Angela H.E.M. Maas

Red alert for women's heart: the urgent need for more research and knowledge on cardiovascular disease in women

A recent report of the EuroHeart project has shown that women are still underrepresented in many cardiovascular clinical trials, while important gender differences are present within most areas of heart disease. As the burden of cardiovascular disease is increasing in middle-aged women relative to men, a more profound understanding is needed of the fundamental biological differences that exist between men and women. In the current review, we aim to address the need for more explanatory sex-specific cardiovascular research to be able to adapt existing guidelines for a better heart health in women.

Is the difference in outcome between men and women treated by primary percutaneous coronary intervention age dependent? Gender difference in STEMI stratified on age

Aim: Poorer outcomes in women with ST-elevation myocardial infarction (STEMI) are often attributed to gender differences in baseline characteristics. However, these may be age dependent. We examined the importance of gender in separate age groups of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). Methods and results: Data of 6746 consecutive patients with STEMI admitted for PPCI between 1998 and 2008 in our hospital were evaluated. Age was stratified into two groups, <65 years (young group) and ≥65 years (elderly). Endpoints were enzymic infarct size as well as 30-day and 1 year mortality. We studied a total of 4991 (74.0%) men and 1755 (26.0%) women; 40% of women were <65 years and 60% of men were <65 years of age. In the elderly group (≥65 years), women had more frequently diabetes and hypertension while they smoked less frequently than men. Younger women smoked more often than similarly aged men and had more hypertension. At angiography, single-vessel disease and TIMI 3 flow before PPCI was more present in younger women than men, whereas these differences were not found in the older age group. Patient delay before admission was shorter in men at all ages, while women had lower creatine kinase levels. Younger women had a higher mortality after 30 days (HR 2.1, 95% CI 1.3−3.4) and at 1 year (HR 1.7, 95% CI 1.2−2.6), whereas in the older age group women mortality rates were higher at 30 days (HR 1.5, 95% CI 1.1−2.0) but not at 1 year (HR 1.2, 95% CI 0.9−1.5). After multivariate analysis, 1-year mortality remained significantly higher in women at younger age (HR 1.7, 95% CI 1.1−2.5). Patient delay before admission was shorter in men in both age groups. Creatine kinase levels were in both age groups higher in men. Conclusions: Differences in mortality between men and women with STEMI treated with PPCI are age dependent. Although young women have less obstructive coronary artery disease and more often TIMI 3 flow before PCI (suggesting a lower risk), survival was worse compared to similarly aged men. Women had a longer patient delay compared to men, but this was not related to gender-specific mortality.

Cardiovascular risk factors in women 10 years post early preeclampsia: the Preeclampsia Risk EValuation in FEMales study (PREVFEM).

Introduction: Preeclampsia is a complication of pregnancy and a known risk factor for cardiovascular disease (CVD) later in a women’s life. The best approach for prevention of CVD in affected young women is yet unclear. We sought to investigate the prevalence of cardiovascular risk factors in women at 10 years post preeclampsia in comparison with a reference group. Methods: Women with a history of early preeclampsia (exposed), DBP ≥90 mmHg with proteinuria ≥0.3gram/24 h before 32 weeks of gestation, and an equal number of women after uncomplicated pregnancy (non-exposed) from the obstetric database of 1991–2007, were sent a questionnaire and invited for a cardiovascular screening programme. Results: The current study included 339 exposed women and 332 non-exposed women, 10 years post index-pregnancy. Systolic and diastolic blood pressures (SBP/DBP) were 127/86 mmHg versus 119/79 mmHg in the exposed and reference group respectively (p < 0.001). Exposure to early preeclampsia was associated with a threefold increased prevalence of hypertension (adjusted odds ratio (OR) 3.59, 95%CI 2.48–5.20). BMI and waist circumference were 26.9 kg/m2 and 86.5 cm in the exposed group and 26.2 kg/m2 (p = 0.07) and 83 cm (p = 0.001) in the non-exposed group. We found no differences in levels of glucose, lipids and CRP. Adjusted OR for the metabolic syndrome in women post preeclampsia was 2.18 (95% CI 1.34–3.52) compared with women in the reference group. Conclusion: We found a high prevalence of hypertension in young women at 10 years post early preeclampsia. More research on the timing of cardiovascular screening in these high-risk women is needed.

Preeclampsia as a female-specific risk factor for chronic hypertension

Preeclampsia is a complication of pregnancy that has also long term effects on maternal health. Several epidemiologic studies have shown an increased risk for cardiovascular morbidity (relative risk [RR] 2.3) and mortality (RR 2.3) in women after a history of preeclampsia. The chance to develop chronic hypertension afterwards is twofold to 10 times higher in affected women, compared with women after normotensive pregnancies. As hypertension is a major cardiovascular risk factor, early detection and treatment is mandatory to reduce the risk of future cardiovascular disease. Data on (cost)-effectiveness of cardiovascular screening programs in women after preeclampsia are currently lacking and there are no recommendations yet for prevention in the guidelines. We recommend regularly preventive blood pressure measurements after high risk pregnancies. More research is needed to identify women who will profit most of early intervention.

