Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands: a national cohort study.

BACKGROUND: Hypertensive disorders of pregnancy are associated with cardiovascular disease later in life. Given that hypertensive disorders of pregnancy often occur at a relatively young age, there might be an opportunity to use preventive measures to reduce the risk of early cardiovascular disease and mortality. The aim of this study was to assess the risk of cardiovascular mortality in women after a hypertensive disorder of pregnancy. METHODS: In this population-based cohort study, the Netherlands Perinatal Registry (PRN) and the national death registry at the Dutch Central Bureau for Statistics were linked. We analysed women in the Netherlands with a first birth during 1995-2015 to determine the association between cardiovascular mortality and hypertensive disorders of pregnancy (based on recorded diastolic blood pressure or proteinuria, or both). We analysed the association between the highest diastolic blood pressure measured in pregnancy and cardiovascular mortality and constructed survival curves to assess cardiovascular mortality after hypertensive disorders of pregnancy, specifically pre-eclampsia and gestational hypertension. To differentiate between the severity of hypertensive disorders of pregnancy, cardiovascular mortality was assessed in women with a combination of hypertensive disorders of pregnancy with preterm birth (gestational age <37 weeks) and growth restriction (birthweight in the 10th percentile or less). All hazard ratios (HRs)were adjusted for maternal age. FINDINGS: Between Jan 1, 1995, and Dec 31, 2015, the PRN contained 2 462 931 deliveries and 1 625 246 women. In 1 243 890 women data on their first pregnancy were available and were included in this analysis after linkage, with a median follow-up time of 11·2 years (IQR 6·1-16·3). 259 177 (20·8%) women had hypertensive disorders of pregnancy, and of these 45 482 (3·7%) women had pre-eclampsia and 213 695 (17·2%) women had gestational hypertension; 984 713 (79·2%) women did not develop hypertension in their first pregnancy. Compared with women without hypertensive disorders of pregnancy, the risk of death from any cause was higher in women who had hypertensive disorders (HR 1·30 [95% CI 1·23-1·37], p<0·001), pre-eclampsia (1·65 [1·48-1·83]; p<0·0001), and gestational hypertension (1·23 [1·16-1·30]; p<0·0001). Those women with pre-eclampsia had a higher risk of cardiovascular mortality compared with those without any hypertensive disorders of pregnancy (adjusted HR 3·39 [95% CI 2·67-4·29]), as did those with gestational hypertension (2·22 [1·91-2·57]). For women with a history of hypertensive disorders of pregnancy combined with preterm birth (gestational age <37 weeks) and birthweight in the 10th percentile or less, the adjusted HR for cardiovascular mortality was 6·43 (95% CI 4·36-9·47), compared with women without a hypertensive disorder of pregnancy. The highest diastolic blood pressure measured during pregnancy was the strongest risk factor for cardiovascular mortality (for 80-89 mm Hg: adjusted HR 1·47 [95% CI 1·00-2·17]; for 130 mm Hg and higher: 14·70 [7·31-29·52]). INTERPRETATION: Women with a history of hypertensive disorders of pregnancy have a risk of cardiovascular mortality that is 2-3 times higher than that of women with normal blood pressure during pregnancy. The highest measured diastolic blood pressure during pregnancy is an important predictor for cardiovascular mortality later in life; therefore, women who have hypertensive disorders of pregnancy should be given personalised cardiovascular follow-up plans to reduce their risk of cardiovascular mortality. FUNDING: None.

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. METHODS AND FINDINGS: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. CONCLUSIONS: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. TRIAL REGISTRATION: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.

SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NTR6134; Pre-results.

Increased cardiovascular disease risk in women with a history of recurrent miscarriage.

