Arterial stiffness and hemodynamic parameters for the early prediction of preeclampsia: a prospective cohort study

Objective: Preeclampsia is a leading complication of pregnancy, yet there remains no reliable clinical tool for its early prediction. Assessment of vascular dysfunction, a central feature of preeclampsia, by arterial stiffness and hemodynamic measurements could be a promising tool for preeclampsia prediction. This study aimed to evaluate 1) arterial stiffness and hemodynamic parameters as an early predictive tool for preeclampsia, and 2) longitudinal changes in these parameters and identify changepoints prior to preeclampsia onset. Design and method: In this prospective longitudinal cohort study of women with singleton high-risk pregnancies (n = 236), arterial stiffness (carotid-femoral pulse wave velocity, cfPWV) and wave reflection (augmentation index [AIx], and time to wave reflection [T1R]) were assessed using applanation tonometry (SphygmoCor, AtCor) at 10–13 weeks and repeated every 4 weeks throughout pregnancy. Circulating angiogenic biomarkers (soluble fms-like tyrosine kinase, and placental growth factor) were measured (Quantikine, R&D Systems) at each trimester, and a bilateral uterine artery Doppler (UAD) was performed in the second trimester. The predictive ability of arterial stiffness was compared to that of peripheral blood pressure, UAD indices, as well as angiogenic biomarkers. Furthermore, changepoints in cfPWV, AIx, and T1R were compared between women who did and did not subsequently develop preeclampsia. Results: A first-trimester 1 m/s increase in cfPWV was associated with 64% increased odds (p < 0.05), while a 1 ms increase in T1R with 11% decreased odds for preeclampsia (p < 0.01). The area under the curve of arterial stiffness, blood pressure, ultrasound indices, and angiogenic biomarkers was 0.84, 0.68, 0.66, and 0.64, respectively (Figure). A changepoint in cfPWV was detected at 14–17 weeks. cfPWV then increased in women who subsequently developed preeclampsia but decreased in women who did not; a 1.2 m/s difference in cfPWV between the groups was observed at 22–25 weeks. An increase in AIx was noted at 18–21 weeks while at 30–33 weeks in women who did and did not develop preeclampsia, respectively. Conclusions: Arterial stiffness and wave reflection were higher in the first trimester and throughout pregnancy in women destined to develop preeclampsia. These indices predicted preeclampsia earlier (in the first trimester) and with greater ability than blood pressure, UAD, and/or angiogenic biomarkers. Furthermore, altered vascular adaptations in the early second trimester were observed in women who subsequently developed preeclampsia. These findings demonstrate the potential clinical utility of arterial stiffness and hemodynamic parameters as an early screening tool for preeclampsia, which can be used to inform clinical management of high-risk pregnancies.