is thought to be a central component to preeclampsia development. Studies to dissect maternal endothelial dysfunction, particularly on a patient-specific basis, are hampered by limited access to systemic primary endothelial cells (ECs). The objective of this study was to establish a replenishable, patient-specific in vitro EC model to allow robust mechanistic studies to dissect endothelial dysfunction in preeclampsia. Induced pluripotent stem cells (iPSCs) from three women with a history of normotensive pregnancies were differentiated into ECs. The established ECs were exposed to pooled sera from normotensive pregnancies, preeclamptic pregnancies, normotensive postpartum for non-pregnant comparison and controls. Endothelial functions including nitric oxide (NO) release, cell migration, tube formation and viability were evaluated. Levels of NO release were significantly lower after incubation with preeclamptic sera compared to the fetal bovine serum (FBS) control, and normotensive and non-pregnant (postpartum) sera treatments were also lower than FBS but higher than preeclamptic sera treatments. Tube formation and cell migration were also impaired with preeclamptic sera compared to FBS controls. Cell viabilities remained unaffected by any sera treatment. Consistent outcomes were obtained across all three patient-specific lines treated with the same pooled sera. Establishment of patient-derived iPSC-ECs treated with pregnancy sera serves as a novel model to explore the interplay between individual maternal endothelial health and circulating factors that lead to endothelial dysfunction in preeclampsia.

Changes of Serum Angiotensin Peptides, Pro-Endothelin-1 Levels in Women One Year After Preeclampsia and their Association with Cardiovascular Risk Factors

Abstract Introduction Women who suffered preeclampsia (PE) have two to four times higher risk for development of cardiovascular disease (CVD) compared with women with a history of normotensive pregnancy. Microvascular and endothelial dysfunction, mediated by different vasoactive factors have been suggested as attainable pathophysiological pathways. The study aimed to: (1) determine changes in circulating levels of key vasoactive peptides in sera of women with history of PE and in women who had a normal pregnancy 1 year after delivery and (2) investigate whether an association exists between these molecules and cardiovascular risk factors. Materials and methods The current research examined 32 women one year after preeclampsia (mean age 25.3 ± 6.3 years) and control group of 20 women one year after normal pregnancy (mean age 25.6 ± 5.6 years). The enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of angiotensin II (AngII), angiotensin-(1-7) [Ang-(1-7)] and pro-endothelin-1 (Pro-ET-1). Results We found that at 1 year after delivery 38.46% of women who suffered PE have developed hypertension and 5.77% have developed diabetes mellitus. Women who had normal pregnancy developed neither hypertension, nor diabetes mellitus 1 year after delivery. Serum AngII levels in women one year after PE were statistically significantly lower than in women one year after normotensive pregnancy 0.9 (0.55÷1.7) vs. 2.3 pg/ml (2.0 ÷ 2.9) (KW = 20.849; p = 0.0001). Ang-(1-7) concentrations in women one year after PE were lower than in women one year after normal pregnancy, but not significantly 1.7 (0.3÷4.5) vs. 3.2 ng/ml (0.2÷8.0) (p>0.05). Levels of serum Pro-ET-1 in women one year after PE were statistically significantly higher than in women one year after normal pregnancy 322.65 (261.75÷391.85) vs. 248.7 pmol/L (231.05÷282.15) (KW = 6.639; p = 0.009). AngII showed correlation with AH grade (r = -0.33; 0.02), Ang-(1-7) (r = 0.27; 0.05), DBP (r = -0.28; p = 0.04), mean arterial pressure (r = -0.43; p = 0.002), pulse pressure (r = -0.28; p = 0.04), BMI (r = -0.30; p = 0.03), TC (r = -0.31; p = 0.03) and LDL (r = -0.30; p = 0.03). Pro-ET-1 correlated with age (r = 0.30; p = 0.03), mean arterial pressure (r = -0.25; p = 0.05) and pulse pressure (r = 0.41; p = 0.003). Conclusion Our data showed an association between key vasoactive peptides and major CVD risk factors in women one year after PE. We suggest that imbalance between AngII, Ang-(1-7) and Pro-ET-1 could have a potential imply on the vascular wall after PE, reflecting persistent microvascular and endothelial injury/dysfunction postpartum. Further studies are warranted to clarify these vasoactive peptides’ role in the ongoing vascular endothelial function after delivery and the pathogenic mechanisms determining development of CVD in previously PE women.

Cerebral volume is unaffected after pre-eclampsia.

Pre-eclampsia has been associated with cardiovascular, cerebrovascular and/or psychological complaints. Signs of altered brain morphology and more white-matter hyperintensities (WMHs) during and shortly after pre-eclampsia have been observed in some, but not all, studies. We compared volumes of cerebral structures and the number of WMHs between formerly pre-eclamptic women and those with normotensive gestational history and assessed the effect of age on brain volumes. Structural 7-Tesla magnetic resonance imaging of the brain was performed in 59 formerly pre-eclamptic women (aged 37 ± 6 years, 0.5-16 years postpartum) and 20 women with a history of normotensive pregnancy (aged 39 ± 5 years, 1-18 years postpartum). Fazekas scores were obtained to assess WMH load. Volumes of the whole brain, gray and white matter, brain lobes, and ventricular and pericortical cerebrospinal fluid (CSF) spaces were calculated after semiautomatic segmentation. Group differences were analyzed using ANCOVA and Bayes factors. Results were adjusted for age, educational attainment, presence of current hypertension and total intracranial volume. The effect of age on cerebral volumes was analyzed using linear regression analysis. No changes in global and local brain volumes were observed between formerly pre-eclamptic and control women. Also, no difference in WMH load was observed. Independent of pre-eclamptic history, gray-matter volume significantly decreased with age, while ventricular and pericortical CSF space volumes significantly increased with age. Volumetric changes of the cerebrum are age-related but are independent of pre-eclamptic history in the first two decades after childbirth. No evidence of greater WMH load after pre-eclampsia was found. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cardiometabolic profile in women after pregnancy hypertension: propency score matching

Оbjective: to assess the cardiometabolic profile and cardiovascular risk factors in women with a history of hypertension during pregnancy. Materials and methods: a case-control observational study based on a prospective cohort study included 66 women, divided into two groups: group 1 — with a history of hypertension during pregnancy (n=33), and group 2 (control) — with a history of normotensive pregnancy (n=33). We applied the propensity score -matching method. Results: women in group 1 women were more often had hypertension and obesity compared with the control group. The most significant changes in the cardiometabolic profile were found in group 1: the highest concentrations of glucose and immunoreactive insulin, glycated hemoglobin, uric acid, alanine aminotransferase, aspartate aminotransferase, C-reactive protein in serum, and HOMA-IR insulin resistance index. An increased left ventricular (LV) mass index and the urine albumin/ creatinine ratio were higher among women in group 1 compared with group 2. Conclusion: after applying the propensity score matching, the most significant differences were obtained in the frequency of hypertension, serum concentrations of alanine aminotransferase, C-reactive protein, and the frequency of elevated albumin/creatinine ratio.

Pre-eclampsia and cardiovascular risk: a long-term nationwide cohort study on over 120 000 Finnish women

ObjectivesTo investigate the impact of pre-eclampsia on the future cardiovascular risk in Finnish womenDesignA registry-based nationwide controlled cohort study.SettingWomen hospitalised for pre-eclampsia in 1969–1993 and control women with a history...

Blood-brain barrier leakage years after pre-eclampsia: dynamic contrast-enhanced 7-Tesla MRI study.

Pre-eclampsia is a hypertensive complication of pregnancy that is associated with an increased risk of long-term cardiovascular and cerebrovascular disorders. Although the underlying mechanism of persistent susceptibility to cerebral complications after pre-eclampsia remains largely unclear, impaired blood-brain barrier (BBB) integrity has been suggested to precede several cerebrovascular diseases. In this study, we aimed to investigate the integrity of the BBB years after pre-eclampsia. This was an observational study of premenopausal formerly pre-eclamptic women and controls with a history of normotensive pregnancy who underwent cerebral magnetic resonance imaging (MRI) at ultra-high field (7Tesla) to assess the integrity of the BBB. Permeability of the BBB was determined by assessing leakage rate and fractional leakage volume of the contrast agent gadobutrol using dynamic contrast-enhanced MRI. BBB leakage measures were determined for the whole brain and lobar white and gray matter. Multivariable analyses were performed, and odds ratios were calculated to compare women with and those without a history of pre-eclampsia, adjusting for potential confounding effects of age, hypertension status at MRI and Fazekas score. Twenty-two formerly pre-eclamptic women (mean age, 37.8 ± 5.4 years) and 13 control women with a history of normotensive pregnancy (mean age, 40.8 ± 5.5 years) were included in the study. The time since the index pregnancy was 6.6 ± 3.2 years in the pre-eclamptic group and 9.0 ± 3.7 years in controls. The leakage rate and fractional leakage volume were significantly higher in formerly pre-eclamptic women than in controls in the global white (P = 0.001) and gray (P = 0.02) matter. Regionally, the frontal (P = 0.04) and parietal (P = 0.009) cortical gray matter, and the frontal (P = 0.001), temporal (P < 0.05) and occipital (P = 0.007) white matter showed higher leakage rates in formerly pre-eclamptic women. The odds of a high leakage rate after pre-eclampsia were generally higher in white-matter regions than in gray-matter regions. This observational study demonstrates global impairment of the BBB years after a pre-eclamptic pregnancy, which could be an early marker of long-term cerebrovascular disorders. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Women with a history of preeclampsia have preserved sensory nerve-mediated dilatation in the cutaneous microvasculature.

