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J O U R N A L O F T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y V O L . 7 6 , N O . 1 4 , 2 0 2 0
ª 2 0 2 0 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N
P U B L I S H E D B Y E L S E V I E R
THE PRESENT AND FUTURE
JACC STATE-OF-THE-ART REVIEW
Preeclampsia—Pathophysiology and
Clinical Presentations
JACC State-of-the-Art Review
Christopher W. Ives, MD,a Rachel Sinkey, MD,b,c Indranee Rajapreyar, MD,d Alan T.N. Tita, MD, PHD,b,c
Suzanne Oparil, MDd
ABSTRACT
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Preeclampsia is a hypertensive disorder of pregnancy. It affects 2% to 8% of pregnancies worldwide and causes sig-
nificant maternal and perinatal morbidity and mortality. Hypertension and proteinuria are the cornerstone of the disease,
though systemic organ dysfunction may ensue. The clinical syndrome begins with abnormal placentation with subsequent
release of antiangiogenic markers, mediated primarily by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin
(sEng). High levels of sFlt-1 and sEng result in endothelial dysfunction, vasoconstriction, and immune dysregulation,
which can negatively impact every maternal organ system and the fetus. This review comprehensively examines the
pathogenesis of preeclampsia with a specific focus on the mechanisms underlying the clinical features. Delivery is the
only definitive treatment. Low-dose aspirin is recommended for prophylaxis in high-risk populations. Other treatment
options are limited. Additional research is needed to clarify the pathophysiology, and thus, identify potential therapeutic
targets for improved treatment and, ultimately, outcomes of this prevalent disease.
(J Am Coll Cardiol 2020;76:1690–702) © 2020 by the American College of Cardiology Foundation.
P reeclampsia is a hypertensive disorder of
pregnancy (HDP). It impacts 2% to 8% of
all pregnancies and is a major cause of
maternal and perinatal morbidity and mortality
(1–3). In the United States, HDP were responsible
for 212 (7%) of approximately 3,000 pregnancy-
related deaths between 2011 and 2015 (4). Pre-
eclampsia is a complex disease process originating
at the maternal–fetal interface that affects
multiple organ systems (5,6). Hypertension is the
N 0735-1097/$36.00
m the aTinsley Harrison Internal Medicine Residency Program, Departmen
mingham, Alabama; bDivision of Maternal-Fetal Medicine, Department o
mingham, Birmingham, Alabama; cCenter for Women’s Reproductive H
ngham, Alabama; and the dDivision of Cardiovascular Disease, Departmen
mingham, Alabama. Dr. Sinkey has received a grant from GestVision. Dr.
m NIH/National Heart, Lung, and Blood Institute during the conduct of th
gnostics, Inc.; has received personal fees and other from CinCor Pharma In
Current Hypertension Reports (Springer Science Business Media LLC). A
ationships relevant to the contents of this paper to disclose.
e authors attest they are in compliance with human studies committe
titutions and Food and Drug Administration guidelines, including patien
it the JACC author instructions page.
nuscript received May 8, 2020; revised manuscript received July 14, 2020
cornerstone of the syndrome and is often, but not
always, accompanied by proteinuria. Severe forms
of preeclampsia can be complicated by renal, car-
diac, pulmonary, hepatic, and neurological dysfunc-
tion; hematologic disturbances; fetal growth
restriction; stillbirth; and maternal death (3,7)
(Table 1). Underlying mechanisms contributing to
the pathophysiology of preeclampsia are poorly un-
derstood, though this is an active area of interna-
tional research (5).
https://doi.org/10.1016/j.jacc.2020.08.014
t of Medicine, University of Alabama at Birmingham,
f Obstetrics & Gynecology, University of Alabama at
ealth, University of Alabama at Birmingham, Bir-
t of Medicine, University of Alabama at Birmingham,
Oparil has received grants and nonfinancial support
e study; has received personal fees from Preventric
c. outside the submitted work; and is Editor-in-Chief
ll other authors have reported that they have no
es and animal welfare regulations of the authors’
t consent where appropriate. For more information,
, accepted August 3, 2020.
https://doi.org/10.1016/j.jacc.2020.08.014
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HIGHLIGHTS
� Preeclampsia, a hypertensive disorder of
pregnancy, affects 2% to 8% of pregnant
women and causes considerable
mortality.
