Abstract 041: Elevated Circulating Copeptin in Mid-Gestation is Associated with Increased Aortic Stiffness and Vascular Endothelial Dysfunction in Pregnant Women at High Risk for Preeclampsia
Circulating copeptin, a stable biomarker of vasopressin (AVP) secretion, is elevated throughout pregnancy in women who develop preeclampsia (PreE) and is a strong predictor of PreE as early as the 6th week gestation. Reduced vascular endothelial function and increased aortic stiffness occur in mid-gestation before clinical signs/symptoms of PreE manifest, suggesting that maternal vascular dysfunction may be an early event in the pathogenesis of PreE. However, it is unknown whether elevated copeptin/AVP in early/mid gestation contributes to vascular dysfunction in pregnant women who subsequently develop PreE. Therefore, we hypothesized that elevated copeptin would be associated with increased aortic stiffness and reduced vascular endothelial function in early/mid gestation of pregnant women at high risk for PreE. Pregnant women in the 1st trimester (n=72; age=30 ±1 yrs; BMI=34 ± 1 kg/m2) with at least 1 risk factor for PreE were enrolled. Aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), vascular endothelial function (brachial artery flow-mediated dilation, FMD), blood pressure (BP) and plasma copeptin (ELISA) were assessed in both the 1st (11.7 ± 0.2 wks) and 2nd (18.8 ± 0.4 wks) trimesters. In the 1st trimester, CFPWV (7.3 ± 0.2 vs. 7.3 ± 0.5 m/sec, P=0.86), brachial artery FMD (12.9 ± 1.1 vs. 14.3 ± 2.0%, P=0.53), BP, BMI and age did not differ between women in the highest (1513 ± 221 pg/ml) vs. lowest (279 ± 12 pg/ml) quartile of copeptin (P<0.01). In contrast, 2nd trimester CFPWV was greater (7.2 ± 0.2 vs. 6.4 ± 0.2 m/sec, P<0.05) and brachial artery FMD was lower (10.2 ± 2.8 vs. 16.5 ± 1.3 %, P<0.05) among women in the highest (1714 ± 481 pg/ml) vs. the lowest (249 ± 13 pg/ml) quartile of copeptin (P<0.01), in the absence of differences in BP, BMI or age. For the entire cohort, (log)copeptin was significantly correlated with CFPWV (r=0.23, P=0.04) and tended to correlate with FMD (r=-0.23, P=0.06) in the 2nd but not in the 1st trimester. These data suggest that elevated copeptin in mid-gestation is associated with aortic stiffness and vascular endothelial dysfunction in pregnant women at high risk for PreE, but whether increased copeptin/AVP causes vascular dysfunction in pregnancies destined for PreE requires further studies using animal models.
Author Disclosures: G.L. Pierce: None. D.A. Santillan: None. D. Fleener: None. S.M. Scroggins: None. K.K. Leslie: None. S.K. Hunter: None. J.L. Grobe: None. C.D. Sigmund: None. W.G. Haynes: None. M.K. Santillan: None.
- © 2015 by American Heart Association, Inc.