What is the central question of this study? Are sensory nerve-mediated vasodilatation and the NO-dependent contribution to that response attenuated in the cutaneous microvasculature of women who have had preeclampsia? What is the main finding and its importance? Women who have had preeclampsia demonstrate attenuated microvascular endothelium-dependent dilatation compared to women with a history of uncomplicated pregnancy. However, there are no differences in sensory nerve-mediated vasodilatation between groups. This suggests that the neurogenic response is not altered following preeclampsia, and that the NO-dependent vasodilatation of the neurogenic response is not related to endothelium-dependent NO-mediated dilatation in these women. Women who have had preeclampsia (PE) demonstrate microvascular endothelial dysfunction, mediated in part by reduced nitric oxide (NO)-dependent mechanisms. Localized heating of the skin induces a biphasic vasodilatation response: a sensory nerve-mediated initial peak, followed by a sustained endothelium-dependent plateau. We have previously shown that the endothelium-dependent plateau is attenuated in PE. However, it is unknown if the sensory nerve-mediated initial peak is similarly attenuated. Therefore, the purpose of this study was to examine the effect of PE history on sensory nerve-mediated vasodilatation and the NO-dependent contribution to that response. We hypothesized that PE would have an attenuated initial peak and a reduced NO-dependent contribution to that response compared to women with a history of normotensive pregnancy (healthy controls, HC). Nine HC (31±4years) and nine PE (28±6years) underwent a standard local heating protocol (42°C; 0.1°Cs-1 ). Two intradermal microdialysis fibres were placed in the skin of the ventral forearm for the continuous local delivery of lactated Ringer solution alone (control) or 15-mM NG -nitro-l-arginine methyl ester for nitric oxide synthase (NOS) inhibition. Red blood cell flux was measured at each site by laser Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated (CVC=LDF/mean arterial pressure) and normalized to maximum (%CVCmax ; 28-mM SNP + local heat 43°C). There were no differences in the initial peak between groups (HC: 79±8 vs. PE: 80±10%CVCmax ; P=0.936). NOS inhibition attenuated the initial peak in both HC (57±18% CVCmax ; P=0.003) and PE (54±10%CVCmax ; P=0.002). However, there were no differences in the NO-dependent portion of the initial peak (HC: 23±16 vs. PE: 24±9%; P=0.777). The local heating plateau (HC: 99±4 vs. PE: 88±7%CVCmax ; P=0.001) and NO contribution to the plateau (HC: 31±9 vs. PE: 17±14%; P=0.02) were attenuated in PE. There was no relation between NO-dependent dilatation in the initial peak and NO-dependent dilatation in the plateau across groups (R2 =0.005; P=0.943). Women who have had PE demonstrate attenuated microvascular endothelium-dependent dilatation. However, there are no differences in sensory nerve-mediated vasodilatation following PE, suggesting that the NO-dependent vasodilatation of the neurogenic response is not related to endothelium-dependent NO-mediated dilatation in these women.

Hypertensive Diseases in Pregnancy and Kidney Function Later in Life: The Genetic Epidemiology Network of Arteriopathy (GENOA) Study

ObjectiveTo evaluate the relationship between hypertensive diseases in pregnancy and kidney function later in life. MethodsWe evaluated measured glomerular filtration rate (mGFR) using iothalamate urinary clearance in 725 women of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Women were classified by self-report as nulliparous (n=62), a history of normotensive pregnancies (n=544), a history of hypertensive pregnancies (n=102), or a history of pre-eclampsia (n=17). We compared adjusted associations among these four groups with mGFR using generalized estimating equations to account for familial clustering. Chronic kidney disease (CKD) was defined as mGFR of less than 60 mL/min per 1.73 m2 or urinary albumin-creatinine ratio (UACR) greater than or equal to 30 mg/g. ResultsAmong women with kidney function measurements (mean age, 59±9 years, 52.9% African American), those with a history of hypertensive pregnancy had lower mGFR (–4.66 ml/min per 1.73 m2; 95% CI, -9.12 to -0.20) compared with women with a history of normotensive pregnancies. Compared with women with a history of normotensive pregnancies, women with a history of hypertensive pregnancy also had higher odds of mGFR less than 60 ml/min per 1.73 m2 (odds ratio, 2.09; 95% CI, 1.21 to 3.60). Additionally, women with a history of hypertensive pregnancy had greater odds for chronic kidney disease (odds ratio, 4.89; 95% CI, 1.55 to 15.44), after adjusting for age, race, education, smoking history, hypertension, body mass index, and diabetes. ConclusionA history of hypertension in pregnancy is an important prognostic risk factor for kidney disease. To our knowledge, this is the first and largest investigation showing the association between hypertensive diseases in pregnancy and subsequent kidney disease using mGFR in a large biracial cohort.

