Impaired Flow-Mediated Dilation Before, During, and After Preeclampsia

Abstract

Endothelial dysfunction is believed to play a critical role in preeclampsia, however it is unclear whether this dysfunction precedes the pregnancy or is caused by early pathophysiological events. It is also unclear for how long vascular dysfunction may persist post-partum, and whether it represents a mechanism linking preeclampsia with future cardiovascular disease. Our objective was to determine whether women with preeclampsia have worse vascular function compared to women who did not have preeclampsia by performing systematic review and meta-analysis of studies that examined endothelial dysfunction using flow-mediated dilation (FMD). We included studies published before May 29, 2015 that examined FMD before, during and after preeclampsia. Differences in FMD between study groups were evaluated by standardized mean differences. Out of 610 abstracts identified through PubMED, EMBASE and Web of Science, 37 studies were eligible for the meta-analysis. When compared to women who did not have preeclampsia, women who had preeclampsia had lower FMD prior to the development of preeclampsia (~20–29 weeks gestation), at the time of preeclampsia, and for three years post-partum, with the estimated magnitude of the effect ranging between 0.5 and 3 standard deviations. Similar effects were observed when the analysis was limited to studies that excluded women with chronic hypertension, smokers, or both. Vascular dysfunction predates preeclampsia and may contribute to its pathogenesis. Future studies should address whether vascular changes that persist after preeclamptic pregnancies may represent a mechanistic link with the increased risk for future cardiovascular disease.

Maternal Vascular Physiology in Preeclampsia

“…4 Components of aberrant vascular physiology in preeclampsia include impaired vascular endothelial function, 5 incomplete uterine artery remodeling, 6,7 augmented vasoconstriction, 8,9 vascular oxidative stress, and inflammation 10,11 Studies using flow-mediated dilation have shown that women who had preeclampsia had lower flow-mediated dilation before clinical diagnosis of preeclampsia, at the time of preeclampsia, and for 3 years postpartum, suggesting that vascular dysfunction may play a role in the pathogenesis of preeclampsia and may be a link between preeclampsia and high risk for cardiovascular disease later in life. 12 The main objective of this brief review is to discuss the molecular mechanisms underlying aberrant maternal vascular physiology in reproductive and nonreproductive vascular beds in preeclampsia. Evidence from studies in experimental animals and in humans will be discussed.…”

Systemic Evaluation of Vascular Dysfunction by High‐Resolution Sonography in an Nω‐Nitro‐l‐Arginine Methyl Ester Hydrochloride–Induced Mouse Model of Preeclampsia‐Like Symptoms

“…Patients with preeclampsia had reduced flow-mediated dilatation before the development of preeclampsia, at the time of preeclampsia, and for 3 years postpartum, even excluding women with chronic hypertension, smokers, or both. 30 We present the fundamental physiologic mechanism of flowmediated dilatation in the hind limb of mice, which is analogous to human flow-mediated dilatation measurements. We found that transient hind limb ischemia (5 minutes) led to reactive hyperemia with flow velocity and wall shear stress increases and was followed by femoral artery dilatation.…”

“…Healthy arteries dilate via the release of nitric oxide or other endothelium‐derived vasoactive substances. Patients with preeclampsia had reduced flow‐mediated dilatation before the development of preeclampsia, at the time of preeclampsia, and for 3 years postpartum, even excluding women with chronic hypertension, smokers, or both . We present the fundamental physiologic mechanism of flow‐mediated dilatation in the hind limb of mice, which is analogous to human flow‐mediated dilatation measurements.…”

“…However, the latter was partly abolished by administration of l ‐NAME for 10 days. Endothelial dysfunction potentially plays a critical role in preeclampsia . Flow‐mediated dilatation at 120 seconds was an independent diagnostic criterion for the l ‐NAME‐treated preeclampsia model.…”

First and second trimester maternal serum inhibin A levels in twins with pre-eclampsia

“…Although the pathophysiology of PE remains elusive, there is general agreement that the trophoblast layer in the placenta is involved . This explains why early in singleton pregnancies the concentrations of several maternal serum analytes for those which later present with PE differ from unaffected singletons .…”