Determinants of future cardiovascular health in women with a history of preeclampsia

Women who develop preeclampsia have an increased risk of cardiovascular disease (CVD) later in life. However, current guidelines on cardiovascular risk assessment and prevention are unclear on how and when to screen these women postpartum, and about the role of a positive history of preeclampsia in later-life CVD risk management. The aim of this review is to discuss the present knowledge on commonly used cardiovascular screening modalities available to women with a history of preeclampsia, and to discuss recent developments in early detection of CVD using cardiovascular imaging. Furthermore, we explore how female-specific risk factors may have additional value in cardiovascular screening, in particular in relatively young women, although their implementation in clinical practice is challenged by inconsistent results and lack of long-term outcome data. Non-invasive imaging techniques, e.g., coronary artery intima-media thickness (CIMT), can be helpful to detect subclinical atherosclerotic disease, and coronary artery calcium scoring (CACS) has shown to be effective in early detection of cardiovascular damage. However, while more short-term and long-term follow-up studies are becoming available, few studies have investigated women with a history of preeclampsia in the fourth and fifth decade of life, when early signs of premature CVD are most likely to become apparent. Further studies are needed to inform new and improved clinical practice guidelines, and provide long-term strategies to effectively prevent CVD, specifically targeted at women with a history of preeclampsia. Additionally, evaluation of feasibility, cost-effectiveness, and implementation of CVD screening and prevention initiatives targeted at former preeclampsia patients are needed.

Serum AMH Levels in Women With a History of Preeclampsia Suggest a Role for Vascular Factors in Ovarian Aging

CONTEXT The association between early menopause and vascular disease as a possible causative factor has recently received attention. Preeclampsia (PE) is associated with future cardiovascular risk factors, and this premature vascular aging potentially modifies the ovarian aging process. OBJECTIVE The purpose of this study was to assess whether women with a history of PE have lower anti-Müllerian hormone (AMH) levels than women with normotensive pregnancies. DESIGN This was a retrospective cohort study. SETTING The study was conducted in a tertiary referral center. PATIENTS Clinical data and blood samples of participants in the Preeclampsia Risk EValuation in FEMales study were used (336 women with a history of PE and 329 women after a normotensive pregnancy). INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURES The relative decrease in AMH levels was assessed after a median follow-up of 10.5 years. RESULTS The mean AMH level was 2.00 ± 1.87 μg/L in the PE group compared with 2.26 ± 2.56 μg/L in the reference group. Linear regression analysis with censoring for undetectable AMH levels, adjusted for age, smoking, and hormonal contraceptive use, showed a relative reduction in AMH levels of 20.9% at any age (fold change 0.79, 95% confidence interval, 0.67-0.94). CONCLUSIONS We demonstrate that women with a history of PE have significantly lower AMH levels than women with normotensive pregnancies. Calculations based on a reference population indicate advancement of reproductive age of approximately 1.5 years. Because PE is considered a manifestation of impaired vascular health, these results support the hypothesis that compromised vascular health could act as a causative mechanism in early ovarian aging.

Cardiovascular risk management after reproductive and pregnancy-related disorders: A Dutch multidisciplinary evidence-based guideline

Background 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 standardised follow-up of these women becausee 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. Therefore, the Dutch Society of Obstetrics and Gynaecology initiated a multidisciplinary working group to develop a guideline for cardiovascular risk management after reproductive and pregnancy-related disorders. Methods 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 captured by systematic review. Recommendations for clinical practice were formulated based on the evidence and consensus of expert opinion. The Dutch societies of gynaecologists, cardiologists, vascular internists, radiologists and general practitioners reviewed the guideline to ensure support for implementation in clinical practice. Results For all reproductive and pregnancy-related disorders a moderate increased relative risk was found for overall CVD, except for preeclampsia (relative risk 2.15, 95% confidence interval 1.76–2.61). Conclusion Based on the current available evidence, follow-up is only recommended for women with a history of preeclampsia. For all reproductive and pregnancy-related disorders optimisation of modifiable cardiovascular risk factors is recommended to reduce the risk of future CVD.

BRCA1/2 mutation carriers are potentially at higher cardiovascular risk

BRCA1/2 mutation carriers have an elevated risk of developing breast and ovarian cancer at a relatively young age. Risk-reducing salpingo-oophorectomy is an established strategy to tremendously reduce the risk of ovarian cancer. It is recommended to perform this surgery at age 35-40 years (BRCA1) and at age 40-45 years (BRCA2) resulting in an early and abrupt menopause. BRCA1/2 mutation carriers are potentially at higher risk of cardiovascular diseases due to early surgical menopause, and cardiotoxic effects of adjuvant treatment for breast cancer. Furthermore, preliminary results of experimental studies suggest a possible causative function of the BRCA genes in cardiovascular risk. More research on cardiovascular health risks in BRCA1/2 mutation carriers is needed, especially in the field of cardio-oncology, requiring additional attention to potentially cumulative effects on cardiovascular risks in this specific group of women.

Longitudinal analysis of cardiovascular risk parameters in women with a history of hypertensive pregnancy disorders: the Doetinchem Cohort Study

Women with hypertensive pregnancy disorders (HPD) are at increased risk of developing hypertension and cardiovascular disease later in life; however, it is not known how cardiovascular risk develops throughout life. We evaluated the longitudinal trends in cardiovascular risk factors in women after hypertensive pregnancy disorders compared with women with normotensive pregnancies.

Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy

A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained.