THE EFFECT OF ANTI HYPERTENSIVE THERAPY ON HAEMODYNAMIC AND PLACENTAL MARKERS IN HYPERTENSIVE DISORDERS IN PREGNANCY

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