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

doi:10.1016/j.preghy.2016.04.001

Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health

Volume 6, Issue 2, April 2016, Pages 110-114

https://doi.org/10.1016/j.preghy.2016.04.001 Get rights and content

Highlights

•
Ten years after preeclampsia, traditional CVD risk assessment seems to be valuable.
•
Blood pressure needs to be assessed in 40-year old previously preeclamptic women.
•
Arterial stiffness and atherosclerosis markers did not uncover increased CVD risk.

Abstract

Objectives

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 10 years after index pregnancy.

Study design

A nested, matched, observational cohort study.

Main outcome measures

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.

Results

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.

Conclusions

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.

Introduction

Preeclampsia is a syndrome defined as new-onset hypertension and proteinuria after 20 weeks of gestation [1]. Preeclampsia represents not only a maternal risk during pregnancy, but epidemiological studies also show increased risk of premature cardiovascular disease (CVD) after delivery [2], [3]. Systematic reviews support the epidemiological findings and demonstrate an approximately doubled risk of ischemic heart disease, cerebrovascular incidents and mortality of CVD after preeclampsia [4], [5].

In 2011, American Heart Association changed their recommendations regarding women’s CVD risk. Preeclampsia was included as an independent factor heralding special attention. However, American Heart Association did not specify how and when the CVD risk of previously preeclamptic women should be assessed.

Still, the association between preeclampsia and premature CVD is incompletely understood. Studies have established that preeclampsia is a vascular disease related to traditional CVD risk factors such as hypertension, dyslipidemia and obesity. Prepregnancy CVD risk factors increase the risk of subsequent preeclampsia [6], [7]. Moreover, traditional CVD risk factors are more prevalent after preeclampsia [8], [9]. If preeclampsia itself additionally affects CVD risk is more uncertain. Indicating an additional intrinsic preeclamptic effect, studies found significantly more pronounced CVD risk in the combined presence of traditional risk factors and history of preeclampsia [3], [10].

Despite the established relation to traditional risk factors and a possible intrinsic effect, the value of a traditional CVD risk assessment including markers of arterial stiffness and atherosclerosis in women 10 years after preeclampsia remains unclear.

The primary objective of our study was to elucidate if an increased CVD risk can be detected as early as 10 years after preeclampsia. Therefore, the aim was to complete a comprehensive CVD risk assessment including markers of arterial stiffness, atherosclerosis and Framingham risk scores comparing women with previous preeclamptic pregnancies to women with previous normotensive pregnancies 10 years after delivery.

Section snippets

Methods

The source population for this observational study was a cohort comprised of approximately 1600 pregnant women studied at the tertiary referral hospital, Randers, Denmark in the period 2001–4 [11].

For the present study women were excluded if they were currently pregnant, breastfeeding, or living more than 100 km away from the hospital. Exposure was defined as having one preeclamptic pregnancy 2001–4. Preeclampsia diagnosis was defined as new-onset hypertension (systolic blood pressure ⩾ 140 mmHg

Results

We included 21 exposed women with previous preeclamptic pregnancies and 21 matched, unexposed women with previous normotensive pregnancies. The characteristics at follow-up and at index pregnancy are shown in Table 1. The mean age at follow-up was 40.7 years. Due to the age and time-since-delivery matched design, no differences in age and postpartum interval between the groups appeared.

At follow-up, two exposed women suffered from CVD, one from diabetes mellitus and significantly more from

Discussion

In a matched design, this study completed a comprehensive CVD risk assessment comparing women with previous preeclamptic pregnancies to women with previous normotensive pregnancies 10 years after delivery. In general, our study indicates that previously preeclamptic women had a more unfavorable CVD risk profile as early as 10 years after delivery. Two exposed women suffered from manifest CVD and one from diabetes mellitus.

We found that significantly more women with a history of preeclampsia

Acknowledgments

We would like to thank Anna Larsen, Department of Clinical Biochemistry, Randers Regional Hospital, Denmark for her immense contribution to this study.

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Cited by (31)

