We used the data linkage of two well validated datasets to allow us to robustly identify cardiovascular events by inpatient admission. This linkage allowed us to characterise our cohort in detail and analyse their maternity data.

In the GS:SFHS cohort women with a history of preeclampsia had a higher blood pressure and greater risk of cardiovascular events later in life than women with normotensive pregnancies. Women with a history of preeclampsia experienced earlier gestational age at delivery and were more likely to have a caesarean section birth. On survival analysis, women with a history of preeclampsia were more likely to have cardiovascular events later in life than women with normotensive deliveries. The women in our study were within 33 years of pregnancy with a mean age of 53 years in the PE cardiovascular events group. Although our study only had a small number of 25 women who had a cardiovascular event after preeclamptic pregnancy these results are consistent with other studies. A 2017 meta-analysis of 22 studies and >2,500,000 women showed the risk for cardiovascular event was highest 1 to 10 years postpartum, supporting our data that adverse cardiac events may occur before middle age [6, 10]. Close follow up in the years postpartum even in a young cohort with focus on preventative medicine may help to reduce the cardiovascular risk in this group.

Nulliparous women were found to have a greater risk of cardiovascular events than parous women. We were unable to differentiate nulliparous women who chose not to have children from those who could not become pregnant within our cohort. This higher risk associated with nulliparity may therefore reflect the relationship between general health and fertility. The nulliparous group had a significantly higher BMI, blood pressure and higher proportion of hypertension than our parous group. However, our findings are supported by other studies reporting increased cardiovascular risk associated with nulliparity [11, 12]. To examine the impact of parity future studies should try to differentiate nulliparous women who chose to not become pregnant and those who could not become pregnant, as combining these groups may falsely attribute nulliparity to greater cardiovascular risk or mask an even higher risk within subgroups of the nulliparous population.

The strength of this study was in using the ICD classification and SMR01 and SMR02 data. This does not depend on recall of participants and is therefore not subject to this bias. The ISD data undergoes quality assessment, and rigorous exclusion of any pregnancy which was not deemed preeclampsia was carried out. Exclusion of any non-normotensive pregnancy was also applied to the control group. Cardiovascular events were evaluated in nulliparous women in addition to those with preeclampsia and normotensive pregnancies.

A limitation of this study is that only women who had lived long enough to enrol in the Generation Scotland study were included, some women who exhibited cardiovascular events earlier and suffered cardiovascular mortality are therefore not included. The women who were participants in Generation Scotland may have been more interested than average in their own health and general fitness and wellbeing, so therefore may not be fully representative of the Scottish population. Due to sample size, it was not possible to assess the effect of recurrent preeclampsia or to compare women with multiple to single pregnancies. We are aware of different severity and possible prognostic differences between the early and late PE. For our study, differentiating between early and late PE was not possible. These limitations have wider implications on the robustness of our adjustments particularly in survival analysis. Different exposures of cases and controls to risk and disease factors at selection and during follow-up should ideally be taken into account but with our focus on cardiovascular events, time-varying models to take changes and differences in exposure into account were not possible.

Women with a history of PE have been recognised to have an increased risk of long-term cardiovascular events including heart failure, coronary artery disease, and stroke [3,4,5,6,7, 10, 13,14,15]. The Cardiovascular health after maternal placental syndromes (CHAMPS) population-based cohort study looked at 1.03 million women, free from cardiovascular disease before their first documented delivery, between 1990 and 2004 enrolled in the Ontario Health Insurance Plan, which holds all maternity data [7]. To analyse outcomes, the data was linked to the mortality data from the Canadian Registered Persons Database and to hospital admissions data from Canadian Institute for Health Information Discharge Abstract Database. The primary outcome was a composite of cardio-vascular disease, defined as hospital admission for coronary, cerebrovascular, or peripheral artery disease, or revascularisation of the coronary, carotid, or a lower extremity arterial system [7]. The median duration of follow-up was 8·7 years. The preeclampsia group (n = 36982) showed an increased risk of premature cardiovascular disease (HR2·1 CI 1·8–2·4) with an average age of 38 years at their first cardiovascular event [7].

This study gives further evidence to the need for early postpartum and long term follow up for women with a history of PE [6, 10, 13, 15,16,17,18,19,20,21]. There is a need for identification of biomarkers with a strong predictive value of future postpartum CVD in women with a history of PE [22]. Increased levels of angiogenic factors such as soluble endoglin and increased ratios of soluble Fms-like tyrosine kinase 1: placental growth factor have been identified as clinically useful predictive and diagnostic biomarkers in the development of preeclampsia however to date no specific markers for future CVD risk has been identified [23]. Biophysical markers such as pulse wave velocity, flow mediated dilatation and carotid intima-media thickness should also be explored as a possible predictive tool of future CVD risk [24]. If biomarkers could be identified then resources could be personalised and targeted towards those most at risk of future CVD. This presents an important avenue for future research in this field.

Currently guidelines around timing of follow up, cardiovascular screening and preventive strategies for cardiovascular disease in the cohort who have history of previous preeclampsia vary worldwide and consensus is lacking. There is an urgent need for uniform guidelines and implementation to improve the health in this cohort. Increased awareness among the public of the cardiovascular risk associated with PE is vital to aid uptake of cardiovascular prevention programmes.

While outside the scope of this study, there is increased recognition of the increased CVD risk experienced by the offspring of women with a history of PE [22, 23, 25,26,27]. Future research into this important aspect of this topic and guidelines surrounding CVD risk prevention in the offspring of this cohort may also be warranted.