Abstract 052: Hypertensive Diseases In Pregnancy And Hemodynamic Stress Later In Life

Background: Hypertensive diseases in pregnancy have been associated with cardiovascular diseases later in life. However, less is known about the relationship between hypertensive diseases in pregnancy and hemodynamic stress later in life. We evaluated the relationship between hypertensive diseases in pregnancy and plasma levels of biomarkers of hemodynamic stress later in life in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Methods and Results: We investigated 1605 women from the GENOA study (mean age 61±10 years, 57.1% African American).Women were classified as self-reported as nulliparous women (n=140), a history of normotensive pregnancies (n=1,195), a history of a hypertensive pregnancy (n= 229), or a history of preeclampsia (n= 41). We compared adjusted associations among this groups with 4 biomarkers of hemodynamic stress using generalized estimating equations to account for familial clustering. After adjusting for age, race, level of education, smoking history, hypertension, body mass index (BMI), history of coronary artery disease, and diabetes, women with a history of preeclampsia had higher levels of C-terminal proendothelin (CT-proET) compared to women with a history of normotensive pregnancies (Table, p=0.01). There were no significant differences in the levels of midregional proatrial natriuretic peptide (MR-proANP), midregional proadrenomedullin (MR-proADM), and C-Terminal proarginine vasopressin (CT-proAVP) in this groups. Conclusions: Elevated levels of CT-proET (a precursor to the potent vasoconstrictor Endothelin 1) demonstrates a strong relationship among those with a history of preeclampsia. Future studies are warranted to further explore the relationship between CT-proET in the pathogenesis of preeclampsia as well as subsequent changes in cardiovascular structure and function associated with a history of preeclampsia later in life.

Women with a History of Preeclampsia Have Preserved Neurogenically‐Mediated Dilation in the Cutaneous Microvasculature

Women who have had preeclampsia (PrEC) demonstrate microvascular endothelial dysfunction, mediated in part by reduced nitric oxide (NO)-dependent mechanisms. Localized heating of the skin induces a biphasic vasodilation response: a neurogenically-mediated initial peak, followed by a sustained endothelium-dependent plateau. We have previously shown that the endothelium-dependent plateau is attenuated in PrEC, due to attenuated NO-dependent dilation. However, it is unknown if the same is true concerning the neurogenically-mediated initial peak. The purpose of this study was to (1) examine the effect of preeclampsia history on neurogenically-mediated vasodilation and the NO-dependent contribution to that response, and (2) examine the relation between NO-dependent neurogenic dilation and the NO-dependent portion of the endothelium-dependent plateau. We hypothesized that PrEC would have an attenuated initial peak response and a reduced NO-dependent contribution to that response compared to women with a history of normotensive pregnancy (HC). Six HC (31±2yrs, 7±2 months post-partum) and 7 PrEC (29±2yrs, 7±3months post-partum) underwent a standard local heating protocol (42°C; 0.1°C·s-1). Two intradermal microdialysis fibers were placed in the skin of the ventral forearm for the continuous local delivery of Lactated Ringer's alone (control) or 15mM NG-nitro-L-arginine methyl ester (L-NAME) for nitric oxide synthase (NOS)-inhibition. Red blood cell flux was measured at each site via laser-Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated (CVC=LDF/mean arterial pressure) and normalized to maximum (%CVCmax; 28mM SNP + local heat 43°C). NO-dependent dilation was calculated within-subject as the difference between control and NOS-inhibited sites. There were no differences in the initial peak between groups (HC: 80±5 vs PrEC: 79±5 %CVCmax; p=.88). NOS-inhibition attenuated the initial peak in both HC (Control: 80±5 vs L-NAME: 57±9 %CVCmax; p=0.02) and PrEC (Control: 79±5 vs L-NAME: 53±6 %CVCmax; p=0.004). However, there were no group differences in the NO-dependent portion of initial peak (HC: 23±8 vs PrEC: 24±5 %CVCmax; p=0.97). The local heating plateau (HC: 99±2 vs PrEC: 85±1 %CVCmax; p<0.001) and NO-contribution to the plateau (HC: 47±5 vs PrEC: 14±5 %CVCmax; p<0.001) were attenuated in PrEC compared to HC. There was no relation between NO-dependent dilation in the initial peak and NO-dependent dilation in the plateau across groups (R2 = 0.05; p = 0.51). Women who have had preeclampsia demonstrate attenuated microvascular endothelium-dependent dilation compared to women with a history of uncomplicated pregnancy. However, there are no differences in neurogenically-mediated vasodilation between the groups, suggesting that the NO-dependent vasodilation of the neurogenic response is not related to endothelium-dependent NO-mediated dilation in these women.