INTRODUCTION: Cardiovascular disease is the leading cause of death in women. Observational studies suggest that women with a history of recurrent miscarriage have an increased risk of cardiovascular disease. MATERIAL AND METHODS: Women who visited the recurrent miscarriage clinic at Leiden University Medical Center between 2000 and 2010 and who had their third consecutive miscarriage before the age of 31 years, were invited to participate in this follow-up study (between 2012 and 2014). The reference group consisted of women with at least one uncomplicated pregnancy and no miscarriage, matched by zip code, age, and date of pregnancy. All women were invited for risk factor screening, including physical examination and blood collection. Main outcome measures were the (extrapolated) 10- and 30-year cardiovascular risk scores using the Framingham risk score. A subanalysis was performed for women with idiopathic recurrent miscarriage. RESULTS: Thirty-six women were included in both groups. Mean follow up was 7.5 years. Women with recurrent miscarriage had a significantly higher extrapolated 10-year cardiovascular risk score (mean 6.24%, SD 5.44) compared with women with no miscarriage (mean 3.56%, SD 1.82, P = .007) and a significantly higher 30-year cardiovascular risk score (mean 9.86%, SD 9.10) compared with women with no miscarriage (mean 6.39%, SD 4.20, P = .04). Similar results were found in women with idiopathic recurrent miscarriage (n = 28). CONCLUSIONS: Women with a history of recurrent miscarriage differ in cardiovascular risk profile at a young age compared with women with no miscarriage. The findings support an opportunity to identify women at risk of cardiovascular disease later in life and a possible moment for intervention.

Reduction of cardiovascular risk after preeclampsia: the role of framing and perceived probability in modifying behavior.

OBJECTIVE: To reduce cardiovascular risk after preeclampsia, we investigated the effect of framing, the perceived probability and its interaction, on the willingness to modify behavior. METHODS: Participants scored their willingness to modify behavior on two cases with different probabilities of developing cardiovascular disease. Both cases were either presented as "chance of health" or "risk of disease". RESULTS: 165 questionnaires were analyzed. ANOVA revealed a significant effect of probability, non-significant effect of framing and a non-significant interaction between probability and framing. CONCLUSION: Perceived probability influences willingness to modify behavior to reduce cardiovascular risk after preeclampsia; framing and the interaction was not of influence.

Counselling and management of cardiovascular risk factors after preeclampsia.

OBJECTIVE: Women with a history of preeclampsia have an increased risk of cardiovascular disease. Gynaecologists have an important role in the counselling and management of cardiovascular risk factors after preeclampsia. We aimed to assess the role of gynaecologists in informing women on interventions and risk factor follow-up after early and late preeclampsia. METHODS: In 2011 and 2014, all gynaecologists in the Netherlands were invited for a questionnaire. Results were analysed and compared over time. RESULTS: In 2011, the questionnaire was answered by 244 and in 2014 by 167 gynaecologists. After early preeclampsia, in 2011, 53% advised yearly blood pressure measurements; this increased to 65% in 2014. Over the years there was an increase in respondents advising an increased physical activity of 35% in 2011 to 56% in 2014. After late preeclampsia, in 2011, 36% advised yearly blood pressure measurements; this increased to 46% in 2014. There was an increase in gynaecologists advising increased activity (32% in 2011 to 56% in 2014). In both early and late preeclampsia, smoking cessation and weigh loss were advised often (70-80%); glucose and lipid screening were advised rarely (6-20%). CONCLUSION: Although there is still a considerable scope for improvement, an increasing number of gynaecologists advise women after preeclampsia on preventive interventions to decrease risks of cardiovascular disease.

Homocysteinemia After Hypertensive Pregnancy Disorders at Term.