Maternal vascular indices at 36 weeks’ gestation in the prediction of preeclampsia
2024, American Journal of Obstetrics and Gynecology
Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce.
This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks’ gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks’ gestation.
This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks’ gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined.
The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%–92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%–76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%–88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%–71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%–64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%–52.0%) or high soluble fms-like tyrosine kinase-1–to–placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%–75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%–60.9%).
First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks’ gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.
Association of severe preeclampsia and vascular damage assessed by noninvasive markers of arterial stiffness
2023, Nefrologia
La preeclampsia (PE) es un trastorno hipertensivo del embarazo asociado a una elevada morbimortalidad materna y fetal, y un mayor riesgo futuro de complicaciones cardiovasculares.
Analizar si las mujeres que han tenido PE grave en su embarazo presentan parámetros de rigidez arterial (RA) superiores a las de aquellas cuya PE cursó sin signos de gravedad.
Se evaluaron 65 mujeres que habían desarrollado PE durante su gestación, divididas en 2 grupos: grupo de PE sin criterios de gravedad o PE no grave (n = 30) y grupo de PE con criterios de gravedad o PE grave (n = 35). Se determinó la velocidad de onda de pulso carótida-femoral (VOPcf), el índice de aumento central normalizado a 75 latidos por minuto (IAc75) y presión de aumento central (PAc) al mes y a los 6 meses posparto. La comparación de proporciones se llevó a cabo mediante la prueba de Chi-cuadrado, la comparación de medias entre grupos se utilizaron la prueba t de Student o la prueba de Mann-Whitney, y la comparación de medias de un mismo grupo en momentos evolutivos diferentes, la prueba t para o el test de Wilcoxon. La correlación, con y entre parámetros hemodinámicos, se llevó a cabo con el coeficiente de correlación de Spearman y la asociación entre variables demográficas, antecedentes personales y parámetros hemodinámicos, y valores alterados de RA se llevó a cabo mediante modelos de regresión lineal y logística.
Las mujeres con PE grave presentaban, al mes y a los 6 meses posparto, valores de presión arterial, tanto central como periférica, así como parámetros de RA y amplificación de pulso, superiores a aquellas mujeres cuya PE no revistió gravedad. Los valores del índice de aumento central (IAc) al mes y a los 6 meses posparto fueron superiores, aunque no de forma significativa, en el grupo de PE grave respecto al grupo de PE no grave (24,0 [16,5-34,3] vs. 19,0% [14-29] y 24,0 [14,0-30,0] vs. 20,0% [12,3-26,8], respectivamente). La velocidad onda de pulso carótida-femoral (VOPcf) fue superior de forma significativa, tanto al mes como a los 6 meses posparto en el grupo de PE grave respecto al grupo de PE no grave (10,2 [8,8-10,7] vs. 8,8 m/s [8,3-9,6] y 10,0 [8,8-10,6] vs. 8,8 m/s [8,3-9,3], respectivamente). La amplificación de la presión sistólica central y de la presión de pulso central fueron también superiores, aunque no de forma significativa, en el grupo de PE grave respecto al de PE no grave.
Las mujeres que han tenido PE grave presentan parámetros de RA más acusados que los de aquellas en las que la PE no revistió especial gravedad. Debiera evaluarse la conveniencia de incluir de forma rutinaria entre las mujeres que han tenido PE la determinación del IAc y especialmente la VOPcf, como estrategia de evaluación del riesgo cardiovascular.
Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with high maternal and fetal morbidity and mortality and increased future risk of cardiovascular complications.
To analyze whether women who have had PE with severe features in their pregnancy have higher arterial stiffness (AS) parameters than those whose PE course was without signs of severity.
Sixty-five women who developed PE during their gestation were evaluated, divided into two groups: PE group without severe features or non-severe PE (n = 30) and PE group with severe features or severe PE (n = 35). Carotid-femoral pulse wave velocity (cfPWV), central augmentation index corrected to a heart rate of 75 beats per minute (AIxc75) and central augmentation pressure (cAP) were determined one month and six months postpartum. Comparison of proportions was carried out using the chi-square test, comparison of means between groups using the Student's t-test or the Mann-Whitney test, and comparison of means of the same group at different evolutionary moments, using the t-test or the Wilcoxon test. Correlation, with and between hemodynamic parameters, was carried out with Spearman's correlation coefficient and the association between demographic variables, personal history and hemodynamic parameters, and altered arterial stiffness parameters was carried out using linear and logistic regression models.
Women with severe PE presented, both at 1 and 6 months postpartum, higher values of blood pressure, both central and peripheral, as well as AR and pulse amplification parameters, than those women whose PE was not severe. Central augmentation index (cAIx) values at 1 month and 6 months postpartum were higher, although not significantly, in the severe PE group compared to the non-severe PE group (24.0 (16.5-34.3) vs. 19.0% (14-29) and 24.0 (14.0-30.0) vs. 20.0% (12.3-26.8), respectively). Carotid-femoral pulse wave velocity (cfPWV) was significantly higher at both 1 and 6 months postpartum in the severe PE group compared to the non-severe PE group (10.2 (8.8-10.7) vs. 8.8 m/s (8.3-9.6) and 10.0 (8.8-10.6) vs. 8.8 m/s (8.3-9.3), respectively). Central systolic pressure and central pulse pressure amplification were also higher, although not significantly, in the severe PE group in comparison with the non-severe PE group.