Maternal myocardial dysfunction after normotensive fetal growth restriction compared with hypertensive pregnancies: a speckle-tracking study.

Pregnancy complicated by preeclampsia and fetal growth restriction (FGR) relates to increased risk of cardiovascular disease later in life, but to different extents. Subclinical cardiac alterations precede eminent cardiovascular disease. Speckle-tracking echocardiography is an elegant method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to evaluate the prevalence of subclinical myocardial dysfunction in former preeclampsia patients (with and without FGR) compared with normotensive women with FGR. For this cross-sectional study, we retrospectively selected women with a history of normotensive FGR (n = 17), preeclampsia with FGR (n = 26) and preeclampsia without FGR (n = 134) who underwent conventional echocardiography as part of the clinical cardiovascular work-up after complicated pregnancies between 6 months and 4 years postpartum in Maastricht, The Netherlands. We excluded women with chronic hypertension, hypercholesterolemia and obesity. Women with normotensive FGR showed subclinical left ventricular (LV) impairment in systodiastolic function with concentric remodeling, slight alteration in right ventricular systolic function and left atrial strain, similarly to the preeclampsia group independently from the fetal growth. LV hypertrophy was only present in about 10% of cases who experienced preeclampsia (independently from the fetal growth) but not in those with normotensive FGR. Similar to women with a history preeclampsia, women with a history of normotensive pregnancy but with FGR have abnormal myocardial function, shown with speckle-tracking echocardiography. Therefore, both preeclampsia and normotensive FGR should be viewed upon as risk indicator for subclinical myocardial impairment that may benefit from cardiovascular risk management.

Hypertensive diseases in pregnancy, cardiac structure and function later in life: Insights from the Genetic Epidemiology Network of Arteriopathy (GENOA) study.

Hypertensive diseases in pregnancy have been associated with altered cardiac structure and function, yet these associations have not been systematically investigated in larger populations including African Americans. We evaluated the relationships between hypertensive diseases in pregnancy with cardiac structure and function later in life in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We investigated 1013 African American women sibships with echocardiographic measurements from the GENOA study (Phase II, 2000-05; Jackson, MS). Women were classified as self-reported nulliparous (n=61), a history of normotensive pregnancies (n=780), a history of a hypertensive pregnancies (n=152), or a history of preeclampsia (n=20). We compared adjusted associations among these 4 groups with echocardiographic measurements of cardiac structure and function using generalized estimating equations, accounting for familial clustering. Among 1013 women with echocardiographic data (mean age 62±9.5years), women with a history of hypertensive pregnancy had lower left ventricular ejection fraction (LVEF) (P=0.043) compared to nulliparous women and higher left atrial systolic dimension (LASD) compared to women with a history of normotensive pregnancies (P=0.010), After adjusting for cardiovascular risk factors. There were no statistically significant differences in other echocardiographic parameters among these groups. A history of hypertension in pregnancy is associated with lower LVEF later in life, compared to nulliparous women and higher LASD compared to women with a history of normotensive pregnancies. However, given the multiple comparisons considered, this finding should be interpreted cautiously and requires further study.

210. Reduced barrier function of the microvascular endothelial glycocalyx in women with a history of preeclampsia, one year after delivery

Introduction The endothelial glycocalyx is a proteoglycan- and glycoprotein-rich layer at the interface of the flowing blood and the cell membrane. It regulates key endothelial functions and is critical for vascular health. The effects of glycocalyx damage (e.g., proteinuria, pro-coagulation, inflammation, vasospasm) suggest that the glycocalyx might have an important role in the pathophysiology of preeclampsia and increased risk of later life cardiovascular disease in these women. Hypothesis We hypothesized that, 1 year after delivery, non-pregnant women with a history of preeclampsia evidence microvascular glycocalyx damage compared to non-pregnant controls who had a normotensive, uncomplicated pregnancy. Methods Glycocalyx damage was assessed using sidestream dark field imaging and was defined as deeper penetration of RBCs into the glycocalyx of the sublingual microcirculation (5–25 μm diameter). Twenty-one women with a history of normotensive pregnancy (NP) and 10 women with prior preeclampsia (PE) were examined at one year after delivery. We compared movement of RBCs into the glycocalyx (perfused boundary region, PBR), microvascular density (total length of perfused microvessels/mm2), and RBC filling percentage (percentage of time in which vascular segments are perfused). Results Glycocalyx PBR was significantly increased in women with prior PE compared to NP (2.32 ± 0.22 μm PE vs. 2.1 ± 0.22 μm NP, P Discussion One year after delivery, the sublingual microvacular glycocalyx is functionally damaged in women with prior preeclampsia as indicated by an increase in PBR (magnitude similar to end-stage renal disease). There is also evidence of impaired microvascular perfusion. Glycocalyx degradation may contribute to increased risk of later life cardiovascular disease in women with a history of preeclampsia. Funded by NIH-NICHD (P01 HD030367, R21 HD083659), and AHA 16SFRN27870000.