BACKGROUND: Results from a number of long-term follow-up studies have suggested that hypertensive disorders in pregnancy are associated with increased risk of cardiovascular disease later in life. More recently, this putative relationship has been substantiated with findings of elevated cardiovascular risk factors, such as lipid profiles and glucose, in women with a history of hypertensive pregnancy disorders. Homocysteine is a sensitive indicator of increased risk but data on homocysteine levels in women with a history of hypertensive pregnancy disorders are inconsistent. DESIGN: This cohort study included 279 women with a history of hypertensive pregnancy disorders at term and 85 women with a history of uncomplicated pregnancies who participated in the Hypitat Risk Assessment Study (HyRAS). METHODS: Blood samples for total homocysteine determination were taken 2.5 years postpartum. Homocysteine levels were determined in plasma using an immunoassay. RESULTS: Women with a history of hypertensive pregnancy disorders had significant higher median homocysteine levels (10.66 µmol/L) 2.5 years postpartum compared with women with a history uncomplicated pregnancies (9.82 µmol/L; p=0.002). Women with a history of hypertensive pregnancy disorders had a higher risk of having a homocysteine level in the highest quartile (odds ratio 3.4, 95% confidence interval 1.5-7.6). CONCLUSION: At 2.5 years postpartum, women with a history hypertensive pregnancy disorders had higher homocysteine levels than women who had uncomplicated pregnancies. Although higher homocysteine levels might be a potential link between a history of hypertensive pregnancy disorders and increased cardiovascular disease risk later in life, the clinical implications remain an area for future research.

Prevention of cardiovascular risk in women who had hypertension during pregnancy after 36 weeks gestation.

OBJECTIVE: To analyse preventive interventions of women with cardiovascular risk factors postpartum. METHODS: 3.5 years postpartum, women with history of hypertension in pregnancy were invited for a questionnaire, 1 year after a cardiovascular risk assessment. RESULTS: Two hundred and fifty-seven women completed the questionnaire. At risk factor analyses, 35% had hypertension, 37% abnormal lipid- or glucose levels, 63% BMI ≥ 25 and 19% smoked. One year later, 36% of women with hypertension used anti-hypertensives, 0% of women with abnormal laboratory findings used anti-cholesterol and 1% anti-diabetes medication, 31% of the obese women achieved BMI reduction (≥ 5%), 42% of the women who smoked, quit. CONCLUSION: A minority improved their risk profile.

Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension.

Observational studies have shown an increased lifetime risk of cardiovascular disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This risk is related to the severity of the pregnancy-related hypertensive disease and gestational age at onset. However, it has not been investigated whether these differences in CVD risk factors are already present at postpartum cardiovascular screening. We evaluated postpartum differences in CVD risk factors in 3 subgroups of patients with a history of hypertensive pregnancy. We compared the prevalence of common CVD risk factors postpartum among 448 women with previous early-onset preeclampsia, 76 women with previous late-onset preeclampsia, and 224 women with previous pregnancy-induced hypertension. Women with previous early-onset preeclampsia were compared with women with late-onset preeclampsia and pregnancy-induced hypertension and had significantly higher fasting blood glucose (5.29 versus 4.80 and 4.83 mmol/L), insulin (9.12 versus 6.31 and 6.7 uIU/L), triglycerides (1.32 versus 1.02 and 0.97 mmol/L), and total cholesterol (5.14 versus 4.73 and 4.73 mmol/L). Almost half of the early-onset preeclampsia women had developed hypertension, as opposed to 39% and 25% of women in the pregnancy-induced hypertension and late-onset preeclampsia groups, respectively. Our data show differences in the prevalence of common modifiable CVD risk factors postpartum and suggest that prevention strategies should be stratified according to severity and gestational age of onset for the hypertensive disorders of pregnancy.

Systematic review and metaanalysis on nonclassic cardiovascular biomarkers after hypertensive pregnancy disorders.

