title: Assessment of cardiovascular risk in women with a history of pre-eclampsia
Creators: name: Brown, Catriona Elizabeth
Publisher: name: University of Glasgow
Year: 2018
Subjects: subject: Cardiovascular risk, pre-eclampsia.

description: Pre-eclampsia is an important and serious condition affecting 2-8% of pregnancies worldwide and carries with it significant associated risk of morbidity and mortality for both mother and child. It is characterised by new onset hypertension after the 20th week of gestation with accompanying proteinuria. Resolution of symptoms should occur following delivery.
Several pathophysiological mechanisms are common to both pre-eclampsia and cardiovascular disease, and the link between pre-eclampsia and cardiovascular disease later in life has been established. While the underlying pathophysiological mechanisms of pre-eclampsia are complex, endothelial dysfunction is a key component. Increased arterial stiffness and hypertension have also been documented. Endothelial dysfunction has been shown to extend beyond childbirth, into the postpartum period. Studies evaluating endothelial dysfunction at even longer time-points following an affected pregnancy have produced conflicting results. Results from biomarker studies have supported the concept of endothelial dysfunction throughout pregnancy and the postpartum period, but as more time elapses between index pregnancy and biomarker sampling, these results also vary. Cardiac imaging and electrocardiographic studies have also contributed to knowledge about the normal physiology of pregnancy and changes which are associated with hypertensive disorders of pregnancy during pregnancy, the postpartum period and beyond. 
The main focus of this thesis was to investigate the possible mechanisms behind the link between pre-eclampsia and future cardiovascular disease. The aim was to investigate women who were free from cardiovascular disease for any evidence of subclinical vascular damage long-term following a pre-eclamptic pregnancy. Overall women recruited to this study would be older than women who participated in the majority of previously published studies on this theme. 
Before embarking on the investigation of subclinical vascular damage in women with a history of pre-eclampsia, a link was confirmed between a history of pre-eclampsia and cardiovascular disease up to 30 years from time of index pregnancy. This was accomplished using record-linkage in a large Scottish cohort; the Generation Scotland Family Health Study (GS:SFHS). Following on from this, ECGs available in women with and without a remote history of pre-eclampsia in the GS:SFHS cohort were assessed for any obvious differences. There was a more leftward shift in the QRS-axis in these women and a trend towards a longer corrected QT interval (QTc) which approached statistical significance, but after adjusting for other co-variates, pre-eclampsia did not independently predict QTc. Investigations for subclinical vascular damage were carried out by means of non-invasive vascular function studies in women recruited from three different cohorts (blood pressure clinics, GS:SFHS and the previous Proteomics in Pre-eclampsia (PIP) study of women during pregnancy). Time since index pregnancy varied between 1-30 years. Flow-mediated dilatation (FMD) was performed to assess for endothelial dysfunction, pulse wave analysis (PWA) and pulse wave velocity (PWV) assessed arterial stiffness, and carotid ultrasound was performed to establish whether there was any evidence of atherosclerosis. After adjusting for other co-variates, I was able to demonstrate the presence of endothelial dysfunction many years after pregnancy in women with a history of pre-eclampsia in comparison with those who experienced a normotensive pregnancy. There was also a significantly higher presence of carotid plaque in women with a history of pre-eclampsia. To investigate whether the findings from the vascular study translated to findings in biomarker studies of women with a history of pre-eclampsia in comparison with controls, samples from the vascular studies cohort and from the wider GS:SFHS cohort were used. Markers of inflammation, angiogenesis, cardiac damage and collagen turnover were studied. A significantly higher vascular endothelial growth factor (VEGF) was detected in women with a history of pre-eclampsia. 
Pre-eclampsia is associated with an increased risk of cardiovascular disease, and endothelial dysfunction is evident later on in life. Larger studies are required to further investigate the vascular and biomarker results, and studies including more thorough cardiac assessment (such as echocardiography) in this population should also be considered. The studies described found no evidence of one single component to explain the relationship between pre-eclampsia and cardiovascular disease later in life. This is not unexpected as pre-eclampsia is a complex condition with multiple contributing factors and it is likely that the increased cardiovascular risk later in life is likewise multifactorial in origin.