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Introduction Accumulating evidence consistently demonstrates an increased risk and accelerated development of cardiovascular disease (CVD) risk in women with a history of a hypertensive disorder of pregnancy (HDP). Guidelines emphasize the emerging need for the prevention of CVD in these women, but fail to provide uniform recommendations on commencement and time interval in screening these patients. Objective The aim of this study is to investigate development of blood pressure, lipids and fasting glucose levels over time in women with a history of HDP in order to identify a window of opportunity for screening and prevention. Methods We identified women with self-reported normotensive pregnancy and HDP (NP, n = 1811; HDP, n = 1005) within the PREVEND study, a Dutch population-based cohort with a follow-up of maximum of 5 visits with 3-year intervals. Development of blood pressure, lipids, fasting glucose and Framingham 10-years CVD scores was longitudinally assed using generalized estimating equations. Results HDP”s present with overall higher and faster increasing prevalence of hypertension (p = 0.005), dyslipidemia (p = 0.009) and glucose disturbances (p = 0.002), reflecting in the use of medication (p Conclusion Women with a history of HDP show early development of hypertension, dyslipidemia and glucose homeostasis disturbances. Based on this cohort study, calculated 10-years CVD risk and NNS indicate commencing CVRM screening in these women at age 45 would be feasible. Download : Download high-res image (385KB) Download : Download full-size image

Background Baseline distributions of pregnancy disorders' biomarkers PlGF and PAPP-A levels are primarily based on Western European populations of Caucasian ethnicity. Differences in PAPP-A and PlGF concentrations by ethnicity have been observed, with increased levels in Afro-Caribbean, East Asian, and South Asian women. Baseline concentrations of sub-Saharan African women have not been evaluated. Objectives To investigate PlGF and PAPP-A in a sub-Saharan African population and assess the performance of existing reference values of PAPP-A and PlGF. Methods A nested cross-sectional study was conducted in two public hospitals in Accra, Ghana. Out of the original 1010 women enrolled in the cohort, 398 participants were eligible for inclusion with a normotensive singleton gestation and serum samples taken between 56 and 97days of pregnancy. PAPP-A and PlGF concentrations were measured with an automated immunoassay. Multiple of the median (MoM) values corrected for gestation and maternal weight for PAPP-A and PlGF were calculated using reference values of a Dutch perinatal screening laboratory based on over 10.000 samples, and PlGF manufacturer reference values, respectively. Results The PAPP-A median MoM was 2.34 (interquartile range (IQR) 1.24–3.97). Median PlGF MoM was 1.25 (IQR 0.95–1.80). Correlation between PAPP-A and PlGF MoM values was 0.21. Median MoM values for PAPP-A and PlGF tended to be slightly different for various Ghanaian ethnic subgroups. Conclusions PAPP-A and PlGF MoM values appear to be substantially higher in a sub-Saharan African population compared to the Caucasian or Afro-Caribbean MoM values previously reported. The difference suggests the need for a specific correction factor for this population to avoid underestimation of risk for fetal aneuploidies or placental disorders when using PAPP-A and PlGF MoM for screening purposes.

Question Preeclampsia is associated with long-term chronic hypertension and accelerated development of atherosclerosis, which may lead to premature arterial calcifications and arterial stiffness. However, the degree and distribution of these subclinical signs of atherosclerosis in women with a history of preeclampsia has not been previously addressed. In this study, we prospectively evaluate arterial calcifications by low-dose computed tomography (CT) and arterial stiffness by pulse wave velocity (PWV) in asymptomatic women with a history of preeclampsia. Methods Women with a history of preeclampsia ( N = 153) who participated in a prospective multicenter evaluation of cardiovascular health at age 45–55 years were screened for subclinical arterial disease using low-dose CT and pulse wave velocity (PWV) analysis. Coronary artery calcium score (CACS), thoracic aortic calcium score (TACS) excluding the aortic arch, and valvular calcium score (VCS) were assessed on a non-contrast cardiac CT scan and carotid siphon calcium score (CSCS) on a non-contrast carotid siphon scan. PWV was assessed as a measure of arterial stiffness (TensioMed Arteriograph). Correlations between vascular calcifications and the relationship between vascular calcifications and CVD risk factors were assessed. Results Study participants had a mean age at inclusion of 49.0 years (SD 3.9 years). Of these, 54.6% had hypertension and 35.3% fulfilled criteria for metabolic syndrome. Vascular calcifications were seen in 110 women (71.9%) on low-dose CT: 49 (32.0%) had CACS >0; 22 (14.9%) had TACS >0; 5 (3.3%) had VCS >0 and 95 (69.9%) had CSCS >0. CACS was strongly correlated with TACS ( R = 0.98, p 0 and hypertension (OR 2.50, 95%CI 1.22–5.13). The presence of calcifications (CACS >0) was not related to other cardiovascular risk factors including obesity, smoking, hyperlipidemia and increased PWV. Conclusions Coronary and vascular calcifications in general are common in women with a history of preeclampsia at age 45–55 years. Only CACS >0 appears to be associated with chronic hypertension, but not with increased arterial stiffness or other cardiovascular risk factors.

