History Of Early-onset Preeclampsia Research Articles

The Risk of Persistent Hypertension and Chronic Kidney Disease in Early- and Late-Onset Preeclampsia: A Report From Developing Country.

Preeclampsia (PE) has been disproportionately prevalent in developing countries and constitutes a leading cause of maternal mortality, and also has long-term impacts, including renal consequences.This study aimed to explore the risk of persistent hypertension and kidney failure in early-onset PE (EOP) and late-onset PE (LOP) in the five years after delivery. This retrospective cohort study included women with a prior history of severe PEor normotensive pregnancy admitted to tertiary hospitals in Indonesia. The blood pressure, body mass index (BMI), urea, creatinine serum, and protein urine were analyzed, and the risk of chronic kidney disease (CKD) after five years was performed using theKidney Disease Improvement Global Outcomes (KDIGO) classification. Twenty-seven EOP, 35 LOP, and 30 normotensive cases were included. Mean blood pressure after five years was recorded as 115.6 ± 14.25 mmHg in the normotensive group, 131.82 ± 19.34 mmHg in the LOP group, and 154.96 ± 23.48 mmHg in the EOP group. According to the KDIGO classification, the normotensive group had an average 10% risk of CKD, but severe PE had a risk of CKD greater than 90%. In the severe PE group, the risk of CKD was 20.94 times higher compared to normotensive women (OR 20.94; 95% CI 2.67-163.72, p = 0.004). The risk of CKD in the EOP group was 6.75 times higher than in the LOP group (OR 6.75; 95% CI 2.19-20.76, p = 0.001), whereas persistent hypertension in the EOP group was 5.78 times higher than in the LOP group (OR 5.78; 95% CI 1.91-17.395, p = 0.002). PE women have a higher risk of CKD than normotensive women. Women with a history of EOP are more likely to develop persistent hypertension and CKD than women with a prior LOP history.

Cardiovascular profiles associated with white matter hyperintensities in healthy young women.

Women who experience hypertension in pregnancy have increased risk of both chronic hypertension and dementia. High blood pressure is associated with increased evidence of white matter hyperintensities (WMH) in brain imaging. WMH are disruptions of the white matter of the brain that occur with demyelination and axonal degeneration, are associated with vascular disease, occur more frequently in people with hypertension, and are associated with cognitive impairment. We evaluated the relationship between WMH and subclinical cardiovascular function in healthy young nulliparous women and women with a history of early-onset preeclampsia. Sixty-two reproductive-aged women were assessed during the follicular phase of the menstrual cycle after a 3-day sodium/potassium-controlled diet. Half of participants had a history of early-onset preeclampsia, and half were nulliparous. Blood was drawn to assess inflammatory markers. Cardiovascular assessments included tonometric blood pressure monitoring, volume loading to assess vascular compliance, echocardiography to assess cardiac ejection time, brachial pulse wave velocity of the brachial artery, assessing cardiovascular stiffness, and brachial artery flow mediated vasodilation to assess endothelial mediated dilatory response. T2 fluid-attenuated inversion recovery (FLAIR) MRI imaging was obtained. Two raters, blinded to cardiovascular assessments and pregnancy history, reviewed MRI scans for evidence of WMH using the Fazekas rating scale. WMHs were detected in 17 women; 45 had normal white matter structure. Participants with Fazekas score>0 had exaggerated response to volume loading compared to women with a Fazekas score of 0 and longer cardiac ejection times. Fazekas scores >0 had lower brachial flow-mediated vasodilation and increased white blood count compared to those with no evidence of WMH. Women with WMH had reduced cardiovascular compliance, and a trend towards decreased endothelial responsiveness compared to those without WMH. These data demonstrated that the relationship between cardiovascular and brain health was detectable in young, healthy, reproductive-aged women, and may play a role in later development of clinical disease. These findings may help identify women who are at risk for cognitive decline and pathological aging.

