Preeclampsia and Cerebrovascular Disease

Abstract

Preeclampsia (PE), a hypertensive disease affecting 5-8% of pregnancies, 1 is a multisystem disorder, with vascular dysfunction being central to the disease. The heterogeneity of PE's signs and symptoms has generated controversy regarding whether the cause of PE is mainly related to maternal or placental factors (Supplemental Tables S1, S2). 2 Most researchers agree that placental hypoxia and/or oxidative stress plays an important role in the pathophysiology of PE, leading to a cascade of downstream effects. 3-5 The maternal cerebral vasculature is highly vulnerable to adverse effects of PE. Short-and long-term cerebrovascular complications of PE include posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), hemorrhagic and ischemic stroke, cerebral small vessel disease, and vascular dementia. 6-10 This review summarizes current evidence and recent advances in our understanding of the effects of PE on cerebrovascular disease in women, and outlines gaps in knowledge and directions for future research. Epidemiology of preeclampsia-associated cerebrovascular disease. PE is a leading cause of maternal morbidity and mortality worldwide. 11 In African-Americans, PE has a higher prevalence and is more likely to be associated with maternal complications, including 3-fold higher mortality rates. 12,13 Cerebrovascular disease is the leading cause of maternal mortality in women with PE, with the majority of deaths due to intracerebral hemorrhage (ICH). 14-17 In the United States (US), maternal stroke accounted for 7.4 percent of maternal deaths from 2011-2014. 18 Rates of antepartum and postpartum stroke, highly associated with PE, increased 47 and 83 percent, respectively, from 1994-1995 to 2006-2007 in the US. 19 This has been directly attributed to increasing rates of PE. 19,20 PE increases the risk of maternal stroke up to 6-fold. 7,21 Risk factors for peripartum stroke in women with PE include older age, African American race, chronic preexisting hypertension, underlying prothrombotic or inflammatory disorders, and infections. 22

Signs of neuroaxonal injury in preeclampsia—A case control study

“…There is a debate about if preeclampsia contributes to later dementia, stroke and seizure disorders or if it is merely a stress test for cerebrovascular disease [ 8 ]. Thus, there is a need for an increased understanding of the direct cerebral effects of preeclampsia and there is also a need for an objective biomarker reflecting the degree of cerebral insult, preferably before complications such as eclampsia occur.…”

Selecting emergency therapy for patients with pre-eclampsia

“…Acute-onset severe hypertension (SBP/DBP ≥160/110 mmHg) measured and confirmed within 15 min during pregnancy or postpartum represents an obstetrical hypertensive emergency for both mother and fetus and requires in-hospital care and immediate BP reduction (within 30-60 min) to reduce maternal morbidity and mortality and to prolong the pregnancy for fetal benefit as much as possible [2][3][4][5][6][7][8][9]. Severe systolic, rather than diastolic, hypertension is the most important predictor of maternal acute cerebrovascular complications (stroke, intracranial hemorrhage, hypertensive encephalopathy), end organ damage and death, while DBP >110 mm Hg is associated with an increased risk of placental abruption and intrauterine growth restriction [2,5,6,10]. The goal is to reduce SBP to <160/105 mmHg over minutes to hours and then to achieve a sustained BP of 140-150/90-100 mm Hg to prevent prolonged exposure to severe systolic hypertension and the subsequent loss of cerebral vasculature autoregulation, and protect the pregnant woman from stroke and other endorgan damages, while maintaining utero-placental blood flow to avoid fetal distress [5,6,9].…”

“…The goal is to reduce SBP to <160/105 mmHg over minutes to hours and then to achieve a sustained BP of 140-150/90-100 mm Hg to prevent prolonged exposure to severe systolic hypertension and the subsequent loss of cerebral vasculature autoregulation, and protect the pregnant woman from stroke and other endorgan damages, while maintaining utero-placental blood flow to avoid fetal distress [5,6,9]. Lowering BP to 'normal' ranges (<140/90 mmHg) does not confer additional benefit but might lead to maternal end-organ hypoperfusion or affect placental perfusion and fetal growth [8][9][10]. Thus, close maternal and fetal monitoring is recommended to avoid hypotension following antihypertensive therapy.…”

Pre-eclampsia and future cardiovascular diseases: How to assess the risk?

“…Pre-eclampsia is a heterogeneous multisystem clinical syndrome defined as the new onset of hypertension in addition to signs of significant multi-organ dysfunction in a previously normotensive woman. It usually begins after 20 weeks of gestation [2]. Multiple organs can be involved including the kidneys, liver, lungs, brain, and heart.…”

“…Pre-eclampsia is a common clinical problem that affects 5 to 10% of pregnant women in the United States and up to 18% of pregnant women in some parts of Africa [4]; the prevalence is nearly 2-fold higher in first pregnancies [4]. Worldwide, 10 to 15% of direct maternal deaths are associated with pre-eclampsia/eclampsia; for the fetus, pre-eclampsia can lead to intrauterine growth restriction and oligohydramnios, as well as medically or obstetrically indicated pre-term birth [2].…”