Women who have had severe PE have more pronounced arterial stiffness parameters than those in whom PE was not particularly severe. The determination of cAIx and cfPWV, as a strategy for the assessment of cardiovascular risk, should be evaluated among women who have had PE.
Prospective Evaluation of Cardiovascular Risk 10 Years After a Hypertensive Disorder of Pregnancy
2022, Journal of the American College of Cardiology
Hypertensive disorders of pregnancy (HDP) are associated with increased risk of cardiovascular disease (CVD) 20-30 years later; however, cardiovascular (CV) risk in the decade after HDP is less studied.
The purpose of this study was to evaluate differences in CV risk factors as well as subclinical CVD among a well-characterized group of racially diverse patients with and without a history of HDP 10 years earlier.
This is a prospective study of patients with and without a diagnosis of HDP ≥10 years earlier (2005-2007) who underwent in-person visits with echocardiography, arterial tonometry, and flow-mediated dilation of the brachial artery.
A total of 135 patients completed assessments (84 with and 51 without a history of HDP); 85% self-identified as Black. Patients with a history of HDP had a 2.4-fold increased risk of new hypertension compared with those without HDP (56.0% vs. 23.5%; adjusted relative risk: 2.4; 95% CI: 1.39-4.14) with no differences in measures of left ventricular structure, global longitudinal strain, diastolic function, arterial stiffness, or endothelial function. Patients who developed hypertension, regardless of HDP history, had greater left ventricular remodeling, including greater relative wall thickness; worse diastolic function, including lower septal and lateral e’ and E/A ratio; more abnormal longitudinal strain; and higher effective arterial elastance than patients without hypertension.
We found a 2.4-fold increased risk of hypertension 10 years after HDP. Differences in noninvasive measures of CV risk were driven mostly by the hypertension diagnosis, regardless of HDP history, suggesting that the known long-term risk of CVD after HDP may primarily be a consequence of hypertension development.
Use of Race, Ethnicity, and National Origin in Studies Assessing Cardiovascular Risk in Women With a History of Hypertensive Disorders of Pregnancy
2021, CJC Open
Citation Excerpt :
A total of 524 records were obtained from our second search for recently published primary studies. After excluding records that did not meet our eligibility criteria, a total of 124 primary studies3,50-172 were included for full review (Supplemental Table S6). All included primary studies were published between 1976 and 2021, with most studies (72%) published in the last 10 years.
Women with a history of hyperBtensive disorders of pregnancy (HDP) are at particularly high risk for cardiovascular disease (CVD) and CVD-related death, and certain racial and ethnic subpopulations are disproportionately affected by these conditions. We examined the use of race, ethnicity, and national origin in observational studies assessing CVD morbidity and mortality in women with a history of HDP. A total of 124 studies, published between 1976 and 2021, were reviewed. We found that white women were heavily overrepresented, encompassing 53% of all participants with HDP. There was limited and heterogeneous reporting of race and ethnicity information across studies and only 27 studies reported including race and/or ethnicity variables in at least 1 statistical analysis. Only 2 studies mentioned the use of these variables as a strength; several others (k = 18) reported a lack of diversity among participants as a study limitation. Just over half of included articles (k = 68) reported at least 1 sociodemographic variable other than race and ethnicity (eg, marital status and income); however, none investigated how they might have worked synergistically or antagonistically with race and/or ethnicity to influence participants’ risk of CVD. These findings highlight significant areas for improvement in cardiovascular obstetrics research, including the need for more robust and standardized methods for collecting, reporting, and using sociodemographic information. Future studies of CVD risk in women with a history of HDP should explicitly examine racial and ethnic differences and use an intersectional approach.
Les femmes ayant des antécédents de troubles hypertensifs de la grossesse (THG) présentent un risque particulièrement élevé de maladies cardiovasculaires (MCV) et de décès liés à ces dernières, et certaines sous-populations raciales et ethniques sont touchées de manière disproportionnée par ces maladies. Nous avons examiné l’utilisation de la race, de l’ethnicité et de l’origine nationale dans les études observationnelles évaluant la morbidité et la mortalité liées aux MCV chez les femmes ayant des antécédents de THG. Un total de 124 études, publiées entre 1976 et 2021, ont été examinées. Nous avons constaté que les femmes blanches étaient fortement surreprésentées, puisqu’elles constituaient 53 % de l’ensemble des participantes atteintes de THG. Les renseignements relatifs à la race et à l’ethnicité étaient limités et hétérogènes d’une étude à l’autre, et seules 27 études ont indiqué avoir tenu compte de variables relatives à la race ou à l’ethnicité dans au moins une analyse statistique. Seules deux études ont mentionné l’utilisation de ces variables comme un point fort; plusieurs autres (k = 18) ont signalé un manque de diversité parmi les participantes comme une limite de l’étude. Un peu plus de la moitié des articles inclus (k = 68) ont fait état d’au moins une variable sociodémographique autre que la race et l’ethnicité (p. ex., l’état matrimonial et le revenu); aucun toutefois n’a étudié la manière dont ces variables auraient pu agir en synergie ou en opposition avec la race ou l’ethnicité pour influencer le risque de MCV des participantes. Ces résultats mettent en évidence des points importants à améliorer dans la recherche sur l’obstétrique cardiovasculaire, notamment la nécessité de méthodes plus fiables et normalisées en matière de collecte, de communication et d’utilisation des données sociodémographiques. Les prochaines études sur le risque de MCV chez les femmes ayant des antécédents de THG devraient examiner explicitement les différences raciales et ethniques et adopter une approche intersectionnelle.