Clinical Implications

HomeHypertensionVol. 71, No. 1Clinical Implications Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBClinical Implications Originally published1 Jan 2018https://doi.org/10.1161/HYPERTENSIONAHA.117.10603Hypertension. 2018;71:2Hypertensive Phenotypes After Preeclampsia (p 103)Download figureDownload PowerPointPreeclampsia is associated with a greater lifetime risk for cardiovascular and renal complications. International guidelines underline that women with hypertensive disorders of pregnancy should benefit from a postpartum screening and management of cardiovascular risk factors. However, specific recommendations, especially on the timing of the first medical visit and tests that need to be done, are still lacking. In this study, we performed ambulatory blood pressure monitoring 6 to 12 weeks after delivery in women who had preeclampsia and women who had not (controls). We found that preeclampsia was associated with a higher prevalence of diurnal and nocturnal ambulatory hypertension. Among women with preeclampsia, half of them were still hypertensive in the postpartum, with an increased prevalence of white coat and masked hypertension. They also had an abnormal circadian rhythm with a significant proportion of reversed rhythm. The index of salt-sensitivity risk, calculated from ambulatory blood pressure monitoring parameters, was significantly increased after preeclampsia. Individually, and in the general population, these hypertensive phenotypes are associated with a higher risk for cardiovascular disease later in life. Whether they are contributing factors or a consequence of preeclampsia is not known. Ambulatory blood pressure monitoring after preeclampsia is useful and helps to identify high-risk women. Early lifestyle modifications and regular medical follow-up should be offered to these women. The impact of these measures on future cardiovascular events remains of course to be determined in prospective trials.Myeloid-Derived Suppressor Cells, Cyclo sporine A, and Hypertension (p 199)Download figureDownload PowerPointCyclosporine A (CsA) is prescribed to reduce focal segmental glomerulosclerosis, membranous nephropathy, psoriasis, rheumatoid arthritis, and other autoimmune diseases despite the known prohypertensive side effect. Until new immunosuppressive drugs for these disorders are developed and used routinely in patients, strategies to blunt the negative cardiovascular and renal effects of CsA are needed. We demonstrate that augmenting a particular regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is able to eradicate the hypertension, endothelial dysfunction, and vascular and glomerular injury caused by CsA in mice. The protective effects of increased MDSC levels caused by both interleukin-33 treatment and adoptive transfer of MDSCs demonstrate that CsA toxicity can be prevented and reversed. Beneficial effects of MDSCs have been reported in other forms of experimental hypertension and in various inflammatory and autoimmune diseases; therefore, autologous cell therapy with MDSCs may be feasible soon. Groups are generating MDSCs from various cells, including mouse embryonic stem cells and hematopoietic stem cells, as well as human peripheral blood mononuclear cells. Given the strong antihypertensive and organ-protective effects, MDSC therapy should be tested in patients being treated with CsA.Pregnancy History and Cerebrovascular Reactivity (p 110)Download figureDownload PowerPointHypertension during pregnancy is associated with an increased risk of developing cardiovascular or cerebrovascular disease later in life. Our group has shown that postmenopausal women who have experienced preeclampsia have lower brain volume and cognitive scores compared with women who had a normotensive pregnancy. The mechanisms underlying the interaction between pregnancy history and brain structure and function have not been elucidated. Because pregnancy-related changes in the circulation may contribute to pathological changes in the brain, we investigated cerebral blood flow reactivity and markers of vascular activation in women with a history of preeclampsia. In this study in Hypertension, women who either had a normotensive or preeclamptic pregnancy between 1976 and 1982 were recruited ≈35 years after the pregnancy. Women with a history of preeclampsia had lower cerebral blood flow velocity and reduced cerebrovascular reactivity, indicating cerebral microvascular dysfunction, compared with women with a history of normotensive pregnancy. Additionally, procoagulant circulating blood elements were associated with cerebral hemodynamic variables only in women with history of preeclampsia. Collectively, these results suggest that differences in circulating vasoactive factors in women with a history of preeclampsia might affect the reactivity of the cerebral circulation years beyond the preeclamptic pregnancy. These differences may contribute to brain atrophy and increased risk of cognitive decline in women with a history of preeclampsia. Previous Back to top Next FiguresReferencesRelatedDetails January 2018Vol 71, Issue 1 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.117.10603 Originally publishedJanuary 1, 2018 PDF download Advertisement

Influence of preeclampsia and late-life hypertension on MRI measures of cortical atrophy.

