| dc.description.abstract | The aim of this thesis was to investigate the effect of antihypertensive therapy
on vascular function and placental markers in hypertensive disorders in
pregnancy (HTD). We prospectively studied 208 women at the Homerton and
University College London Hospitals. Vascular and serum markers were
measured in 80 with HTD [51 pre-eclampsia (PE), 29 gestational hypertension
(GH)] and 80 normotensive controls. The same markers were measured in
placental samples from another 48 women (14 PE, 10 GH, 24 controls).
Pulse wave analysis indices [augmentation pressure (AP) and augmentation
index at heart rate 75/minute (Aix-75)], serum and placental concentrations of
soluble fms-like tyrosine-kinase-1 (sFlt-1), soluble endoglin (sEng), placental
growth factor (PIGF), vascular endothelial growth factor (VEGF), inhibin A,
activin A, and uterine artery Doppler were measured before, and 24-48 hours
after, initiating antihypertensive therapy. The three study groups were
compared using ANOVA multiple comparisons with Bonferroni post hoc
testing. Marker levels before and after antihypertensives were compared
using paired t-test.
In both pre-eclampsia (P<0.0001) and gestational hypertension
(P<0.05), serum sFlt-1 was increased and PIGF reduced (P<0.001) compared
to controls. Serum sEng levels were also increased in pre-eclampsia.
Placental sFlt-1 and sEng were significantly higher (P<0.0001), and PIGF
lower (P = 0.008), in pre-eclampsia compared to controls and gestational
hypertension. Antihypertensive therapy was associated with a significant fall
in serum and placental sFlt-1 and sEng in pre-eclampsia only (P<0.05). In
pre-eclampsia, but not gestational hypertension, treatment was associated
with significantly (P< 0.05) lower serum and placental inhibin A and activin A.
In women with pre-eclampsia or gestational hypertension, both AP (P<0.0001
and P<0.05) and Aix-75 (P<0.0001 and P<0.001) were significantly higher
than controls. Antihypertensive therapy resulted in a significant fall in both AP
and Aix-75 in pre-eclampsia only (P<0.0001).
Anti hypertensive drugs may have an effect on the pathophysiology of
pre-eclampsia other than their known anti hypertensive action | en_US |