OBJECTIVE: The aim of this study was to investigate which nonclassic cardiovascular biomarkers are associated with persistent endothelial dysfunction after pregnancy in women with a history of hypertensive pregnancy disorders compared with women with uncomplicated pregnancies. STUDY DESIGN: This was a systematic review and metaanalysis of observational studies. A search was performed in PubMed, Embase, Cochrane, and Cinahl including articles from inception to Feb. 27, 2013. Included were cohort studies and case-control studies. Cases were women with a history of hypertension in pregnancy, control subjects were women with a history of uncomplicated pregnancies. Of the 3136 found, 21 studies on 16 nonclassic cardiovascular biomarkers are described in this review; 12 studies on 5 biomarkers were included in the metaanalysis. RESULTS: Women with a history of hypertensive pregnancy disorders had a higher homocysteine level compared with women with a history of uncomplicated pregnancies (5 studies; pooled mean difference, 0.77 ng/mL; 95% confidence interval, 0.27-1.26; P < .01). For the other nonclassic cardiovascular biomarkers including markers in areas of inflammation, thrombosis, and angiogenesis, we found no significant differences. CONCLUSION: This review and metaanalysis showed that women with a history of hypertensive pregnancy disorders have higher homocysteine levels compared with women with a history of uncomplicated pregnancies. These data suggest persistent endothelial alteration after pregnancies complicated by hypertensive disorders.

Cost-effectiveness analysis of cardiovascular risk factor screening in women who experienced hypertensive pregnancy disorders at term.

OBJECTIVES: To assess the cost-effectiveness of post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term. STUDY DESIGN: Two separate Markov models evaluated the cost-effectiveness analysis of hypertension (HT) screening and screening on metabolic syndrome (MetS), respectively, as compared to current practice in women with a history of term hypertensive pregnancy disorders. Analyses were performed from the Dutch health care perspective, using a lifetime horizon. One-way sensitivity analyses and Monte Carlo simulation evaluated the robustness of the results. RESULTS: Both screening on HT and MetS in women with a history of gestational hypertension or pre-eclampsia resulted in increase in life expectancy (HT screening 0.23year (95% CI -0.06 to 0.54); MetS screening 0.14years (95% CI -0.16 to 0.45)). The gain in QALYs was limited, with HT screening and MetS screening generating 0.04 QALYs (95% CI -0.12 to 0.20) and 0.03 QALYs (95% CI -0.14 to 0.19), resulting in costs to gain one QALY of €4228 and €28,148, respectively. Analyses for uncertainty showed a chance of 74% and 75%, respectively, that post-partum screening is cost-effective at a threshold of €60,000/QALY. CONCLUSIONS: According to the available knowledge post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term is likely to be cost-effective.

Induction of labour or expectant monitoring in hypertensive pregnancy disorders at term: do women's postpartum cardiovascular risk factors differ between the two strategies?

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in women in the western world. Several studies have described the association between hypertensive pregnancy disorders and CVD in later life. Our aim was to compare postpartum cardiovascular risk factors in women who had a shorter and women who had a longer exposure to endothelial activation during their term hypertensive pregnancy. STUDY DESIGN: We studied a subsample of women with pregnancy-induced hypertension or mild preeclampsia at term, who had participated in the randomized HYPITAT trial comparing induction of labour (IOL cohort) (n=110) or expectant monitoring (EM cohort) (n = 91). We assessed, 2.5 years postpartum, cardiovascular risk factors, i.e. blood pressure, anthropometrics, glucose, HbA1C, insulin, HOMA score, total cholesterol, HDL cholesterol, triglycerides, high sensitive CRP, micro-albumin and metabolic syndrome, and compared these risk factors between the induction and expectant groups. RESULTS: The mean time from randomization to delivery was 3.3 days in the induction group and 10.3 days in the expectant group (p<.001), generating a difference in exposure of 7 days. After a mean follow-up period of 2.5 years, the prevalence of hypertension (IOL 34%; EM 37%, p = .66) and metabolic syndrome (IOL 26%; EM 27%, p = 1.0) was similar in both groups. Furthermore, systolic and diastolic blood pressure, BMI, waist circumference, glucose, HbA1C, insulin, HOMA score, lipids, HsCRP-levels and micro-albumin were all comparable between women who had induction of labour and those who had expectant monitoring. CONCLUSION: In women with hypertensive disorders in pregnancy at term, induction of labour does not affect the clinical and biochemical cardiovascular profile at 2.5 years postpartum.

Cardiovascular risk estimation in women with a history of hypertensive pregnancy disorders at term: a longitudinal follow-up study.