Women with a history of preeclampsia are at an increased risk of hypertension and structural brain changes. However, the combined effect of both preeclampsia and late-life hypertension on brain structural changes is not known and was investigated in this study. Participants were identified from the population-based Rochester Epidemiology Project cohort. Four groups of women were recruited and investigated in this study: first, women with a history of normotensive pregnancy who have late-life hypertension (n = 8, median age = 62), second, women with a history of normotensive pregnancy who do not have late-life hypertension (n = 32, median age = 59), third, women with a history of preeclampsia who have late-life hypertension (n = 24, median age = 60), and fourth, women with a history of preeclampsia who do not have late-life hypertension (n = 16, median age = 57). Cerebrovascular disease lesions on MRI, and total gray matter volumes were assessed. Total gray matter volumes were smaller in women with a history of preeclampsia and late-life hypertension compared with the other groups. Voxel-based morphometry demonstrated that the volume changes were localized to the posterior brain regions, particularly the occipital lobe gray matter in women with a history of preeclampsia and late-life hypertension. Having late-life hypertension superimposed on a history of preeclampsia affects the brain structure differently than having either a history of preeclampsia alone or a history of normotensive pregnancy either with or without late-life hypertension.

Preeclampsia and cognitive impairment later in life

Hypertension is a risk factor for cerebrovascular disease and cognitive impairment. Women with hypertensive episodes during pregnancy report variable neurocognitive changes within the first decade following the affected pregnancy. However, long-term follow-up of these women into their postmenopausal years has not been conducted. The aim of this study was to examine whether women with a history of preeclampsia were at increased risk of cognitive decline 35-40 years after the affected pregnancy. Women were identified and recruited through the medical linkage, population-based Rochester Epidemiologic Project. Forty women with a history of preeclampsia were age- and parity-matched to 40 women with a history of normotensive pregnancy. All women underwent comprehensive neuropsychological assessment and completed self-report inventories measuring mood, ie, depression, anxiety, and other symptoms related to emotional state. Scores were compared between groups. In addition, individual cognitive scores were examined by neuropsychologists and a neurologist blinded to pregnancy status, and a clinical consensus diagnosis of normal, mild cognitive impairment, or dementia for each participant was conferred. Age at time of consent did not differ between preeclampsia (59.2 [range 50.9-71.5] years) and normotensive (59.6 [range 52.1-72.2] years) groups, nor did time from index pregnancy (34.9 [range 32.0-47.2] vs 34.5 [range 32.0-46.4] years, respectively). There were no statistically significant differences in raw scores on tests of cognition and mood between women with histories of preeclampsia compared to women with histories of normotensive pregnancy. However, a consensus diagnosis of mild cognitive impairment or dementia trended toward greater frequency in women with histories of preeclampsia compared to those with normotensive pregnancies (20% vs 8%, P= .10) and affected more domains among the preeclampsia group (P= .03), most strongly related to executive dysfunction (d= 1.96) and verbal list learning impairment (d= 1.93). These findings suggest a trend for women with a history of preeclampsia to exhibit more cognitive impairment later in life than those with a history of normotensive pregnancy. Furthermore, the pattern of cognitive changes is consistent with that observed with vascular disease/white matter pathology.

Sympathetic responsiveness is not increased in women with a history of hypertensive pregnancy.

Hypertensive pregnancy (HTNP) is a risk factor for future cardiovascular disease. Exaggerated cardiovascular responses to physical stress are also considered an independent marker of cardiovascular disease risk. However, there are limited data regarding the blood pressure (BP) responses to acute stress in women, who have a history of HTNP. Hence, the aim of the study is to compare BP responses to a physical stress in postmenopausal women with a history of HTNP to age- and parity-matched women with a history of normotensive pregnancy (NP). Beat-to-beat BP and heart rate was recorded in 64 postmenopausal women with [age = 58.5 (55.2, 62.2) yr, where values are the median, 25th percentile, and 75th percentile] and without [age = 59.4 (55.9, 62.4) yr] a history of HTNP before and during isometric handgrip (IHG) exercise (30% of maximal voluntary contraction) to fatigue. Muscle metaboreflex was measured during postexercise ischemia following IHG exercise. BP variables increased similarly in response to IHG exercise [systolic: NP = 11.5 (8.9, 17.6) %, HTNP = 11.3 (9.5, 15.9) %; diastolic NP = 11.2 (7.9, 13.3) %, HTNP = 9.5 (7.1, 14.3) %; mean blood pressure: NP = 9.8 (5.0, 13.6) %, and HTNP = 7.2 (4.4, 10.4) %] and postexercise ischemia [systolic: NP = 14.1 (10.3, 23.0) %, HTNP = 15.8 (10.6, 21.4) %; diastolic NP = 12.2 (4.8, 17.0) %, HTNP = 10.4 (5.3, 17.1) %; and mean blood pressure: NP = 11.1 (6.1, 17.9) %, HTNP = 9.4 (2.9, 14.8) %] in both groups. Although having a history of HTNP is associated with future cardiovascular disease risk, results from this study suggest that the risk may not be manifested through altered cardiovascular metaboreflex response to physical stressors.

