Angiogenic Factors in Superimposed Preeclampsia

Abstract

Abstract-Imbalances in circulating angiogenic factors contribute to the pathogenesis of preeclampsia. To characterize levels of angiogenic factors in pregnant women with chronic hypertension, we prospectively followed 109 women and measured soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor at 12, 20, 28, and 36 weeks' gestation and postpartum. Superimposed preeclampsia developed in 37 (34%) and was early onset (Ͻ34 weeks) in 9 and later onset (Ն34 weeks) in 28. Circulating levels of sFlt1 and the ratio of sFlt1 to placental growth factor were higher before clinical diagnosis at 20 weeks' gestation in women who subsequently developed early onset preeclampsia between 28 and 34 weeks compared with levels in women who never developed preeclampsia (Pϭ0.001) or who developed late-onset preeclampsia (Pϭ0.001). Circulating levels of sFlt1, soluble endoglin, and the ratio of sFlt1:placental growth factor were also significantly higher, and placental growth factor levels were significantly lower at the time of clinical diagnosis of superimposed preeclampsia in women with either early or late-onset superimposed preeclampsia compared with levels at similar gestational ages in those with uncomplicated chronic hypertension. We conclude that alterations in angiogenic factors are detectable before and at the time of clinical diagnosis of early onset superimposed preeclampsia, whereas alterations were observed only at the time of diagnosis in women with late-onset superimposed preeclampsia. Key Words: superimposed preeclampsia Ⅲ angiogenic factors Ⅲ chronic hypertension in pregnancy P reeclampsia (PE), a syndrome that manifests in the latter half of pregnancy and is characterized by maternal hypertension and proteinuria, develops in Ϸ3% to 5% of pregnant women. 1 PE may also develop in women with chronic (preexisting) hypertension and occurs 3 to 5 times more frequently compared with women who are normotensive at conception. [2][3][4] The diagnosis of superimposed PE (SPE) is often difficult, because women already have hypertension and some even have proteinuria. SPE is associated with even greater maternal and fetal morbidity and mortality than PE in women without preexisting hypertension. 2,5 The pathogenesis of PE, as well as SPE, is likely to involve placental vascular remodeling, leading to defective placentation, 6,7 placental ischemia, 8,9 and maternal endothelial cell dysfunction. 10 Emerging data suggest that placental ischemia is associated with increased production of placental proteins, which, on release into the maternal circulation, cause maternal systemic inflammation and endothelial cell dysfunction. 11,12 In particular, an imbalance in circulating proangiogenic and antiangiogenic factors released by the hypoxic placenta has gained currency as a critical link between placental dysfunction and several maternal manifestations of PE, particularly endothelial dysfunction and proteinuria. 13 Results from clinical trials suggest that the soluble forms of the vascular endothelial ...

The Promise of Angiogenic Markers for the Early Diagnosis and Prediction of Preeclampsia

“…With this approach, Moore Simas et al studied the high-risk population and achieved excellent diagnostic accuracy, calculating areas under the ROC curve for the sFlt-1/ PlGF ratio as 0.97 and for sFlt-1 as 0.90 for the prediction of early onset preeclampsia. Perni et al demonstrated in a longitudinal study of women with chronic hypertension that alterations in sFlt-1, PlGF, sFlt-1/ PlGF, and sEng were dramatically altered as early as 20 weeks of gestation in women who developed subsequent early onset preecalmpsia (51 ). Results have been more modest in other studies using angiogenic markers in high-risk populations (52,53 ).…”

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

“…Hence, the incorporation of angiogenic markers may help to risk stratify women with high suspicion for preeclampsia. Similarly, angiogenic markers have proved to be useful in distinguishing between confounding diagnoses, such as chronic hypertension, CKD, and lupus nephritis (12)(13)(14)(15). The potential to target sFlt as a therapy is also exciting and currently being studied using an apheresis technique (16).…”

New Developments in the Pathogenesis of Preeclampsia

“…A number of recent studies have suggested that circulating angiogenic factors in plasma or urine can be used to differentiate preeclampsia from other diseases that mimic preeclampsia such as chronic hypertension, gestational hypertension, lupus nephritis and gestational thrombocytopenia [47][48][49][50][51][52][53][54][55][56] . To demonstrate clinical utility, we prospectively studied the role of angiogenic biomarkers in the prediction of preeclampsia related adverse outcomes among women evaluated at our institution for suspected preeclampsia.…”