Introduction In the past decades evidence has accumulated that women with reproductive and pregnancy related disorders are at increased risk of developing cardiovascular disease (CVD) in the future. Up to now there is no standardized follow-up of these women since guidelines on cardiovascular risk management for this group are lacking. However, early identification of high-risk populations followed by prevention and treatment of CVD risk factors has the potential to reduce CVD incidence. Objective The Dutch Society of Obstetrics and Gynaecology initiated a multidisciplinary working group (gynecologists, cardiologist, vascular internist, radiologist, general practitioner, epidemiologist and representatives of patient associations) to develop a guideline for cardiovascular risk management after reproductive and pregnancy related disorders. Methods The guideline was developed using the “Appraisal of Guidelines for Research and Evaluation” instrument. The guideline addresses the cardiovascular risk consequences of gestational hypertension, preeclampsia, preterm delivery, small-for-gestational-age infant, recurrent miscarriage, polycystic ovary syndrome and premature ovarian insufficiency. The best available evidence on these topics was gathered by systematic review and the relation between the reproductive or pregnancy related disorders and CVD risk and risk factors was assessed by meta-analysis. Recommendations for clinical practice were formulated based on the number and quality of the studies and presence or absence of a relative risk > 2 of developing CVD events and/or risk factors from the meta-analysis. The Dutch societies of gynaecologists, cardiologists, vascular internists, radiologists, and general practitioners endorsed the guideline to ensure support for implementation in clinical practice. Results For all reproductive and pregnancy related disorders only a moderate increased relative risk ( 2) was found for overall CVD, except for preeclampsia (relative risk 2.15, 95% CI 1.76–2.61). Based on the current available evidence, follow-up is only recommended for women with a history of preeclampsia. A cardiovascular risk profile should be offered at the age of 50 years. Assessment of CVD risk and treatment of cardiovascular risk factors should be performed according to the Dutch guideline for cardiovascular risk management. For all reproductive and pregnancy related disorders optimization of modifiable cardiovascular risk factors is recommended to reduce the risk of future CVD. Conclusion In this guideline we present the recommendations for cardiovascular risk management after reproductive and pregnancy related disorders. To the best of our knowledge we are the first to make such recommendations in a national guideline.

Introduction Women with a history of preeclampsia (PE) have an increased risk to develop cardiovascular and renal disease later in life. Pre-existing cardiovascular risk factors may play an important role, on the other hand the transient presence of placenta ischemia might induce persistent changes in the maternal cardiovascular system. Objective We aimed to assess whether exposure to placental ischemia during pregnancy enhances long-term effects on the maternal cardiovascular and renal systems in rats using the Reduced Uterine Perfusion Pressure (RUPP) model for PE. Methods At gestational day (gd) 14, Sprague Dawley rats were randomized to two groups: SHAM (n = 12) or RUPP (n = 21). The RUPP procedure involved partial clipping of the lower abdominal aorta and both ovarian arteries to reduce placental flow. Post delivery, rats were followed for 8 weeks after which we measured mean arterial pressure (MAP, carotid), GFR (transcutaneous, sinistrin), albuminuria (24-h) and cardiac function (cardiac ultrasound). All rats were sacrificed for tissue collection and mesenteric arteries were used for reactivity experiments to assess peripheral arterial function. Parametric data are presented as mean ± SD and non-parametric data as median (25–75 percentile), and were respectively analyzed with student T-test or Mann–Whitney U-test. Morphologic and transcriptional analyses are ongoing. Results The mean weight gain of the RUPP rats during pregnancy (gd13–gd19) was significantly lower compared to the SHAM operated rats [30 ± 18 g vs 63 ± 12; p Conclusions We show that exposure to experimental placenta ischemia is accompanied by subtle disturbances in maternal cardiac and renal function after recovery from PE. Our results indicate that placental ischemia itself can result in persistent changes in the cardiac and renal systems, although at this early stage no differences in vascular reactivity or blood pressure regulation were observed. Future studies should elucidate whether aging, a second hit or underlying disease aggravate target organ dysfunction after placental ischemia. Results Despite being all followed up for 27.5 yrs, the exposed women were older when they had their first pregnancy with and median age of 24.9 yrs ((5th;95th percentiles) (19.5;27.3)) vs. 24.6 yrs (19.4;27.3), p Conclusion A small extra vitamin D in fetal life from food fortification reduced risk of PE later in life. The effect was mainly seen among current smokers.

Introduction Depression is among the leading causes of disability adjusted life years. For women in their fertile ages the occurrence of depression is of great impact for their selves and families. We analyzed the association between term hypertensive pregnancy disorders and depression scores. Methods Two to six years after pregnancy, women with a history of term preeclampsia or gestational hypertension were included in the hypertensive pregnancy cohort (HTP cohort) (n = 257). Controls were women who had an uncomplicated pregnancy (n = 83) (NTP cohort).The Edinburgh Postnatal Depression Scale (EPDS score) (Cox et al., 1987) was used to determine individual depression scores. Depression was defined as an EPDS score >12 or the use of antidepressants. Potential differences between groups were compared using the Student’s T test, the Chi-squared test ( X 2 test), or the Mann–Whitney U test when appropriate. We used logistic regression analyses to adjust for potential confounders. Results Women in the HTP cohort had higher depression scores than women in the NTP cohort (Table 1) and were more often depressed (OR 5.8 (1.4–24.6)). After correction for parity (adjusted OR 1.3 (0.8–2.0), BMI (adjusted OR 1.2 (1.1–1.2) and antihypertensive medication use (adjusted OR 1.1 (0.3–3.8), no significant differences were found in depression rates with an adjusted OR 4.2 (0.9–18.8). Conclusion More than three years postpartum women with a history of term hypertensive pregnancy disorders are more often depressed compared to women with a history of a normotensive pregnancy. Download : Download full-size image

Introduction In a previous study, we described the predictive value of first-trimester pregnancy-associated plasma protein-A (PAPP-A), free beta-subunit of human chorionic gonadotrophin (fb-hCG), Placental Growth Factor (PlGF) and A Desintegrin And Metalloproteinase 12 (ADAM12) for early onset preeclampsia (delivery Objectives The objective of the current study was to obtain the predictive value of these serum makers, for both early onset PE (EOPE) and late onset PE (LOPE), combined with maternal characteristics and first-trimester maternal mean arterial blood pressure (MAP). Methods This was a nested case-control study, using stored first-trimester maternal serum from 167 women who subsequently developed PE, and 500 uncomplicated singleton pregnancies which resulted in a live birth=>37 weeks. Maternal characteristics (i.e. medical records, parity, weight, length) MAP and pregnancy outcome (i.e. gestational age at delivery, birthweight, fetal sex) were collected for each individual and used to calculate prior risks for PE in a multiple logistic regression model. MAP values and marker levels of PAPP-A, fb-hCG, PlGF and ADAM12 were expressed as multiples of the gestation-specific normal median (MoMs). Subsequently, MoMs were log-transformed and compared between PE and controls using Student's t-tests. Posterior risks were calculated using different combinations of variables;(1) maternal characteristics, serum markers, and MAP separately (2) maternal characteristics combined with serum markers or MAP (3) maternal characteristics combined with serum markers and MAP. The model-predicted detection rates (DR) for fixed 10% false-positive rates were obtained for EOPE and LOPE with or without intra-uterine growth restriction (IUGR,birth weight Results The maternal characteristics: maternal age, weight, length, smoking status and nulliparity were discriminative between PE and control groups and therefore incorporated in the multiple logistic regression model. MoM MAP was significantly elevated (1.10 p p p =0.016; 0.90 p =0.029) in the EOPE and LOPE group, respectively. The differences in markers for IUGR groups were larger. The estimated DRs of the three different models are presented in the table. Screening testDetection rate (95% confidence interval) for fixed 10% FPREarly onset PELate onset PE+ IUGRn=13−IUGRn=55Alln=99+IUGRn=49−IUGRn=50Maternal characteristics47 (34–61)50 (23–77)46 (32–62)25 (17–35)31 (18–47)20 (12–38)PlGF25 (16–38)33 (14–61)23 (14–37)28 (20–39)38 (26–53)16 (8–29)MAP45 (33–58)39 (23–71)47 (33–61)32 (23–43)22 (11–38)40 (27–54)Maternal characteristics+PlGF52 (38–67)56 (26–81)52 (35–68)40 (30–51)57 (41–72)26 (15–40)MAP58 (43–71)60 (31–83)57 (41–72)46 (36–57)37 (22–55)52 (38–66)MAP and PlGF64 (48–77)67 (35–88)63 (45–78)58 (49–70)66 (47–80)52 (38–67) Conclusion This study demonstrates that first-trimester MAP and PlGF combined with maternal characteristics are promising markers in risk assessment for PE. Combination of markers proved especially useful for risk assessment for term PE. Detection rates were higher in the presence of IUGR.

Introduction Hypertensive disorders in pregnancy, including Pregnancy Induced Hypertension (PIH), are important causes of morbidity and mortality in pregnancy. Identifying women at high risk will allow for early management to reduce complications of PIH. Objectives The objectives were to determine the incidence of PIH among pregnant women and develop risk prediction models for early detection of women at increased risk of PIH. Methods: A longitudinal cohort study involving 2539 pregnant women attending antenatal clinic in the Greater Accra region of Ghana was conducted between February and May 2010. The outcome, PIH, was defined as systolic or diastolic blood pressure BP of 140 mmHg or 90 mmHg respectively. Logistic regression was used to derive the prediction models and bootstrapping technique was used to internally validate them. A score chart was used to classify pregnant women into low, moderate and high risk of developing PIH. Results The incidence of PIH was 8.0% (95% C.I: 7.98–8.02%) and 10.9% (95% C.I:10.89–10.91%) in nulliparous and multiparous women respectively. Systolic blood pressure, diastolic blood pressure, history of hypertension in parents, family history of diabetes, proteinuria, body mass index (BMI) were among independent predictors in early pregnancy of subsequent PIH. The prognostic performance, estimated by the area under the Receiver Operating Characteristic (ROC) curve, ranged between 0.64 and 0.84 for the models for nulliparous and multiparous. Conclusion Using a limited set of maternal characteristics, pregnant women at increased risk of developing PIH can be identified. Categorizing women by risk of PIH and providing tailored antenatal care will minimize complications of PIH.

Introduction Several studies have shown that the risk of premature cardiovascular disease (CVD) is increased after maternal placental syndromes (MPS), including hypertensive disorders and placental abruption. Although a high prevalence of CVD risk factors has been observed for women with a history of preeclampsia and pregnancy-induced hypertension, it is unclear whether patients with previous placental abruption exhibit the same cardiovascular risk profile. Objectives To investigate the association of placental abruption with the presence of modifiable CVD risk factors that may be of potential use for prevention programs. Methods We performed a case–control study of 75 women with a history of placental abruption and a control group of 79 women with uneventful pregnancies. At 6–9 months postpartum we measured the following CVD risk factors: blood pressure, body-mass index (BMI), fasting blood glucose levels, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and CRP. Baseline variables in the two groups with and without a previous abruption were expressed as means and standard deviations (SD). Where appropriate, means were adjusted for potential confounders using a generalized linear model. Data were further stratified for women with or without additional MPS-related complications, i.e. preeclampsia, gestational hypertension and intrauterine growth restriction. Results Women who experienced placental abruption had a significantly higher systolic and diastolic blood pressures, BMI, fasting blood glucose levels, CRP, total cholesterol, HDL-cholesterol, LDL-cholesterol and cholesterol/HDL ratio, as compared to controls. Characteristics Reference group n = 79 Placental abruption n = 75 P-value Systolic BP 114 (13) 122 (13) Diastolic BP 75 (7) 79 (11) 0.022 CRP 0.65 (1.03) 1.89 (3.04) 0.008 Total cholesterol 143.7 (55.4) 194.3 (36.3) HDL 45.6 (16.8) 54.2 (13.9) 0.001 LDL 83.4 (42.9) 117.6 (35.4) Triglycerides 83.5 (41.0) 94 (46.1) 0.134 Cholesterol/HDL ratio 3 (1.54) 3.54 (1.16) 0.02 Fasting glucose 3.89 (1.30) 5.09 (0.35) These associations remained significant in women with previous placental abruption without concomitant other MPS only for plasma lipid profile, BMI and fasting blood glucose levels, but not for diastolic and systolic blood pressure. Conclusion A history of placental abruption is independently associated with increased BMI, fasting blood glucose levels, total cholesterol and LDL-cholesterol postpartum. Early detection of CVD risk factors in women with previous placental abruption offers an attractive opportunity for primary and secondary prevention.

