Objective To quantify the risk of future cardiovascular diseases, cancer, and mortality after pre-eclampsia. Design Systematic review and meta-analysis. Data sources Embase and Medline without language restrictions, including papers published between 1960 and December 2006, and hand searching of reference lists of relevant articles and reviews for additional reports. Review methods Prospective and retrospective cohort studies were included, providing a dataset of 3 488 160 women, with 198 252 affected by pre-eclampsia (exposure group) and 29 495 episodes of cardiovascular disease and cancer (study outcomes). Results After pre-eclampsia women have an increased risk of vascular disease. The relative risks (95% confidence intervals) for hypertension were 3.70 (2.70 to 5.05) after 14.1 years weighted mean follow-up, for ischaemic heart disease 2.16 (1.86 to 2.52) after 11.7 years, for stroke 1.81 (1.45 to 2.27) after 10.4 years, and for venous thromboembolism 1.79 (1.37 to 2.33) after 4.7 years. No increase in risk of any cancer was found (0.96, 0.73 to 1.27), including breast cancer (1.04, 0.78 to 1.39) 17 years after pre-eclampsia. Overall mortality after pre-eclampsia was increased: 1.49 (1.05 to 2.14) after 14.5 years. Conclusions A history of pre-eclampsia should be considered when evaluating risk of cardiovascular disease in women. This association might reflect a common cause for pre-eclampsia and cardiovascular disease, or an effect of pre-eclampsia on disease development, or both. No association was found between pre-eclampsia and future cancer.

https://www.bmj.com/content/bmj/335/7627/974.full.pdf

Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)67726-4.pdf

Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study.

Preeclampsia is a clinical syndrome defined as the new onset of hypertension and proteinuria during the second half of pregnancy1 It afflicts 3% to 5% of pregnancies and is a leading cause of maternal mortality, especially in developing countries2,3 Because the only known remedy is delivery of the placenta, in developed countries preeclampsia is an important cause of premature delivery, usually medically indicated for the benefit of the mother This results in infant morbidity and substantial healthcare expenditure4 Despite the considerable morbidity and mortality, the cause of preeclampsia has remained enigmatic

Both hypertension and proteinuria implicate the endothelium as the target of the disease The hypertension of preeclampsia is characterized by peripheral vasoconstriction and decreased arterial compliance5,6 The proteinuria of preeclampsia is associated with a pathognomonic renal lesion known as glomerular endotheliosis, in which the endothelial cells of the glomerulus swell and endothelial fenestrations are lost7,8 Podocyturia has been recently associated with preeclampsia during clinical disease9; however, whether this is the cause or effect of proteinuria is unknown The glomerular filtration rate is decreased compared with normotensive pregnant women; in rare cases, acute renal failure may develop

Preeclampsia is a systemic vascular disorder that may also affect the liver and the brain in the mothers When the liver is involved, women may present with abdominal pain, nausea, vomiting, and elevated liver enzymes Pathological examination of the liver reveals periportal and sinusoidal fibrin deposition and, in more extreme cases, hemorrhage and necrosis10 The severe preeclampsia variant HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurs in ≈20% of women with severe preeclampsia,11 and is named not only for the liver involvement, but also for the disorder of the coagulation system that develops12 Approximately 20% of …

Preeclampsia, a Disease of the Maternal Endothelium The Role of Antiangiogenic Factors and Implications for Later Cardiovascular Disease

Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses.

Plentiful evidence now links low birth weight due to intrauterine growth restriction and increased risk of vascular disease in later adult life This is considered to be partly the result of programming through fetal nutrition 1 In contrast, much less attention has been focused on the relation between adverse pregnancy outcomes, such as pre›eclampsia, gestational diabetes, preterm delivery, and intrauterine growth restriction, and the mother’s subsequent health, and interesting data are now increasingly linking the maternal vascular, metabolic, and inflammatory complications of pregnancy with an increased risk of vascular disease in later life (table) This article summarises the emerg› ing evidence to support this fascinating concept, notes important areas for further research, and discusses potential practical implications

https://www.bmj.com/content/bmj/325/7356/157.full.pdf

Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening?

ContextPreeclampsia 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.ObjectiveTo determine whether endothelial function is impaired in nonpregnant
women with previous preeclampsia and whether endothelial dysfunction is mediated
by oxidative stress.Design and SettingCase-control study conducted at 3 hospital maternity units in London,
England, between July 1997 and June 2000.ParticipantsA 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 MeasuresBrachial 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.ResultsMean (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).ConclusionsOur 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.

https://jamanetwork.com/journals/jama/articlepdf/193675/JCI10003.pdf

Michael De Swiet

Papers

Association of Maternal Endothelial Dysfunction With Preeclampsia

Association of Maternal Endothelial Dysfunction With Preeclampsia