Pre-eclampsia and cardiovascular disease: metabolic syndrome of pregnancy?

doi:10.1016/j.atherosclerosis.2004.01.038

Atherosclerosis

Volume 175, Issue 2, August 2004, Pages 189-202

https://doi.org/10.1016/j.atherosclerosis.2004.01.038 Get rights and content

Abstract

Complications of pregnancy, particularly pre-eclampsia (PET) and intra-uterine growth restriction (IUGR) have been associated with future maternal cardiovascular disease (CVD). Pre-eclampsia, characterised by insulin resistance, widespread endothelial damage and dysfunction, coagulation defects and increased systemic inflammatory response, shares many risk factors with CVD. This review describes the pathology of PET and the maternal metabolic response and discusses the possible underlying mechanisms common to CVD and PET. The contributions of pre-existing risk factors and of the exaggerated atherogenic-like response seen in PET persisting post-partum to future CVD are considered. The potential for interventions based on early assessment of cardiovascular risk is addressed. We conclude that despite the low immediate cardiovascular risk in a population of young women, a pregnancy with multiple complications including PET, premature delivery and IUGR, carries a seven-fold additive risk of future disease. These women may be an appropriate cohort for CVD risk screening and for possible intervention.

Introduction

Complications of pregnancy, particularly pre-eclampsia (PET) and intrauterine growth restriction (IUGR) have been associated with future maternal cardiovascular disease (CVD). Pre-eclampsia, characterised by insulin resistance, widespread endothelial damage and dysfunction, coagulation defects and increased systemic inflammatory response, shares many risk factors with CVD. This review considers the evidence that the metabolic changes seen in normal pregnancy and the exaggerated atherogenic-like response seen in PET persist post-partum and are associated with CVD. In addition, we review the possible underlying mechanisms common to CVD and PET and the potential for interventions based on early assessment of cardiovascular risk.

Section snippets

Pregnancy and CVD risk

It is long established that female gender-specific risk factors for CVD include menopause, hysterectomy and use of exogenous hormones [1]. However, evidence is now accumulating to show that pregnancy is associated with an increase in future cardiovascular risk in women. Women, parous at index pregnancy, have a twofold higher risk of dying from ischaemic heart disease relative to primigravid women (relative risk [RR] 2.05; 95% CI 1.19–3.55; P=0.01) [2]. Women who experience an uncomplicated

General overview

In order to understand how PET might be linked to future cardiovascular risk it is important to consider its pathology. Pre-eclampsia, occurring in 2–4% of pregnancies remains one of the leading causes of maternal and neonatal morbidity and mortality in the developed world. The only definitive treatment is to deliver the baby and placenta, often prematurely in the interests of the baby or the mother. Pre-eclampsia is a multi-system disorder. The classical diagnostic criteria of hypertension

Common hypotheses underlying metabolic syndrome and PET

There are generally considered to be three main hypotheses regarding the metabolic alterations involved in the aetiology of PET, namely endothelial dysfunction and activation, insulin resistance and oxidative stress. It is unlikely that these mechanisms are independent factors in the aetiology of the disease; rather that they are all related to a certain degree, with the degree of each parameter demonstrating inter-patient variation. We will consider each hypothesis separately to demonstrate

Pre-pregnancy risk factors for PET and CVD

There is evidence to suggest that the pre-pregnancy state may be the contributing factor for the development of future CVD, rather than pregnancy or PET. Non-pregnant women may have characteristics of the metabolic syndrome such as hypertension, increased insulin resistance, obesity and lipid abnormalities which, combined with the metabolic stress of pregnancy, manifest as PET. It is possible that these pre-existing factors may present again later in life, this time as CVD, as it is well

Conclusion

Available data suggest that common genotypic and phenotypic factors may underlie both PET and coronary heart disease. However, we must interpret these data with care. Although PET is associated with a modest increase in coronary heart disease risk, the prevalence of coronary heart disease in young women is still low. On the other hand, PET may be an indicator for future risk of CVD. This association may prove to be a useful risk assessment tool, or it may be merely an epidemiological curiosity.

Acknowledgements

V. Rodie was supported by a grant from the Scottish Council for Postgraduate Medical and Dental Education for which we are very grateful.

