Hemodynamically-directed atenolol therapy is associated with a blunted rise in maternal sFLT-1 levels during pregnancy.
OBJECTIVE
Cardiac output and sFlt-1 are elevated prior to clinical evidence of preeclampsia. Early treatment of high cardiac output with atenolol decreases the risk for preeclampsia. We hypothesized that atenolol would impact circulating sFlt-1.


METHODS
Cardiac output and plasma sFlt-1 were measured <or=24 weeks' gestation and every 6 to 8 weeks in a longitudinal pilot study of: 1) women with risk factors for preeclampsia (high-risk group; n=46) who were treated with atenolol, and 2) low-risk group (control, n=25) who were not treated.


RESULTS
The groups were similar in maternal age (mean+/-SD: high-risk 28.3+/-5.4 versus control 30.3+/-5.5 years) and enrollment gestational age (17.3+/-4.3 versus 16.1+/-4.2 weeks). The high-risk group had higher cardiac output (9.7+/-1.7 versus 7.3+/-1.7 L/min; p<0.001) and mean arterial pressure (91.8+/-10.6 versus 79.6+/-7.3 mm Hg; p<0.001). Cardiac output and mean arterial pressure decreased while sFlt-1 levels rose less in the high-risk group compared with controls (p=0.001 for all using GEE) even after adjusting for preeclampsia risk factors (age, weight, and primigravida status).


CONCLUSIONS
Atenolol in high-risk women was associated with a lower rise in sFlt-1, suggesting an effect of hemodynamically directed treatment on the anti-angiogenic state.
Carr
Darcy B
DB
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington 98195-6460, USA. darcarr@u.washington.edu
Tran
Lan T
LT
Brateng
Debra A
DA
Kawamura
Cydney
C
Shofer
Jane B
JB
Karumanchi
S Ananth
SA
Easterling
Thomas R
TR
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use*; D016534:Cardiac Output, High / Q000188:drug therapy; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008137:Longitudinal Studies; D010865:Pilot Projects; D011225:Pre-Eclampsia / Q000517:prevention & control*; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
D000959:Antihypertensive Agents; D001262:Atenolol; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1