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Title: Microvascular circulation in pregnancy-associated hypertensive disorders
Author: Nama, Vivek
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2013
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Preeclampsia (PE) is the commonest hypertensive disorder seen in pregnancy and is a significant cause for maternal mortality and morbidity world wide. Its impact on perinatal morbidity and mortality is difficult to measure. It is a well known fact that women who develop PE are at an increased risk of essential hypertension and other cardiovascular mortality like stroke and heart attacks. Recent literature has suggested that women who develop PE have increased markers of cardiovascular disease at the time of booking their pregnancy. We have previously demonstrated that reduction in capillary density after venous congestion (Structural capillary rarefaction) is an early marker for essential hypertension. We hypothesized that structural capillary rarefaction could be an early marker for PE. We aim to measure capillary density in primigravid Caucasian women with no other complications (low risk group) and in women with previous PE and Essential hypertension (high risk group). We measured fasting blood sugar, fasting insulin, fasting lipid profile at booking, VEGFR2 (angiogenic), sFlt-1 (antiangiogenic) and Endoglin (anti-angiogenic) factors along with their routine blood tests (11-16 weeks, 27-32 weeks, 34-38 weeks). Our objective was to find if capillary rarefaction existed before the onset of PE and if acted as a mediator of this syndrome, if so could it be used to predict PE either as a stand alone marker or in combination with other known predictive factors measured in this study. We recruited 326 subjects to participate in the study to measure capillary density at 11-16 weeks, 20-24 weeks, 28-31 weeks, 34-38 weeks and 5-15 weeks postnatally. After 150 women were followed up for all 5 visit and a normogram of capillary density changes in pregnancy was established, we selectively followed up women who had a uterine artery pulsatality index of < 2.5 at 21 weeks scan as they were low risk of developing PE. 15 women were lost for follow up and 5women were excluded because of violation of the protocol. 1 pregnancy was terminated for a foetal anomaly. A total of 305 women were analyzed. At the initial analysis it was found that capillary rarefaction occurred at 20 weeks in women who later developed preeclampsia. We measured VEGFR2 an endothelial progenitor cell marker involved in neoangiogenesis of capillaries. We also measured anti-angiogenic factors sFlt-1 and Endoglin in a cohort of women in the normotensive group at random and all the samples in the PE group. We found that capillary density at baseline and after venous congestion decreases as pregnancy progresses in normal pregnancy. In women who develop Preeclampsia the magnitude of decrease in capillary density at baseline and after venous congestion is exaggerated and is earlier compared to women who remained normotensive. The changes in anti-angiogenic factors are also exaggerated when compared to normal pregnancy. The VEGFR2 levels are lower at 34-38 weeks visit in women who had term preeclampsia when compared to normotensive women. Structural rarefaction of skin capillaries at 20-24 weeks gestation and 27-32 weeks gestation were reliable predictors of preeclampsia. Combining capillary rarefaction with uterine artery doppler pulsatility index can further increase the sensitivity and specificity of the prediction. We also confirmed that previous history of preeclampsia or chronic hypertension and high UAD pulsatility index were independent predictors of preeclampsia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available