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Chronic ingestion of excess sodium has been associated with high blood pressure, heart disease, and stroke. Limited research has suggested a relationship between increased sodium intake and the development of preeclampsia. This study investigated the association between elevated sodium in drinking water with preeclampsia using a hospital-based case-control study of 10,114 pregnant women in Iowa in the United States. Health records of women who delivered at the University of Iowa Hospitals and Clinics in Iowa City, Iowa, USA, between May 2009 and August 2020 were obtained from the Intergenerational Health Knowledgebase. Water quality data for community water systems from Safe Drinking Water Act compliance reporting and Consumer Confidence Reports (CCR) were used to estimate maternal exposure to sodium in drinking water. Logistic regression models were calculated to estimate the odds of preeclampsia based on median sodium concentrations reported by public water systems from 2000 to 2019. Preeclampsia was associated with a 38% increased odds (adjusted odds ratio (aOR) 1.38, 95% confidence interval (CI) 1.13-1.69) when women were exposed to concentrations between 20-69 milligrams per liter (mg/L), above EPA's recommendation for individuals on a very low sodium diet. Increased odds of 5% and 16% were also found at concentrations between 70-102 mg/L and greater than 256 mg/L but were not statistically significant. The lower odds at higher sodium concentrations may be due to consumers using alternative drinking water sources due to taste issues that are noted to arise between 30-60 mg/L. Preeclampsia diagnosis was strongly associated with gestational age, parity, newborn count, and body mass index. Better data on individual exposure through drinking water is needed to account for factors like home softeners, which can greatly increase sodium levels at the tap, or those users seeking out alternative water supplies (like bottled water) due to taste issues arising from greater salinity.
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HDP are strongly associated with an increased future risk of cardiovascular and metabolic disease, including a higher incidence of cardiovascular-related hospitalisations, shorter latency to CVD, and two to three times ongoing increased risk of heart disease and cerebrovascular disease compared to normotensive pregnancy controls [2,3]. Additionally, women who suffer from a hypertensive pregnancy often have features of metabolic syndrome – obesity, hypertension, insulin resistance and dyslipidaemia, further contributing factors to their cardiovascular risk profile [4]. Despite this, existing literature on the long-term cardiovascular and metabolic effects of HDP lacks data on prevention strategies, screening and treatment schedules for women with previous HDP [5].
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ReviewPre-eclampsia and cardiovascular disease: metabolic syndrome of pregnancy?

Abstract

Introduction

Section snippets

Pregnancy and CVD risk

General overview

Common hypotheses underlying metabolic syndrome and PET

Pre-pregnancy risk factors for PET and CVD

Conclusion

Acknowledgements

Lancet

Am. J. Obstet. Gynecol.

Placenta

Placenta

Am. J. Obstet. Gynecol.

Lancet

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Lancet

Clin. Chim. Acta

Lancet

Lancet

Am. J. Obstet. Gynecol.

Thromb. Res.

Am. J. Obstet. Gynecol.

Lancet

Obstet. Gynecol.

Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Atherosclerosis

Am. J. Obstet. Gynecol.

Atherosclerosis

Semin. Perinatol.

Lancet

Biochim. Biophys. Acta

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Cardiovascular sequelae of toxaemia of pregnancy

Heart

Death rates from ischemic heart disease in women with a history of hypertension in pregnancy

Acta Obstet. Gynecol. Scand.

Hypertension in pregnancy: clinical–pathological correlations and remote prognosis

Medicine (Baltimore)

Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners’ oral contraception study

Br. Med. J.

Risk factors for myocardial infarction in young women

Br. J. Prev. Soc. Med.

Fatal stroke and use of oral contraceptives: findings from a case–control study

Am. J. Epidemiol.

Rrisk of subsequent thromboembolism for patients with pre-eclampsia

Br. Med. J.

Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

Br. Med. J.

Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study

Br. Med. J.

Birth dimensions of offspring, premature birth, and the mortality of mothers

Lancet

The current impact of the hypertensive disorders of pregnancy

Clin. Exp. Hypertens.

Pregnancy outcome in 303 cases with severe preeclampsia

Obstet. Gynecol.

The prevalence of pre-eclampsia and obstetric outcome in pregnancies of normotensive and hypertensive women attending a hospital specialist clinic

Int. J. Clin. Pract.

Birth weight of offspring and mortality in the Renfrew and Paisley study: prospective observational study

Br. Med. J.

Relation between infants’ birth weight and mothers’ mortality: prospective observational study

Br. Med. J.

The anatomy of the maternal side of the placenta

J. Obstet. Gynaecol. Br. Commonw.

Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants

Br. J. Obstet. Gynaecol.

An ultrastructural study of utero-placental spiral arteries in hypertensive and normotensive pregnancy and fetal growth retardation

Br. J. Obstet. Gynaecol.

Review
Pre-eclampsia and cardiovascular disease: metabolic syndrome of pregnancy?