BACKGROUND: Cardiovascular disease is associated with major morbidity and mortality in women in the Western world. Prediction of an individual cardiovascular disease risk in young women is difficult. It is known that women with hypertensive pregnancy complications have an increased risk for developing cardiovascular disease in later life and pregnancy might be used as a cardiovascular stress test to identify women who are at high risk for cardiovascular disease. In this study we assess the possibility of long term cardiovascular risk prediction in women with a history of hypertensive pregnancy disorders at term. METHODS: In a longitudinal follow-up study, between June 2008 and November 2010, 300 women with a history of hypertensive pregnancy disorders at term (HTP cohort) and 94 women with a history of normotensive pregnancies at term (NTP cohort) were included. From the cardiovascular risk status that was known two years after index pregnancy we calculated individual (extrapolated) 10-and 30-year cardiovascular event risks using four different risk prediction models including the Framingham risk score, the SCORE score and the Reynolds risk score. Continuous data were analyzed using the Student's T test and Mann-Whitney U test and categorical data by the Chi-squared test. A poisson regression analysis was performed to calculate the incidence risk ratios and corresponding 95% confidence intervals for the different cardiovascular risk estimation categories. RESULTS: After a mean follow-up of 2.5 years, HTP women had significantly higher mean (SD) extrapolated 10-year cardiovascular event risks (HTP 7.2% (3.7); NTP 4.4% (1.9) (p<.001, IRR 5.8, 95% CI 1.9 to 19)) and 30-year cardiovascular event risks (HTP 11% (7.6); NTP 7.3% (3.5) (p<.001, IRR 2.7, 95% CI 1.6 to 4.5)) as compared to NTP women calculated by the Framingham risk scores. The SCORE score and the Reynolds risk score showed similar significant results. CONCLUSIONS: Women with a history of gestational hypertension or preeclampsia at term have higher predicted (extrapolated) 10-year and 30-year cardiovascular event risks as compared to women with a history of uncomplicated pregnancies. Further large prospective studies have to evaluate whether hypertensive pregnancy disorders have to be included as an independent variable in cardiovascular risk prediction models for women.

Cardiovascular risk factors in women who had hypertensive disorders late in pregnancy: a cohort study.

OBJECTIVE: The purpose of this study was to determine cardiovascular risk factors in women with a history of hypertensive pregnancy disorders at term (HTP) 2.5 years after pregnancy. STUDY DESIGN: In a multicenter cohort study in The Netherlands from June 2008 through November 2010, cardiovascular risk factors were compared between women with a history of HTP (HTP cohort, n = 306) and women with a history of normotensive pregnancies at term (NTP cohort, n = 99). HTP women had participated in a randomized, longitudinal trial assessing the effectiveness of induction of labor in women with hypertensive pregnancy disorders at term. All women were assessed 2.5 years after pregnancy for blood pressure, anthropometrics, glucose, glycosylated hemoglobin, insulin, homeostatic model assessment score, total cholesterol, high-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and microalbumin and metabolic syndrome. RESULTS: After a mean follow-up period of 2.5 years, hypertension (HTP, 34%; NTP, 1%; P < .001) and metabolic syndrome (HTP, 25%; NTP, 5%; P < .001) were more prevalent in HTP women compared with NTP women. HTP women had significantly higher systolic and diastolic blood pressure, higher body mass index, and higher waist circumference. Glucose, glycosylated hemoglobin, insulin, homeostatic model assessment score, total cholesterol, triglycerides, and high-sensitivity C-reactive protein levels were significantly higher and high-density lipoprotein cholesterol was significantly lower in HTP women. CONCLUSION: In women with a history of HTP, hypertension and metabolic syndrome are more common, and they have higher levels of biochemical cardiovascular risk factors 2.5 years after pregnancy.

Biochemical cardiovascular risk factors after hypertensive pregnancy disorders: a systematic review and meta-analysis.