Introduction Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women. Epidemiological studies have shown an increased risk of a CVD event in women who have had a hypertensive disorder in one of their previous pregnancies. These data also suggest that these increased risks are associated with severity and time of onset of pre-eclampsia. Risk factors for CVD have not yet been compared between women who experienced early versus late and mild versus severe hypertensive disorders of pregnancy. Objectives In this study we compared classic CVD risk factors of postpartum women with previous early-onset preeclampsia (EOPE), late onset pre-eclampsia (LOPE) and pregnancy induced hypertension (PIH). Methods A total of 81 women with previous EOPE (delivery required ⩽34weeks), 76 with LOPE (delivery ⩾36weeks) and 229 with PIH were included along with 79 healthy controls. Statistical analyses were performed using generalized linear models in PASW statistics 17.0, SPSS Inc. Results Adjusted means of blood pressure, fasting plasma glucose levels and LDL levels were significantly increased after all hypertensive disorders of pregnancy compared to controls. This increase of CVD risk factors was significantly correlated with severity and time of onset of the disease (Table 1). The prevalence of metabolic syndrome (BMI>30kg/m 2 and ⩾2 of the following; triglycerides ⩾150mg/dl, HDL cholesterol ⩾50mg/dl, systolic blood pressure ⩾130 or diastolic blood pressure ⩾85 and fasting plasma glucose levels ⩾100mg/dl) did not differ between the study groups; women who had PIH had the highest number of components of the metabolic syndrome (). Conclusion These results further establish the predisposition to CVD in women with previous pre-eclampsia or PIH. EOPE is associated with a more pronounced CVD risk factor profile than LOPE or PIH, which may explain the previously described higher CVD event risk.

Introduction: Large population studies have observed an increased risk for cardiovascular disease in later life for former preeclamptic women: 1.8 fold for (non)fatal stroke and 2.2 fold for (non)fatal ischemic heart disease. Since the absolute 10-year cardiovascular risk is low, primary postpartum lifestyle intervention is suggested. However, how effective lifestyle intervention after preeclampsia may be in lowering the cardiovascular risk, is not yet known. This study aimed to estimate the potential benefit of primary lifestyle intervention after preeclampsia to lower cardiovascular risk. Material and methods: Pubmed and Cochrane were first searched for studies that compared postpartum cardiovascular parameters, like blood pressure and BMI, of former preeclamptic women to non-preeclamptic women. Second, Pubmed and Cochrane were searched for studies, that reported the effect of lifestyle intervention on cardiovascular parameters. Studies that reported on women between 25 and 45 years of age were selected for further use. For each cardiovascular parameter a consensus based realistic effect and 90%-confidence interval were calculated. With these results the cardiovascular parameters for a virtual population of former preeclamptic women after lifestyle intervention were estimated and compared to non-preeclamptic women. For each parameter the median and 90%-confidence interval of the difference was calculated. These results were put into existing risk prediction models to estimate the remaining odds-ratio for cardiovascular disease in former preeclamptic women after lifestyle intervention. Results: The first search resulted in 10 studies ranging from 6 months to 19 years postpartum. The second search resulted in 17 studies. In former preeclamptic women the remaining odds-ratio of cardiovascular disease after lifestyle intervention for (non)fatal stroke was estimated at 1.52 (90%-CI 1.11-2.44) and for (non)fatal ischemic heart disease at 1.81 (90%-CI 1.53-2.10). Discussion: Although in former preeclamptic women lifestyle intervention decreases cardiovascular risk, they still remain at an increased risk for remote cardiovascular disease.