Abstract 9: The Vasopressin Pro-Segment Copeptin

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Abstract

Preeclampsia (PreE) is a unique late-gestational hypertensive disorder that affects 5-7% of all pregnancies and causes a disproportionate percentage of all perinatal morbidity and mortality. The prediction, prevention, modeling, and subsequent management of PreE have been severely limited by the lack of a known central etiology. Although placental dysfunction is considered the major mediator of PreE, many upstream and downstream vascular, immunologic, and hormonal mechanisms have been implicated in its cause. Vasopressin plays an important role in the maintenance of vascular tone in populations affected by low-renin hypertension such as African-Americans, the elderly, and those with chronic heart and renal failure. PreE is also a relatively low-renin hypertension state (vs. normotensive pregnancy), leading us to hypothesize a role for vasopressin in PreE. Copeptin (CP) is a stable 4 kDa pro-segment of vasopressin and secreted in a 1:1 molar ratio, thereby making CP an ideal biomarker of vasopressin secretion. Utilizing maternal plasma from the prospectively collected, IRB-approved Maternal Fetal Tissue Bank at the University of Iowa, CP was measured throughout pregnancy using a commercially available ELISA. Maternal plasma CP was significantly elevated in all trimesters in pregnancies that eventually developed PreE (n=50) versus (n=31) controls (1st trimester: 903±138 vs. 2045±371 pg/mL, p=0.03; 2nd trimester: 672±95 vs. 1754±37, p=0.05; 3rd trimester: 829±72 vs. 1832±247, p=0.002). After controlling for covariates such as age, BMI, chronic hypertension, twin gestation, diabetes, and history of PreE, the association of an elevated CP and the development of preeclampsia remains significant. ROC analyses reveal that CP is significantly predictive of the development of preeclampsia in all trimesters. Notably, these data establish CP as a novel, potent, 1st trimester predictor of PreE (AUC=0.80, p=0.005, at a cutoff of 1258 pg/mL). The temporal order of changes in CP (1st trimester) versus other known mechanisms of PreE (late pregnancy) supports our working hypothesis that vasopressin secretion may precipitate or induce other known humoral, vascular, immune, and morphological mechanisms of PreE.

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