Reduction of serum-induced endothelial STAT3(Y705) activation is associated with preeclampsia
2021, Pregnancy Hypertension
Citation Excerpt :
We hypothesized 1) that serum from preeclamptic women has different STAT3(Y705) phosphorylation capabilities in endothelial cells compared with serum from uncomplicated pregnant women; 2) that members of the VEGF superfamily contribute to the difference in STAT3(Y705) phosphorylation; and 3) that altered serum-induced endothelial STAT3(Y705) phosphorylation differences also exist in serum from previously preeclamptic women suffering from hypertension and carotid atherosclerotic plaques eight to eighteen years after deliveries. Serum samples used in the present study originated from three different clinical studies and all included women had singleton pregnancies in the period 1998–2008 [19–21]. In general, preeclampsia diagnosis was defined as new-onset hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) and proteinuria (≥300 mg/24 h or ≥ 30 mg/mmol albumin:creatinine random urine or ≥1+ on repeat dipstick).
Preeclampsia is associated with maternal morbidity and mortality during pregnancy, and also an increased cardiovascular disease (CVD) risk later in life. During preeclampsia, alterations in secreted placental factors leading to systemic maternal endothelial dysfunction are evident. However, little is known about the associated endothelial intracellular signaling. STAT3 is a latent cytoplasmic transcription factor involved in endothelial cell differentiation, survival, and angiogenesis. We aimed to test if preeclampsia and preeclampsia-related placental factors could alter serum-induced STAT3(Y705) activation in endothelial cells. Furthermore, if altered serum-induced endothelial STAT3 (Y705) activation is related to post-preeclamptic CVD risk.
HUVECs were used as a model of maternal endothelium. Experiments entailed addition of 20% human pregnancy serum as well as addition of recombinant PlGF, sFLT1 and VEGF-A_165a to the cells.
Levels of pSTAT3(Y705) related to STAT3 levels were evaluated by immunoblotting analysis.
Our results show that preeclamptic serum induces significantly lower STAT3(Y705) phosphorylation compared with uncomplicated pregnancy serum (P = 0.0089) in endothelial cells. Furthermore, STAT3(Y705) phosphorylation was not changed upon addition of PlGF, sFLT1, or VEGF-A_165a together with pregnancy sera compared with sera alone. Finally, sera from women with previous preeclampsia and current hypertension and carotid atherosclerotic plaques show significantly lower STAT3(Y705) phosphorylation capabilities compared with healthy women with previous uncomplicated pregnancies 8–18 years after deliveries (P = 0.029).
Reduction in serum-induced endothelial STAT3(Y705) activation may play an important role in the preeclampsia-associated endothelial dysfunction. Additionally, reduced endothelial STAT3(Y705) phosphorylation may contribute to increased post-preeclamptic CVD risk 8–18 years after delivery.
Cerebrovascular Pathophysiology in Preeclampsia and Eclampsia
2021, Chesley’s Hypertensive Disorders in Pregnancy
Hemorrhagic and ischemic strokes are, in addition to eclamptic fits, among the most important and feared causes of maternal morbidity and mortality in women with preeclampsia. Increasing evidence now indicates that both preeclampsia and eclampsia can impact long-term maternal cerebrovascular health. This chapter includes updated clinical, epidemiological, and mechanistic knowledge since the last edition, and adds important new sections on “Stroke in Pregnancy and Preeclampsia” and “Neurocognitive Functioning.” Future basic, translational, and clinical research are urgently needed to improve our mechanistic understanding of how preeclampsia and eclampsia damage the maternal brain, hopefully leading to improved prevention and treatment strategies. The important contributions of previous authors of this chapter, Gerda G. Zeeman and F. Gary Cunningham, are greatly appreciated.

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

Highlights

Abstract

Objectives

Study design

Main outcome measures

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgments

Lancet

Lancet

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Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother

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Prepregnancy cardiovascular risk factors as predictors of pre-eclampsia: population based cohort study

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Prepregnancy cardiometabolic and inflammatory risk factors and subsequent risk of hypertensive disorders of pregnancy

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Hypertension in pregnancy and later cardiovascular risk: common antecedents?

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Hypertensive disorders in pregnancy and subsequently measured cardiovascular risk factors

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High blood pressure during pregnancy is associated with future cardiovascular disease: an observational cohort study

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