Low Plasma Volume in Normotensive Formerly Preeclamptic Women Predisposes to Hypertension

Abstract

P reeclampsia is a serious hypertensive pregnancy disorder complicating 2% to 5% of all pregnancies. Preeclampsia is characterized by hypertension and proteinuria after 20 weeks of gestation. Women with a history of preeclampsia are at increased risk to develop early onset cardiovascular disease (CVD) later in life when compared with women who had an uneventful pregnancy.1 Therefore, in 2011, the American Heart Association added preeclampsia to the list of risk factors for developing CVD.2 The mechanistic explanation for the link between preeclampsia and later CVD remains to be elucidated. 3Numerous studies demonstrated increased prevalence of cardiovascular risk factors after a pregnancy complicated by preeclampsia. [4][5][6] Most formerly preeclampsia women, however, do not demonstrate a traditional cardiovascular risk profile within the first years after preeclampsia.6 Yet, when compared with healthy parous controls, the relative risk of developing chronic hypertension within 15 years after preeclampsia is estimated 3.7 (95% confidence interval, 2.7-5.5).1 This observation indicates that a subset of normotensive formerly preeclampsia women is at risk to develop hypertension within the first years after the affected pregnancy. It is conceivable that these formerly preeclampsia women have subtle or latent abnormalities that could explain the increased cardiovascular risk after pregnancy.Low plasma volume (PV) is considered to reflect latent hypertension, 7 and normotensive formerly preeclampsia women with low PV (LPV) are prone to develop recurrent hypertensive disease in subsequent pregnancy. 8 Whether PV status also relates to chronic hypertension after a pregnancy complicated by preeclampsia has never been studied before. We hypothesized that LPV status in normotensive formerly preeclampsia women predisposes to the development of hypertension. In this longitudinal study, we additionally studied how the traditional cardiovascular and metabolic risk profiles evolve over time after a preeclamptic pregnancy.Abstract-Formerly preeclamptic women are at risk for cardiovascular disease. Low plasma volume may reflect latent hypertension and potentially links preeclampsia with chronic cardiovascular disease. We hypothesized that low plasma volume in normotensive formerly preeclamptic women predisposes to hypertension. We longitudinally studied n=104 formerly preeclamptic women in whom plasma volume was measured 3 to 30 months after the preeclamptic pregnancy. Cardiovascular variables were assessed at 2 points in time (3-30 months postpartum and 2-5 years thereafter). Study population was divided into low plasma volume (≤1373 mL/m 2 ) and normal plasma volume (>1373 mL/m 2 ). Primary end point was hypertension at the second visit: defined as ≥140 mm Hg systolic or ≥90 mm Hg diastolic. Secondary outcome of this study was change in traditional cardiovascular risk profile between visits. Variables correlating univariately with change in blood pressure between visits were introduced in regression analysis. Eighteen of 104 ...

Recurrence of pre‐eclampsia and the risk of future hypertension and cardiovascular disease: a systematic review and meta‐analysis

“…Five studies found higher risk of antihypertensive medication use when pre‐eclampsia was recurrent compared with a single complicated pregnancy and when compared with women with uncomplicated pregnancy only . Two smaller studies looked at the proportion of recurrent pre‐eclampsia in women who were hypertensive at follow up after having had pre‐eclampsia in the index pregnancy and found conflicting results . Three studies observed women who went on to have subsequent pregnancies after pre‐eclampsia, in the first two articles a nonsignificant association was mentioned in the text .…”

“…Several studies within this review discussed timing as a factor in determining cardiovascular risk, morbidity and mortality. When looking at cardiovascular risk markers, studies found significant correlation after many years of follow up, even though these markers may not be apparent soon after pregnancy . A few studies analysed time between pre‐eclampsia and CVD in their set‐up, reporting a significantly shorter time to cardiovascular events in the recurrent group with a significantly accelerated disease progression.…”

Plasma volume variation across the menstrual cycle among healthy women of reproductive age: A prospective cohort study

“…Plasma volume showed a strong positive correlation with body weight, lean body mass, and body surface area, but no correlations with plasma osmolality, blood pressure (systolic and diastolic blood pressure), or reproductive hormones (estradiol or progesterone). Though plasma volume measures often focus on changes during pregnancy, recent studies have shown that prepregnant plasma volume could be an important factor in predicting risk of recurrent preeclampsia, recurrent pregnancy loss, and risk of preterm delivery (Donckers et al, 2012; Scholten et al, 2011; Aardenburg et al, 2003, 2006; Donckers et al, 2012; Scholten et al, 2011, 2015; Spaanderman et al, 2001; Stekkinger et al, 2015).…”

“…Increasing levels of estrogen and progesterone, as well as changes in the renin‐angiotensin‐aldosterone system (RAAS), play a role in the increase in plasma volume across gestation. Compared with normal plasma volume, women with low plasma volume are at an increased risk of gestational hypertension, recurrent preeclampsia, recurrent pregnancy loss, and preterm delivery (Aardenburg, Spaanderman, Eijndhoven, Leeuw, & Peeters, 2006; Aardenburg et al, 2003; Donckers et al, 2012; Scholten et al, 2011, 2015; Spaanderman et al, 2001; Stekkinger, Scholten, Heidema, & Spaanderman, 2015). While plasma volume expansion in pregnancy has long been established, our knowledge of plasma volume across the menstrual cycle is limited.…”

Plasma volume expansion across healthy pregnancy: a systematic review and meta-analysis of longitudinal studies

“…Since that time, there have been additional studies of plasma volume, but not many. Adverse pregnancy outcomes, including hypertensive disorders of pregnancy, have been linked to reduced plasma volume expansion during pregnancy [4][5][6][7]. Plasma volume in the third trimester [8][9][10] and total plasma volume expansion [10][11][12][13] are both positively associated with birthweight.…”