Association of Maternal Endothelial Dysfunction With Preeclampsia

Abstract

CONTEXT: Preeclampsia is believed to result from release of placental factors that damage maternal vascular endothelium. However, because most studies have been conducted during pregnancy, it has not been possible to separate maternal from placental mechanisms underlying endothelial dysfunction in preeclampsia. OBJECTIVE: To determine whether endothelial function is impaired in nonpregnant women with previous preeclampsia and whether endothelial dysfunction is mediated by oxidative stress. DESIGN AND SETTING: Case-control study conducted at 3 hospital maternity units in London, England, between July 1997 and June 2000. PARTICIPANTS: A total of 113 women with previous preeclampsia (n = 35 with recurrent episodes; n = 78 with a single episode) and 48 women with previous uncomplicated pregnancies, all of whom were at least 3 months (median, 3 years) postpartum. MAIN OUTCOME MEASURES: Brachial artery flow-mediated (endothelium-dependent) and glyceryl trinitrate-induced (endothelium-independent) dilatation were compared between previously preeclamptic women and controls. To investigate oxidative stress, these measurements were repeated after administration of ascorbic acid, 1 g intravenously, in 15 cases and 15 controls. RESULTS: Mean (SD) flow-mediated dilatation was lower in women with previous preeclampsia compared with controls (recurrent group, 0.9% [4.1%]; single-episode group, 2.7% [3.5%]; and control group, 4.7% [4.3%]; P<.001). In contrast, glyceryl trinitrate-induced dilatation was similar in the 3 groups (recurrent, 19.5% [5.9%]; single-episode, 21.0% [8.0%]; and control, 21.0% [8.3%]; P =.65). Impaired flow-mediated dilatation in previously preeclamptic women was not accounted for by recognized vascular risk factors. Ascorbic acid administration increased flow-mediated dilatation in previously preeclamptic women (baseline, 2.6% [3.3%]; after administration, 5.6% [3.0%]; P =.001) but not in controls (baseline, 6.2% [3.3%]; after administration, 6.7% [5.0%]; P =.72). CONCLUSIONS: Our results indicate that endothelial function is impaired in women with previous preeclampsia and is not explained by established maternal risk factors but is reversed by antioxidant ascorbic acid administration.