The objective of this study was to perform a systematic review and meta-analysis of studies assessing biochemical cardiovascular risk factors in women with previous hypertensive pregnancy disorders and women with previous normotensive pregnancies. Data were collected from PubMed and EMBASE (from inception to February 28, 2011) supplemented by manual searches of bibliographies. Included were cohort studies and case-control studies assessing biochemical cardiovascular risk factors in women with previous hypertensive pregnancy disorders compared with women with previous normotensive pregnancies. Of 2573 studies reviewed for eligibility, quality, and data extraction, 22 were included in the review, of which 15 could be meta-analyzed. The pooled mean differences for the outcomes of interest were 0.17 mmol/L (95% confidence interval [CI], 0.08-0.25 mmol/L) for glucose (10 studies), 3.46 mU/mL (95% CI, 2.34-4.58 mU/mL) for insulin (5 studies), 0.13 mmol/L (95% CI, 0.05-0.21) for triglycerides (10 studies), 0.22 mmol/L (95% CI, 0.11-0.33 mmol/L) for total cholesterol (11 studies), -0.11 mmol/L (95% CI, -0.18 to -0.04 mmol/L) for high-density lipoprotein cholesterol (10 studies), and 0.21 mmol/L (95% CI, 0.10-0.32) for low-density lipoprotein cholesterol (9 studies), all in the disadvantage in women with previous hypertensive pregnancy disorders. Analyses for preeclampsia alone showed similar results. CONTINUED LEARNING OBJECTIVES: After completing this CME activity, physicians should be better able to assess the long-term cardiovascular consequences after hypertensive pregnancy disorders, evaluate and interpret the evidence regarding biochemical cardiovascular risk factor assessment after pregnancy, and counsel women with a history of hypertensive pregnancy disorders as to the effectiveness of cardiovascular risk factor assessment in the primary prevention of cardiovascular disease. CONCLUSIONS: Women with previous hypertensive pregnancy disorders have higher glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels measured after pregnancy compared with women with previous normotensive pregnancies. These biochemical cardiovascular risk factors may identify women who will benefit from primary prevention of cardiovascular disease. TARGET AUDIENCE: Obstetricians and gynecologists, family physicians.

10-Year cardiovascular event risks for women who experienced hypertensive disorders in late pregnancy: the HyRAS study.

BACKGROUND: Cardiovascular disease is the cause of death in 32% of women in the Netherlands. Prediction of an individual's risk for cardiovascular disease is difficult, in particular in younger women due to low sensitive and specific tests for these women. 10% to 15% of all pregnancies are complicated by hypertensive disorders, the vast majority of which develop only after 36 weeks of gestation. Preeclampsia and cardiovascular disease in later life show both features of "the metabolic syndrome" and atherosclerosis. Hypertensive disorders in pregnancy and cardiovascular disease may develop by common pathophysiologic pathways initiated by similar vascular risk factors. Vascular damage occurring during preeclampsia or gestational hypertension may contribute to the development of future cardiovascular disease, or is already present before pregnancy. At present clinicians do not systematically aim at the possible cardiovascular consequences in later life after a hypertensive pregnancy disorder at term. However, screening for risk factors after preeclampsia or gestational hypertension at term may give insight into an individual's cardiovascular risk profile. METHODS/DESIGN: Women with a history of preeclampsia or gestational hypertension will be invited to participate in a cohort study 2 1/2 years after delivery. Participants will be screened for established modifiable cardiovascular risk indicators. The primary outcome is the 10-year cardiovascular event risk. Secondary outcomes include differences in cardiovascular parameters, SNP's in glucose metabolism, and neonatal outcome. DISCUSSION: This study will provide evidence on the potential health gains of a modifiable cardiovascular risk factor screening program for women whose pregnancy was complicated by hypertension or preeclampsia. The calculation of individual 10-year cardiovascular event risks will allow identification of those women who will benefit from primary prevention by tailored interventions, at a relatively young age. TRIAL REGISTRATION: The HYPITAT trial is registered in the clinical trial register as ISRCTN08132825.