Background: Reproductive disorders, such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and hypertensive pregnancy disorders (HPD) like pre-eclampsia (PE), are associated with an increased risk of cardiovascular disease (CVD). Detection of early signs of cardiovascular disease (CVD), as well as identification of risk factors among women of reproductive age which improve cardiovascular risk prediction, is a challenge and current models might underestimate long-term health risks. The aim of this study is to assess cardiovascular disease in patients with a history of a reproductive disorder by low-dose computed tomography (CT). Methods: Women of 45-55years, who experienced a reproductive disorder (PCOS, POI, HPD), are invited to participate in this multicenter, prospective, cohort study. Women will be recruited after regular cardiovascular screening, including assessment of classical cardiovascular risk factors. CT of the coronary arteries (both coronary artery calcium scoring (CACS), and contrast-enhanced coronary CT angiography (CCTA)) and carotid siphon calcium scoring (CSC) is planned in 300 women with HPD and 300 women with PCOS or POI. In addition, arterial stiffness (non-invasive pulse wave velocity (PWV)) measurement and cell-based biomarkers (inflammatory circulating cells) will be obtained. Discussion: Initial inclusion is focused on women of 45-55years. However, the age range (40-45years and/or ≥55years) and group composition may be adjusted based on the findings of the interim analysis. Participants can potentially benefit from information obtained in this study concerning their current cardiovascular health and expected future risk of cardiovascular events. The results of this study will provide insights in the development of CVD in women with a history of reproductive disorders. Ultimately, this study may lead to improved cardiovascular prediction models and will provide an opportunity for timely adjustment of preventive strategies. Limitations of this study include the possibility of overdiagnosis and the average radiation dose of 3.5mSv during coronary and carotid siphon CT, although the increased lifetime malignancy risk is negligible. Trial registration: Netherlands Trial Register, NTR5531. Date registered: October 21st, 2015.

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Keywords Cardiovascular disease, Cardiovascular risk factors, Carotid siphon calcification, Cell-based biomarkers, Coronary artery calcium, CT angiography, Hypertensive pregnancy disorders, Polycystic ovarian syndrome, Primary ovarian insufficiency, Reproductive disorders
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Journal BMC Women's Health
Zoet, G.A. (Gerbrand A.), Meun, C, Benschop, L. (Laura), Boersma, H, Budde, R.P.J, Fauser, B.C.J.M, … Velthuis, B.K. (2017). Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): Rationale and design of a multicenter cohort study. BMC Women's Health, 17(1). doi:10.1186/s12905-017-0415-x