THE CHANGES OF RENAL FUNCTION STATUS BASED ON PROTEINURIA AND GLOMERULUS FILTRATION RATE IN PATIENTS WITH HISTORY OF PREECLAMPSIA WITH SEVERE FEATURES

Background: Preeclampsia with severe features is an endothelial disease that causes renal system disorders during pregnancy. Preeclampsia is an important cause of acute kidney injury and risk for chronic kidney disease. Methods: This study was a case series conducted at the Department of Obstetrics and Gynecology, H. Adam Malik General Hospital Medan, Indonesia starting from December 2019 until January 2020. Total sampling technique was employed obtaining 31 subjects with a history of preeclampsia with severe features for at least 3 months to 2 years postpartum, without a history of chronic disease, diabetes mellitus, and congenital kidney disorders. Proteinuria, serum creatinine, and GFR calculations were performed. Results: There were 31 patients who met the inclusion and exclusion criteria. At a time interval of 4 - ≤13 months postpartum, 2 levels of proteinuria +1 (0-2), serum creatinine 0.81 ± 0.21 mg/dl, and levels of GFR 109.57 ± 25.13 (ml/min/1.73 m ). Whereas at the time interval of >13 - 24 months postpartum, levels of proteinuria +1 (0-3), serum creatinine 0.85 ± 0.23 mg/dl, and GFR 2 levels of 104. 41 ± 28.45 (ml/min/1.73 m ). The mean of serum creatinine before delivery was 0.69 ± 0.15 mg/dl and after delivery was 0.83 ± 0.22 mg/dl. The mean of GFR postpartum at group of history of early onset preeclampsia was 103.07 ± 25.23 2 2 (ml/min/1.73 m ) and group of history of late onset preeclampsia was 113.40 ± 28.24 (ml/min/1.73 m ). Conclusion: There was a tendency for a decrease in renal function among women with a history of preeclampsia with severe features with ndings of persistent proteinuria from more than 3 to 24 months postpartum, an increase in mean of serum creatinine levels from before and after delivery and a decrease in GFR, but it was not signicant. This was related to the slow course of chronic kidney disease, so it had to be followed up periodically.

Association of maternal angiotensin II type 1 and type 2 receptor combination genotypes with susceptibility to early-onset preeclampsia.

Allelic variations affecting the activity of the maternal renin-angiotensin system may play a role in the development of hypertensive disorders of pregnancy like preeclampsia, its more severe early-onset form, and intrauterine growth restriction. We examined the association of common allelic variants of angiotensin II type 1 and type 2 receptor genes (AT1R and AT2R) sorted in five AT1R/AT2R receptor combination genotype groups with susceptibility to early-onset preeclampsia (EOP). The occurrence of AT1R (A1166C) and A2TR (C3123A) alleles in wild type (AA, CC), heterozygous (A/C, C/A), and homozygous (C/C, A/A) states was recorded in 84 women with a history of EOP and 84 age-matched controls sorted in five AT1R/AT2R receptor combination genotype (wild type: AA/CC, one mutant: AA/CA, AC/CC, two mutant: AC/CA, AA/AA, CC/CC, three mutants: AC/AA, CC/CA and four mutant: CC/AA) groups, by polymerase chain reaction-RFLP analysis. Three mutant receptor combination genotype carriers were more common in women with a history of EOP than in controls (26.18% vs. 4.76%, p = 0.003, OR = 8.25). Receptor combination genotyping may be of clinical value in: (a) maternal prediction of susceptibility to EOP, (b) disease subtyping for directed studies with receptor signaling antagonists, (c) the broader study of hypertension.

Effects of low-molecular-weight heparin and aspirin in recurrent pre-eclampsia: A stratified cohort study.

To evaluate the effects of low-molecular-weight heparin (LMWH) combined with low-dose aspirin (LDA) in pregnant women with a history of pregnancy-related hypertensive disorders. In the current retrospective stratified cohort study, 33 women with previous hypertensive disorders of pregnancy treated with LMWH and LDA were compared with 37 control women who did not undergo LMWH or LDA treatment. Rates of pre-eclampsia recurrence, placental abruption, and other adverse outcomes for the fetuses and pregnant women were compared in the two groups. The pre-eclampsia recurrence rates were 12/33 (36.4%) in the LMWH+LDA group and 28/37 (75.7%) in the control group (P<0.01). In stratified cohort analysis, pregnant women with a history of early-onset pre-eclampsia, a body mass index of at least 24 (calculated as weight in kilograms divided by the square of height in meters), and aged less than 35years benefited from LMWH+LDA treatment. In women with chronic hypertension or a history of placental abruption there was no protective effect. There were no significant differences in other adverse outcomes such as placental abruption and small size for gestational age in fetuses or pregnant women in the two groups. Administration of LMWH+LDA only lowered the risk of pre-eclampsia recurrence in subgroups of pregnant women with a history of pregnancy-associated hypertensive disorders.

High-sensitivity cardiac troponin I in women with a history of early-onset preeclampsia.

Preeclampsia is associated with an elevated risk of cardiovascular disease later in life. Women with a history of preeclampsia are at risk of developing hypertension as well as ischemic heart disease. Identification of women at the highest risk is important to initiate preventive strategies. We investigated whether high-sensitivity cardiac troponin I (hs-cTnI) levels are associated with a history of early-onset preeclampsia, and with hypertension in these high-risk women. Approximately 9-10 years after pregnancy, hs-cTnI levels were measured for 339 women of the Preeclampsia Risk Evaluation in FEMales cohort, consisting of 177 women with a history of early-onset preeclampsia and 162 women with a previous uncomplicated index pregnancy. Associations were analyzed using several statistical tests and linear regression analysis. The median hs-cTnI levels (IQR) were 2.50 ng/l (2.30) in women with a history of early-onset preeclampsia and 2.35 ng/l (2.50) in women without a history of preeclampsia, P = 0.53. Among women with a history of early-onset preeclampsia, the hs-cTnI levels were higher in women who were hypertensive compared with their normotensive counterparts (medians 2.60 versus 2.30; P = 0.03). In addition, blood pressure levels increased with increasing hs-cTnI levels. We did not find a difference in hs-cTnI levels between women with and without a history of early-onset preeclampsia. Nonetheless, hs-cTnI levels were statistically significantly higher in current hypertensive women with a history of preeclampsia compared with their normotensive counterparts. Therefore, hs-cTnI levels might improve risk prediction for women at the highest risk of cardiovascular disease.

A Pilot Randomized Trial Comparing the Effects of 80 versus 160 mg of Aspirin on Midtrimester Uterine Artery Pulsatility Index in Women with a History of Preeclampsia.

To compare the effects of 80 mg and 160 mg of aspirin, initiated in the first trimester of pregnancy, on mid-trimester uterine artery pulsatility index (UtA-PI) in women with a history of preeclampsia. We performed a pilot double-blind randomized controlled trial. Pregnant women with a history of preeclampsia were recruited between 100/7 and 136/7 weeks gestation and randomly assigned to take either 80 or 160 mg of aspirin daily at bedtime from randomization to 356/7 weeks gestation. The primary outcome was mean UtA-PI at 22-24 weeks. Secondary outcomes included the rate of fetal growth restriction and preeclampsia, stratified as term (≥37 weeks), preterm (<37 weeks), and early-onset (<34 weeks) preeclampsia. A total of 107 participants were randomized, including 41 (38%) with a history of preterm preeclampsia and 16 (15%) with a history of early-onset preeclampsia. We observed no significant difference in mean UtA-PI at 22-24 weeks between the 2 groups (0.97; 95% CI 0.88-1.05 vs. 0.97; 95% CI 0.88-1.07, P = 0.9). The rates of fetal growth restriction (8% vs. 2%; P = 0.20); preeclampsia (12% vs. 15%; P = 0.78), preterm preeclampsia (4% vs. 2%; P = 0.56), and early-onset preeclampsia (0% vs. 2%; P = 0.52) were similar in both groups. No serious adverse events associated with the study treatment were reported. We observed no significant difference in UtA-PI between the two doses of aspirin, but we observed low rates of fetal growth restriction and preterm and early-onset preeclampsia (all less than 5%). The benefits of aspirin for the prevention of preterm preeclampsia is probably not related to the improvement of deep placentation alone.

Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia.

Introduction: Preeclampsia (PE) represents a hypertensive pregnancy disorder that is associated with increased cardiovascular disease (CVD) risk. This increased risk has been attributed to accelerated atherosclerosis, with inflammation being a major contributor. Neutrophils play an important role in the onset and progression of atherosclerosis and have been associated with vascular damage in the placenta as well as the chronic inflammatory state in women with PE. We therefore investigated whether circulating neutrophil numbers or reactivity were associated with the presence and severity of subclinical atherosclerosis in women with a history of PE. Methods: Women aged 45–60 years with a 10 to 20 years earlier history of early onset preeclampsia (delivery <34 weeks of gestation) (n = 90), but without symptomatic CVD burden were screened for the presence of subclinical coronary artery disease (CAD) using both contrast-enhanced and non-contrast coronary CT angiography. Subclinical CAD was defined as a coronary artery calcium (CAC) score ≥100 Agatston Units and/or ≥50% coronary luminal stenosis. We assessed whether the numbers and activity of circulating neutrophils were associated with the presence of subclinical CAD and as secondary outcome measurements, with the presence of any calcium (CAC score > 0 AU) or stenosis, categorized as absent (0%), minimal to mild (>0 and <50%), and moderate to severe (≥50%) narrowing of the coronary artery. Blood was drawn just before CT and neutrophil numbers were assessed by flow cytometry. In addition, the presence of the chemokine receptors CXCR2 and CXCR4, which are known to be instrumental in neutrophil recruitment, and neutrophil activity upon stimulation with the bacterial peptide N-Formylmethionyl-leucyl-phenylalanine (fMLF) was assessed by flow cytometry. Results: Of the participating women, with an average age of 49 years, 13% (12 out of 90) presented with subclinical signs of CAD (CAC score ≥100 AU and/or ≥50% luminal stenosis), and 37% (33 out of 90) had a positive CAC score (>0). Total white blood cell count and neutrophil counts were not associated with the presence of subclinical CAD or with a positive CAC score. When assessing the presence of the chemokine receptors CXCR4 and CXCR2, we observed a slight decrease of neutrophil CXCR2 expression in women with CAC (median MFI 22.0 [interquartile range (IQR) 20.2–23.8]) compared to women without CAC (23.8 [IQR 21.6–25.6], p = 0.02). We observed no differences regarding neutrophil CXCR4 expression. In addition, expression of the early activity marker CD35 was slightly lower on neutrophils of women with subclinical CAD (median MFI 1.6 [IQR 1.5–1.9] compared to 1.9 [IQR 1.7–2.1] in women without CAD, p = 0.02). However, for all findings, statistical significance disappeared after adjustment for multiple testing. Conclusion: Our findings indicate that neutrophil counts and (re)activity are not directly associated with silent CAD disease burden and as such are not suitable as biomarkers to predict the presence of subclinical CAD in a high-risk population of women with a history of preeclampsia.

Regulatory antibodies against GPCR in women ten years after early-onset preeclampsia.

Preeclampsia is associated with an increased cardiovascular risk later in life. Anti-GPCR autoantibodies have been shown to contribute to the development of cardiovascular disease. We investigated whether anti-GPCR autoantibodies are elevated in women with a history of early-onset preeclampsia 8-11 years postpartum, and whether they correlate with clinical outcomes. We investigated data from the Preeclampsia Risk EValuation in FEMales cohort, a retrospective matched case-control study. Anti AT1R-, beta1AR-, ETAR-, PAR1- and CXCR3- autoantibodies were determined in 485 samples by using commercially available ELISA. Women with the lowest combined levels of autoantibodies and a history of early preeclampsia had significantly higher SBP, DBP and MAP (all p<0.001) compared to the controls. The individual titer levels of autoantibodies were not different between controls and former early PE groups 8-11 years postpartum. In conclusion, regulatory autoantibodies alone are not sufficient to explain hypertension or other cardiovascular pathologic conditions, but together with other risk factors such as a previous hypertensive pregnancy, lower levels of autoantibodies are associated with increased blood pressure.

Creatine kinase and blood pressure in women with a history of early-onset preeclampsia.

High plasma creatine kinase (CK) activity is associated with hypertension in the general and pregnant population. We hypothesize that women with a history of early-onset preeclampsia are prone to hypertension due to a high CK activity level. Nine to 16 years after pregnancy, serum CK activity and blood pressure were measured in 117 women with a history of early-onset preeclampsia and 50 women with a history of an uncomplicated pregnancy. CK activity levels of the two groups were compared using the Mann-Whitney U test. The association between CK activity and blood pressure was evaluated by means of multivariable regression analysis. There was no significant difference in median (interquartile range) CK activity between women with a history of early-onset preeclampsia and an uncomplicated pregnancy (59.00 [47.00-85.00] vs. 58.00 [46.50-75.25], respectively, p = 0.774). The association between CK and systolic blood pressure was significant in women with a pregnancy history of early-onset preeclampsia (regression coefficient [95% confidence interval]: 0.123 mmHg [0.020-0.226], p = 0.019), and a trend was found for diastolic blood pressure (p = 0.069). CK and blood pressure were not significantly associated in women with a history of an uncomplicated pregnancy. Median CK did not significantly differ between the two groups. Serum CK activity was significantly associated with systolic blood pressure in women with a history of early-onset preeclampsia. These data suggest that CK is not a predominant factor in the increased risk of hypertension in women with a history of early-onset preeclampsia.

146. Regulatory (auto-) antibodies against G-coupled receptors in women ten years after early-onset preeclampsia: Results from the PREVFEM study

Introduction Preeclampsia (PE) is associated with an increased cardiovascular risk in later life, especially in women after early-onset PE. We and others have shown that activating antibodies against angiotensin II receptor type 1 (AT1-) are present in women with PE, even after pregnancy. Further, regulatory (auto-) antibodies against G-coupled receptors (GPCR) have been shown to contribute to cardiovascular disease. Hypothesis We tested the hypothesis that regulatory autoantibodies’ titers are elevated in women with a history of early-onset PE and correlate to physiological parameters and clinical outcomes. Methods We investigated data from PREVFEM (Preeclampsia Risk EValuation in FEMales) retrospective matched case-control study, which was performed in Zwolle, The Netherlands, from 2008 until 2010. All women registered in the early PE database as well as an equal number of age-matched females without PE from the regular obstetric database in the same time period (1991–2007) were invited to participate in the PREVFEM study. Autoantibodies against AT1-, β1-adrenergic receptors, endothelin I receptor A (ETAR), protease-activated receptor 1 (PAR1) and C-X-C3 chemokine binding receptors (CXC3R) were determined in 609 samples (306 cases and 303 controls) by using commercially available ELISA (Celltrend, Luckenwalde, Germany). Results The titer levels of AT1-, β1-, ETAR-, PAR1- and CXC3R-autoantibodies were not significantly different between control and former PE groups 10 years after index pregnancy. Former PE women showed a significantly higher prevalence of hypertension (43% vs. 17%, p Discussion Regulatory autoantibodies against GPCR do not identify women at higher risk for cardiovascular disease 10 years after early-onset PE. The need to search for biomarkers identifying women at risk before cardiovascular symptoms is continuing.

8. Maternal recall of a history of early-onset preeclampsia, late-onset preeclampsia or gestational hypertension: a questionnaire study

Objective: This study assessed women’s ability to recall different types of hypertensive disorders of pregnancy because of its disproportionate cardiovascular risk later in life. Methods: Participa...

ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy.

Low-dose aspirin has been used during pregnancy, most commonly to prevent or delay the onset of preeclampsia. The American College of Obstetricians and Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia. The U.S. Preventive Services Task Force published a similar guideline, although the list of indications for low-dose aspirin use was more expansive. Daily low-dose aspirin use in pregnancy is considered safe and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia. Women at risk of preeclampsia are defined based on the presence of one or more high-risk factors (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic hypertension) or more than one of several moderate-risk factors (first pregnancy, maternal age of 35 years or older, a body mass index greater than 30, family history of preeclampsia, sociodemographic characteristics, and personal history factors). In the absence of high risk factors for preeclampsia, current evidence does not support the use of prophylactic low-dose aspirin for the prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.

ACOG Committee Opinion No. 743 Summary: Low-Dose Aspirin Use During Pregnancy.

Low-dose aspirin has been used during pregnancy, most commonly to prevent or delay the onset of preeclampsia. The American College of Obstetricians and Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia. The U.S. Preventive Services Task Force published a similar guideline, although the list of indications for low-dose aspirin use was more expansive. Daily low-dose aspirin use in pregnancy is considered safe and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia. Women at risk of preeclampsia are defined based on the presence of one or more high-risk factors (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic hypertension) or more than one of several moderate-risk factors (first pregnancy, maternal age of 35 years or older, a body mass index greater than 30, family history of preeclampsia, sociodemographic characteristics, and personal history factors). In the absence of high risk factors for preeclampsia, current evidence does not support the use of prophylactic low-dose aspirin for the prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.

Early-onset preeclampsia predisposes to preclinical diastolic left ventricular dysfunction in the fifth decade of life: An observational study.

BackgroundSystemic inflammation, endothelial dysfunction and deficient vascularization of either uterus or myocardium are mechanistic hallmarks of early-onset preeclampsia and heart failure with preserved ejection fraction (HFpEF). HFpEF is especially prevalent in elderly women and preceded in middle age by preclinical left ventricular (LV) diastolic dysfunction.To detect if preeclampsia predisposes to HFpEF at later age, echocardiographic indices of LV function and of LV structure and biomarkers of systemic inflammation and of endothelial dysfunction were compared in middle-aged women with a history of early-onset preeclampsia or uncomplicated pregnancy.Methods and findingsMiddle-aged women with a history of early-onset preeclampsia (n = 131) or uncomplicated pregnancy (n = 56) were prospectively recruited 9 to 16 years after pregnancy.Women with a history of preeclampsia had higher body mass index (p = 0.006), blood pressure (p<0.001) and plasma levels of interleukin-6 (p = 0.005) and soluble intercellular adhesion molecule-1 (sICAM-1) (p = 0.014). They had thicker septal (p = 0.001) and posterior (p = 0.003) LV walls and worse diastolic LV function evident from reduced mean mitral annular lengthening velocity (E’mean; p = 0.007) and higher ratio of early diastolic mitral flow velocity (E) over E’mean (E/E’mean; p<0.001). Differences of sICAM-1, E’mean and E/E’mean remained significant after accounting for BMI and blood pressure.ConclusionsHistory of preeclampsia predisposes in middle age to worse LV diastolic function, which could increase the likelihood of later HFpEF development. This predisposition derives not only from persistent cardiovascular risk but may also be caused by persistent endothelial dysfunction hindering adequate vascularization in the uterus during pregnancy and in the myocardium in middle age.

