Abstract P043: Preeclampsia Superimposed On Chronic Hypertension: Evidence For A Hormone-mediated, Lasting Effect On Antihypertensive Needs

Abstract

Objective: To characterize clinical and molecular differences between chronic hypertension (HTN), preeclampsia superimposed on chronic hypertension (SI), and isolated pregnancy induced hypertension (PIH). Methods: Individuals with HTN, SI, or PIH who had a livebirth between 2017 and 2020 were identified in an obstetric biorepository. Medical histories were reviewed. Paraffin-embedded placental samples (N=36; N HTN =13, N SI =7, N PIH =16) were submitted for bulk RNA sequencing along with matched non-hypertensive controls (N=12). Differential gene expression was assessed for the HTN, SI, and PIH samples relative to the controls; transcripts with significant differences (P adj <0.05) underwent Gene Ontology analysis. Results: Chronic hypertension was present in 28.6% (N=40/140) of the sample; 37.5% (N=15/40) developed SI. Those with SI were more likely to require additional peripartum antihypertensive therapy than with those with PIH (P<0.01). They also had lower rates of antihypertensive down-titration or discontinuation at 6 weeks postpartum (P=0.01). Placental samples demonstrated a hormone-mediated mechanism for these differences with gonadotropin secretion and regulation differences in the transcriptomic signature of SI. Growth factors and mediators of placental development were differentially expressed in HTN and PIH (Figure 1). Conclusion: SI has longer-lasting effects on hypertension trajectory than PIH. Placentally mediated differences in sex hormone dysregulation may underlie clinical differences in antihypertensive needs. Figure 1 Gene ontology results with Bonferroni-corrected significance threshold.