Preeclampsia and cardiovascular disease risk assessment - Do arterial stiffness and atherosclerosis uncover increased risk ten years after delivery?

Epidemiological studies associate preeclampsia with increased risk of premature cardiovascular disease (CVD) later in life. This study aims to make a comprehensive CVD risk assessment comparing women with previous preeclamptic pregnancies to women with previous normotensive pregnancies 10years after index pregnancy. A nested, matched, observational cohort study. Markers of arterial stiffness, aortic pulse wave velocity (aPWV) and augmentation index (AIx-75), and markers of atherosclerosis, carotid intima-media thickness (cIMT) and carotid plaque presence. Traditional CVD risk factors and 10-year and 30-year Framingham CVD risk scores were also assessed. Women were included from April 2014 to October 2014 at a tertiary referral hospital in Denmark. Twenty-one exposed women with a history of preeclampsia and 21 unexposed with a history of normotensive pregnancies were included. Ten years after delivery, significantly more exposed women suffered from hypertension and received antihypertensive treatment and significantly more fulfilled the hypertension-definition at screening. Previously preeclamptic women also tended to have more unfavorable CVD risk estimates. The Framingham risk scores seemed to extend the unfavorable CVD risk. The exposed women tended to have a higher aPWV compared to unexposed women, (P=0.057). No differences were shown in the other examined arteriosclerotic or atherosclerotic variables. Ten years after delivery, we found increased risk of hypertension and trend toward unfavorable CVD risk profile in 40-year-old previously preeclamptic women. However, arterial stiffness and atherosclerosis did not uncover any additional CVD risk information at this time point.

Assessment of endothelial function by flow-mediated dilation of the brachial artery in adolescents with a history of preeclampsia or a normotensive pregnancy

Objectives: to determine the prevalence of endothelial dysfunction and its association with a history of mild and severe preeclampsia in adolescents. Methods: a cross-sectional study was carried out at the MEAC-UFC with 103 primiparous adolescents postpartum. The assessment of endothelial function was performed by way of flow-mediated dilatation of the brachial artery. Variables (age, body mass index, gestational age at delivery, systolic and diastolic blood pressure and flow-mediated dilation) were compared between groups. p&lt;0.05 was considered to be statistically significant. Results: twenty-four (23.3%) patients had preeclampsia (PE): 11 mild and 13 severe. The overall prevalence of endothelial dysfunction was 23.3% (21.5% of patients with normotensive pregnancies and 29.2% of the PE patients: 18.2% of those with mild PE and 38.5% of those with severe PE). The figures were statistically significant for systolic blood pressure, p=0.007. Conclusions: patients with a history of PE have higher systolic blood pressure than patients with a history of normotensive pregnancy, but did not have more endothelial dysfunction.

Hypertension in pregnancy is associated with elevated C-reactive protein levels later in life

We assessed whether hypertension in pregnancy is associated with elevated C-reactive protein (CRP) levels in later life, possibly reflecting an increased risk of cardiovascular disease (CVD). Elevated CRP levels have been associated with hypertension in pregnancy and with CVD. We studied 2463 women from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Participants were categorized as nulliparous women (n = 219), women with a history of normotensive pregnancies (n = 1839), or women with a history of a hypertensive pregnancy (n = 405). Using multiple linear regression models, we compared mean CRP levels among the groups after adjusting for age, race, education, smoking, hypertension, personal history of coronary heart disease (CHD) or stroke, diabetes, dyslipidemia, statins, hormone replacement therapy, and family history of CHD or stroke. As CRP levels may be influenced by BMI, the model was fit both with and without adjusting for BMI. There was no significant difference in CRP levels between nulliparous women and those with a history of normotensive pregnancies, either with (P = 0.82) or without (P = 0.46) adjusting for BMI. In contrast, women with hypertensive pregnancies, compared with those with normotensive pregnancies, had higher CRP levels, both with (P = 0.009) and without (P < 0.001) adjusting for BMI. A history of hypertension in pregnancy is associated with elevated CRP levels later in life, independent of traditional CVD risk factors and BMI. An elevated CRP may reflect an inflammatory state in women with a history of hypertensive pregnancy disorders who are at increased risk for CVD.