Similar pro-NT and pro-RLX2 levels after preeclampsia and after uncomplicated pregnancy

ObjectiveWomen are at increased risk of developing cardiovascular disease (CVD) after preeclampsia. Proneurotensin 1-117 (pro-NT) and prorelaxin 2 connecting peptide (pro-RLX2) have recently emerged as potential biomarkers for CVD risk in women. We assessed pro-NT and pro-RLX2 levels in women with and without a history of preeclampsia. Study design339 women with a history of early-onset preeclampsia and 327 women with an uncomplicated pregnancy underwent cardiovascular screening 10 years after delivery (the Preeclampsia Risk EValuation in FEMales (PREVFEM) cohort). Main outcome measuresPro-NT, a stable fragment of the neurotensin precursor, was assessed in the whole cohort. Pro-RLX2, the stable connecting peptide of the relaxin 2 prohormone, was assessed in a subset of this cohort, consisting of 27 women with a history of preeclampsia and 23 healthy controls. Associations between biomarker levels and traditional CVD risk factors in the preeclampsia and control group were assessed by Pearson’s correlation coefficient. ResultsWe found no differences in pro-NT and pro-RLX2 levels between the preeclampsia and control group. Pro-NT levels were associated with higher HbA1c levels (r = 0.113, p-value 0.045) and with BMI (r = 0.124, p-value 0.027), but only in the control group. Pro-RLX2 was related to current smoking and triglyceride levels in women with a history of preeclampsia and related to LDL-cholesterol in women with an uncomplicated pregnancy. ConclusionsPro-NT and pro-RLX2 levels were comparable in women 10 years after preeclampsia and women with an uncomplicated pregnancy. The role of pro-NT and pro-RLX2 in CVD development after preeclampsia should be further investigated.

Effect of early-onset preeclampsia on cardiovascular risk in the fifth decade of life

Women with hypertensive disorders in pregnancy, in particular early-onset preeclampsia, are at increased risk of developing cardiovascular disease later in life. These women have a more than 2-fold increased risk of dying from cardiovascular diseases. Most studies have focused on identification of risk factors shortly after pregnancy. Less is known on the prevalence of risk factors or actual signs of cardiovascular disease 5-20 years later. The presence of hypertension or metabolic syndrome can be seen as an opportunity for preventive interventions to reduce the development of severe cardiovascular diseases like myocardial infarction and stroke. To assess cardiovascular risk factors and established cardiovascular disease in women after early-onset preeclampsia, in the fifth decade of life. As a consequence, we can assess whether there is still a window of opportunity for preventive measures and to establish in what proportion of women cardiovascular disease already has developed. In a prospective observational study, cardiovascular risk assessment was performed in women with early-onset preeclampsia (<34 weeks' gestation) and normotensive controls (≥37 weeks' gestation) 9-16 years after their index pregnancy. Medical records of 2 tertiary hospitals in Amsterdam, The Netherlands, were screened consecutively, and all eligible women were invited. Cardiovascular risk assessment consisted of a questionnaire, blood pressure measurement, anthropometrics, and blood and urine for fasting lipids, lipoproteins, glucose levels, glycated hemoglobin, renal function, N-terminal brain natriuretic peptide, and albuminuria. History of cardiovascular diseases (ie, myocardial infarction and stroke) was determined. Prevalence of women presenting in an optimal window of opportunity for preventive measures was defined by the presence of cardiovascular risk factors (ie, hypertension and metabolic syndrome) but in the absence of established cardiovascular diseases (ie, myocardial infarction and stroke). Women with a history of early-onset preeclampsia (n= 131) had significantly greater systolic and diastolic blood pressure, greater body mass index, more often had an abnormal lipid profile (lower high-density lipoprotein levels, higher triglycerides), greater glycated hemoglobin, and greater levels of albuminuria compared to controls (n= 56). None of the women with a history of early-onset preeclampsia was diagnosed with cardiovascular disease; 38.2% were diagnosed with hypertension; and 18.2% were diagnosed with metabolic syndrome. A total of 42% met the criteria for the window of opportunity for preventive measures. In women with a history of an uncomplicated pregnancy, no women were diagnosed with cardiovascular disease; 14.3% were diagnosed with hypertension; 1.8% with metabolic syndrome. In this cohort, 14.3% met the criteria for the window of opportunity for preventive measures. A large proportion of women who experienced early-onset preeclampsia had major cardiovascular risk factors in the fifth decade of life, compared with healthy controls. These women are currently outside the scope of most preventive programs due to their relatively young age, but have important modifiable risk factors for cardiovascular diseases.

