Prognostic Value of Angiogenic Markers in Pregnant Women With Chronic Hypertension

Abstract

Background Women with chronic hypertension face a 5‐ to 6‐fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms‐like kinase 1 (sFlt‐1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt‐1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension. Methods and Results This retrospective study included 142 women with chronic hypertension and suspected superimposed preeclampsia. Twenty‐seven women (19.0%) delivered because of maternal indications only, 17 women (12.0%) because of fetal indications primarily, and 98 women (69.0%) for other reasons. Women who both delivered because of maternal indications and for fetal indications had a significantly higher sFlt‐1/PlGF ratio (median 99.9 and 120.2 versus 7.3, respectively, P <0.001 for both) and lower PlGF levels (median 73.6 and 53.3 versus 320.0 pg/mL, respectively, P <0.001 for both) compared with women who delivered for other reasons. SFlt‐1/PlGF ratio and PlGF were strong predictors for delivery because of superimposed preeclampsia, whether for maternal or fetal indications ( P <0.05). Half of women with angiogenic imbalance (sFlt‐1/PlGF ratio ≥85 or PlGF levels <100 pg/mL) delivered because of maternal or fetal indications within 1.6 weeks (95% CI, 1.0–2.4 weeks). Conclusions Angiogenic marker imbalance in women with suspected superimposed preeclampsia can predict delivery because of maternal and fetal indications related to superimposed preeclampsia and is associated with a significantly shorter time to delivery interval.

Translation of mechanistic advances in preeclampsia to the clinic: Long and winding road

“…[74][75][76][77] sFlt-1 and PlGF tests are also useful in distinguishing preeclampsia from other confounding diseases such as gestational hypertension, primary renal disease, chronic hypertension, gestational thrombocytopenia, and immune thrombocytopenic purpura. 61,75,76,[78][79][80][81][82][83][84] By specifically identifying preeclampsia, the test can enable earlier diagnosis and targeted treatments.…”

“…72,88,94,102 Several other studies have confirmed the robust predictive performance of these biomarkers. 84,89,[103][104][105][106][107][108][109][110][111][112] Although there was growing evidence that angiogenic biomarkers could also be useful to predict disease progression in a diverse group of patients with suspected preeclampsia 89,[113][114][115][116][117] and in patients hospitalized with a hypertensive disorder of pregnancy, 118 studies in developing countries have been limited. 114 The PRAECIS study (NCT03815110)-among the largest and the most diverse U.S. studies to date with 18 participating centers-analyzed ~1000 pregnant women hospitalized with a hypertensive disorder between 23 and 35 weeks' gestation.…”

“…Using automated assays, several studies have now confirmed that plasma or serum measurements of sFlt‐1 and PlGF have sensitivities and specificities >90% as an aid in the diagnosis of preterm preeclampsia 74–77 . sFlt‐1 and PlGF tests are also useful in distinguishing preeclampsia from other confounding diseases such as gestational hypertension, primary renal disease, chronic hypertension, gestational thrombocytopenia, and immune thrombocytopenic purpura 61,75,76,78–84 . By specifically identifying preeclampsia, the test can enable earlier diagnosis and targeted treatments.…”

Longitudinal assessment of angiogenic markers in prediction of adverse outcome in women with confirmed pre‐eclampsia

“…Recently, maternal serum angiogenic marker imbalance has been acknowledged in several international guidelines as a criterion for diagnosis of PE. Moreover, the maternal serum sFlt-1/PlGF ratio has been shown to be an important tool, not only for the diagnosis of PE in women with suspected PE, but also in the prognosis of the disease; for example, estimating the time until delivery and prediction of adverse maternal and perinatal outcome 2,3,6,7,18,36,40 . Repeat assessment of the ratio is advised in women with suspected PE, with a ratio between 38 and 85 or 110 after 34 weeks' gestation, as well as for the surveillance of high-risk cohorts, such as women with chronic hypertension 7,32 .…”

“…It remains one of the leading causes of maternal and perinatal morbidity and mortality worldwide 1 . Recently, angiogenic marker assessment has revolutionized the prediction and diagnosis of hypertensive disorders of pregnancy [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and has been recommended as a useful tool in several international guidelines [19][20][21] . Compared with conventional diagnostic methods, such as blood pressure measurement and assessment of proteinuria, angiogenic markers show superior predictive accuracy for adverse outcome in pregnancy complicated by PE 15,[22][23][24][25][26][27][28][29][30][31] .…”