Prospective study of placental angiogenic factors and maternal vascular function before and after preeclampsia and gestational hypertension.
BACKGROUND
Preeclampsia is a life-threatening pregnancy syndrome of uncertain origin. To elucidate the pathogenesis, we evaluated the temporal relationships between changes in vascular function and circulating biomarkers of angiogenic activity before and after the onset of preeclampsia and gestational hypertension.


RESULTS
Maternal mean arterial pressure, uterine artery pulsatility index, brachial artery flow-mediated dilatation, and serum concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin were prospectively measured in 159 women from 10 weeks gestation until 12 weeks postpartum. At 10 to 17 weeks, women who developed preterm preeclampsia had lower serum PlGF (P=0.003), higher soluble endoglin (P=0.006), and higher sFlt-1:PlGF ratio (P=0.005) compared with women who later developed term preeclampsia, gestational hypertension, or normotensive pregnancy. At 10 to 17 weeks, mean arterial pressure inversely correlated with serum PlGF (r=-0.19, P=0.02); at 18 to 25 weeks, with soluble endoglin (r=0.18, P=0.02); and at 26 to 33 weeks, with sFlt-1 (r=0.28, P<0.001). At 23 to 25 weeks, uterine artery pulsatility index correlated with serum soluble endoglin (r=0.19, P=0.02) and sFlt-1 levels (r=0.17, P=0.03). Flow-mediated dilatation was higher during a pregnancy with gestational hypertension compared with preeclampsia (P=0.001). Twelve weeks postpartum, serum PlGF was higher in women who had a hypertensive pregnancy compared with a normotensive pregnancy (P<0.001).


CONCLUSIONS
These observations support a role for placenta-derived angiogenic biomarkers in the control of maternal vascular resistance of preeclampsia. Gestational hypertension develops differently, with a hyperdynamic circulation and angiogenic biomarker profile similar to normotensive pregnancy. Larger studies of unselected women are needed to ascertain whether measures of these angiogenic biomarkers assist with the prediction and prognosis of preeclampsia and whether postpartum measures of serum PlGF have a role in predicting future cardiovascular disease.
Noori
Muna
M
Division of Surgery, Imperial College, Chelsea and Westminster Hospital, London, UK.
Donald
Ann E
AE
Angelakopoulou
Aspasia
A
Hingorani
Aroon D
AD
Williams
David J
DJ
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000502:physiology; D000071063:Endoglin; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood* / Q000453:epidemiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood* / Q000453:epidemiology; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D011257:Pregnancy Proteins / Q000097:blood; D011446:Prospective Studies; D011673:Pulsatile Flow / Q000502:physiology; D011956:Receptors, Cell Surface / Q000097:blood; D012307:Risk Factors; D055988:Uterine Artery / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1