Long-term follow-up of psychosocial distress after early onset preeclampsia: the Preeclampsia Risk EValuation in FEMales cohort study

Objective: To examine long-term psychosocial distress in women with a history of early onset preeclampsia (PE) compared to a comparison group. Methods: Women with and without a history of early onset PE participating in the ‘Preeclampsia Risk EValuation in FEMales’ (PREVFEM) study were sent questionnaires, on average 14.1 years (SD = 3.2, range 5–23 years) after the index pregnancy. In total 265 (77%) women with PE and 268 (78%) age-matched women without PE returned questionnaires (mean age 43.5, SD =4.6 years). Group differences were examined on indicators of psychosocial distress, depressive symptoms, anxiety, fatigue, loneliness, marital quality, trait optimism and Type D personality, and unadjusted and adjusted for a priori chosen and study-specific covariates. In secondary analyses, the effect of previously detected hypertension was examined, as well as pregnancy-related events within the PE group. Results: Women with a history of PE reported more subsequent depressive symptoms (B = 0.70, 95% CI 0.09–1.32, p = 0.026) and more fatigue (B = 1.12, 95% CI 0.07–2.18, p = 0.037) compared to the non-PE group, but the differences explained less than 1% of the variance. The differences remained after adjustment for age, BMI and education level, and additional adjustment for partner, being unemployed and physical activity. No significant differences were observed for anxiety, loneliness, marital quality, optimism, or Type D personality. These differences were not explained by four-year previously measured elevated blood pressure in the PE group. Having had a stillborn child or early neonatal death during the index pregnancy was associated with higher depressive symptoms, anxiety, fatigue, and loneliness in the PE group, but these factors explained only a small proportion of the variance in these psychosocial distress factors. Conclusion: A history of early PE is associated with slightly higher levels of depressive symptoms and fatigue on average 14 years later, but this is unlikely to be of clinical relevance.

Maternal cardiac adaptation to subsequent pregnancy in formerly pre-eclamptic women according to recurrence of pre-eclampsia.

Left-ventricular remodeling in women with pre-eclampsia (PE) is concentric rather than eccentric, and tends to persist postpartum, particularly after early-onset PE. This study was designed to determine whether prepregnancy cardiac geometry and function along with cardiac adaptation to the subsequent pregnancy in former early-onset PE patients differs between those who do and those who do not develop recurrent PE later on in their second pregnancy. In 51 women with a history of early-onset PE, we performed serial cardiac ultrasound examinations and recorded automated measurements of blood pressure/heart rate before pregnancy and again at three consecutive times in the first half of their subsequent pregnancy. From the hospital records, we retrieved information on pregnancy outcome. We compared intergroup differences in cardiac indices using independent samples t-test, and intergroup differences in prepregnant cardiac ultrasound indices and subsequent pregnancy-induced cardiac adaptive response using repeated-measures ANOVA. PE recurred in 14/51 (27%) women. Preconception, the recurrent-PE group differed from the non-recurrent-PE group by having a lower left-ventricular mass (LVM) index (28 vs 32 g/m(2.7) , P < 0.05) and stroke volume (68 vs 77 mL, P < 0.05), and a higher resting heart rate (71 vs 64 bpm, P < 0.05). Despite these prepregnancy differences, the pregnancy-induced pattern of cardiac adaptive response was comparable in the two subgroups. After excluding hypertensive women, prepregnancy values for the LVM index remained significantly lower in the recurrent-PE group. Women with recurrent PE differed from the non-recurrent-PE group by having a lower LVM index and stroke volume, and a higher heart rate, but they responded to their subsequent pregnancy with a similar pattern of cardiac adaptation.

Cardiovascular Disease Risk Factors in Women With a History of Early-onset Preeclampsia

Cardiovascular Disease Risk Factors in Women With a History of Early-onset Preeclampsia