� Pre-existing cardiovascular disease likely
plays a role in the development of
preeclampsia.
� Delivery is the only definitive treatment.
Low-dose aspirin is recommended for
prophylaxis in high-risk women.
� Further research is needed to identify
therapies that reduce maternal and
neonatal morbidity and mortality.
AB BR E V I A T I O N S
AND ACRONYM S
Ang II = angiotensin II
AT1R = angiotensin II receptor
type 1
BP = blood pressure
HDP = hypertensive disorders
of pregnancy
IL = interleukin
RAAS = renin-angiotensin-
aldosterone system
sEng = soluble endoglin
sFlt = soluble fms-like tyrosine
kinase
Stat3 = signal transducer and
activator or transcription3
TGF = transforming growth
factor
VEGF = vascular endothelial
growth factor
J A C C V O L . 7 6 , N O . 1 4 , 2 0 2 0 Ives et al.
O C T O B E R 6 , 2 0 2 0 : 1 6 9 0 – 7 0 2 Pathophysiology of Preeclampsia
1691
PREECLAMPSIA OVERVIEW
Preeclampsia is defined as new-onset hypertension
and new-onset end-organ damage, including pro-
teinuria, after 20 weeks of gestation (Table 2) (3,7).
The pathophysiology of this complex process in-
volves multiple organ systems and is summarized in
the Central Illustration. The clinical syndrome begins
with abnormal trophoblast invasion before many
women know they are pregnant, and long before
clinical manifestations of the disease become
apparent (6,8). During normal implantation, tropho-
blasts invade the decidualized endometrium, leading
to spiral artery remodeling and obliteration of the
tunica media of myometrial spiral arteries, allowing
increased blood flow to the placenta, all independent
of maternal vasomotor changes (9). In preeclampsia,
trophoblasts fail to adopt an endothelial phenotype,
which leads to impaired trophoblast invasion and
incomplete spiral artery remodeling (6). The resultant
placental ischemia leads to an increase in angiogenic
markers such as soluble fms-like tyrosine kinase-1
(sFlt-1) and soluble endoglin (sEng) (6,10). sFlt-1 has
been proposed as an underlying mechanism to
explain disease in the maternal and fetal units. sFlt-1
binds to and decreases levels of vascular endothelial
growth factor (VEGF) and placental growth factor,
which are important mediators of endothelial cell
function, especially in fenestrated endothelium
(brain, liver, glomeruli) (6,8,10,11). Thus, endothelial
dysfunction develops in maternal vasculature (10).
sEng is a cell surface coreceptor that binds to and
decreases levels of transforming growth factor (TGF)-
b, which normally induces migration and prolifera-
tion of endothelial cells (8,11). These factors
mediate downstream effects that create endothelial
dysfunction, a vasoconstrictive state, oxida-
tive stress, and microemboli that contribute
to the involvement of multiple organ sys-
tems, and thus, the clinical features of pre-
eclampsia (8,9,12). It is also likely that pre-
existing endothelial stress, such as
increased sympathetic nervous system tone
from reduced intravascular volume, may
further predispose to development of pre-
eclampsia (2).
In addition to endothelial dysfunction,
immunologic aberrations contribute to the
preeclampsia phenotype. In normal preg-
nancy,2018;132:e44–52.
76. LeFevre ML, U.S. Preventive Services Task
Force. Low-dose aspirin use for the prevention
of morbidity and mortality from preeclampsia: U.
S. Preventive Services Task Force recommenda-
tion statement. Ann Intern Med 2014;161:
819–26.
77. Duley L, Meher S, Hunter KE, Seidler AL,
Askie LM. Antiplatelet agents for preventing pre-
eclampsia and its complications. Cochrane Data-
base Syst Rev 2019;2019:CD004659.
78. Barakat R, Pelaez M, Cordero Y, et al. Exercise
during pregnancy protects against hypertension
and macrosomia: randomized clinical trial. Am J
Obstet Gynecol 2016;214:649.e1–8.
79. Syngelaki A, Sequeira Campos M, Roberge S,
Andrade W, Nicolaides KH. Diet and exercise for
preeclampsia prevention in overweight and obese
pregnant women: systematic review and meta-
analysis. J Matern Fetal Neonatal Med 2019;32:
3495–501.
80. Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L,
Torloni MR. Calcium supplementation during
pregnancy for preventing hypertensive disorders
and related problems. Cochrane Database Syst
Rev 2014;6:CD001059.
81. Hofmeyr GJ, Lawrie TA, Atallah AN,
Torloni MR. Calcium supplementation during
pregnancy for preventing hypertensive disorders
and related problems. Cochrane Database Syst
Rev 2018;10:CD001059.
82. Fox KA, Longo M, Tamayo E, et al. Effects of
pravastatin on mediators of vascular function in a
mouse model of soluble Fms-like tyrosine kinase-
1-induced preeclampsia. Am J Obstet Gynecol
2011;205:366.e1–5.
83. Kraker K, O’Driscoll JM, Schutte T, et al. Sta-
tins reverse postpartum cardiovascular dysfunc-
tion in a rat model of preeclampsia. Hypertension
2020;75:202–10.
84. Costantine MM, Cleary K, Hebert MF, et al.
Safety and pharmacokinetics of pravastatin used
for the prevention of preeclampsia in high-risk
pregnant women: a pilot randomized controlled
trial. Am J Obstet Gynecol 2016;214:720.e1–17.
85. Costantine MM, Cleary K. Eunice Kennedy
Shriver National Institute of Child Health and Hu-
man Development Obstetric–Fetal Pharmacology
Research Units Network. Pravastatin for the pre-
vention of preeclampsia in high-risk pregnant
women. Obstet Gynecol 2013;121 Pt 1:349–53.
86. Syngelaki A, Nicolaides KH, Balani J, et al.
Metformin versus placebo in obese pregnant
women without diabetes mellitus. N Engl J Med
2016;374:434–43.
87. Thilaganathan B, Kalafat E. Cardiovascular
system in preeclampsia and beyond. Hypertension
2019;73:522–31.
88. Mehta LS, Warnes CA, Bradley E, et al. Car-
diovascular considerations in caring for pregnant
patients: a scientific statement from the American
Heart Association. Circulation 2020;141:
e884–903.
KEY WORDS hypertension, hypertensive
disorders of pregnancy, maternal morbidity,
pathogenesis, pregnancy
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	Preeclampsia—Pathophysiology and Clinical Presentations
	Preeclampsia Overview
	Hypertension
	Proteinuria
	Renal Dysfunction
	Neurological Dysfunction
	Eclampsia
	Cardiac Dysfunction
	Pulmonary Edema
	Hepatic Dysfunction
	Hematologic Disturbance
	Fetal growth Restriction/Fetal Implications
	Prevention
	Conclusions
	Acknowledgment
	ReferencesT helper cells shift toward the anti-
inflammatory Th2 phenotype, which helps
to neutralize proinflammatory cytokines,
angiotensin II type 1 receptor (AT1R) auto-
antibodies, placental reactive oxygen species,
and endothelin-1 (2). However, in pre-
eclampsia, T helper cells shift toward the Th1
phenotype, increasing release of proinflammatory
cytokines such as interleukin (IL)-12 and IL-18, and
decreasing IL-10, which leads to apoptosis and
reduced trophoblast invasion (13). Increased
CD19þCD5þ B lymphocytes may contribute to pro-
duction of antiangiogenic factors. Uterine natural
killer cells, which differ from peripheral natural killer
cells, are likely involved, because inhibition of uter-
ine natural killer cells may lead to defective spiral
artery remodeling. Syncytial knots, vesicles that shed
from trophoblasts, may stimulate an inflammatory
response in the placenta (2). LIN28 is an RNA binding
protein that affects cell metabolism, differentiation,
growth, and invasion. Two paralogs exist: LIN28A and
LIN28B. LIN28B is increased in extravillous tropho-
blasts/placenta in normal pregnancy. In preeclamp-
sia, levels are decreased in the placenta, suggesting a
role in preeclampsia by reducing trophoblast differ-
entiation and invasion, and by promoting inflamma-
tion (14). Elevated complement levels in
preeclampsia result in complement system dysregu-
lation and additional increases in sFlt-1 (2). Women
with preeclampsia have reduced histocompatibility
complex human leukocyte antigen-G and -E, also
suggestive of immune imbalance (13).
Multiple genetic components have been implicated
in the pathogenesis of preeclampsia. Mutations in
complement component 3 are associated with pre-
eclampsia, which may partly account for complement
system dysregulation (2). Corin, a cardiac protein that
activates atrial natriuretic peptide, has also been
localized to uterine tissue, and mutations in corin
associated with preeclampsia have been identified
(2,15). Global transcriptional profiling of chorionic
TABLE 1 Highlights of Clinical Features of Preeclampsia
Clinical Feature Underlying Abnormalities Clinical Consequences
Hypertension Increased SVR and afterload
Decreased CO and intravascular volumes
Activation of RAAS, ET-1, SNS
AT1R down-regulated, placental hypoxia, and AT1R autoantibodies
Increased vasoconstrictors, decreased vasodilators
Increased sFlt-1 and sEng, oxidative stress
Heart failure
Pulmonary edema
Renal dysfunction
Neurological injury
Proteinuria Glomerular endotheliosis
Disruption of filtration barrier
Increased tubular permeability
Hypertension
Ischemic heart disease
Stroke
Chronic kidney disease
End-stage renal disease
Renal dysfunction Decreased RBF and GFR
Glomerular endotheliosis
Increased tissue factor expression
Thrombotic microangiopathy
Hypertension
Chronic kidney disease
End-stage renal disease
Neurological abnormalities Headache: loss of fenestrae on choroid plexus, periventricular edema,
vasogenic edema in posterior cerebral circulation
Visual disturbances: retinopathy, retinal detachment, cortical blindness,
central serous chorioretinopathy, hypertensive retinopathy, diabetic
retinopathy
Seizures
PRES
Permanent blindness
Eclampsia Unknown (potentially vasogenic or cytotoxic edema) Permanent neurological dysfunction
Cardiac dysfunction Increased SVR, afterload
Concentric LV hypertrophy, LA enlargement
Increased RVSP, increased LV filling pressures, LV diastolic dysfunction,
Heart failure
Peripartum cardiomyopathy
Pulmonary edema Increased vascular permeability
Cardiac dysfunction
Corticosteroids/tocolytics
Iatrogenic volume overload
Acute hypoxemic respiratory failure
Hepatic dysfunction Hepatic microcirculatory deterioration, hepatocellular injury Liver failure, hepatic rupture
Hematologic dysfunction Procoagulant state Thrombocytopenia, DIC
Fetal growth restriction Incomplete spiral artery remodeling
Decidual vasculopathy
Uterine and placental dysfunction
Fetal growth 30) and diabetes each carries a relative
risk increase of 3.5 (2). Chronic hypertension, chronic
kidney disease, obstructive sleep apnea, pre-
gestational diabetes, systemic lupus erythematosus,
antiphospholipid syndrome, rheumatoid arthritis,
maternal age over 35 years, nulliparity, multifetal
gestations, fetal hydrops, hydatidiform moles, and
assisted reproductive technologies are also associated
with preeclampsia (2,3,13,21–23). Though abnormal
placentation may drive the more immediate devel-
opment of preeclampsia, the preceding information
suggests an underlying role of pre-existing cardio-
vascular and other organ dysfunction before
TABLE 2 Diagnostic Criteria for Preeclampsia
Always necessary. . .
Hypertension
� SBP $140 mm Hg or DBP $90 mm Hg on 2 occasions at least 4 h apart after 20 weeks’ gestation in a woman with previously normal BP
� SBP $160 mm Hg or DBP $110 mm Hg on 1 occasion
. . .And 1 of the following
Proteinuria
� $300 mg per 24-h urine collection (or extrapolated from timed collection), or
� Protein/creatinine ratio of $0.3 mg/dl, or
� Dipstick reading of 2þ (used only when other methods not available)
OR any 1 of the following (in the absence of proteinuria)
Thrombocytopenia
� Platelet count 1.1 mg/dl or a doubling of serum creatinine concentration in the absence of other renal disease
Impaired liver function
� Elevated concentration of liver transaminases to 2� normal
� Severe persistent right upper quadrant or epigastric pain unresponsive to medication
Pulmonary edema
� Diagnosed by physical examination or chest x-ray
Neurological signs
� New-onset headache unresponsive to medication and not accounted for byalternative diagnoses or visual symptoms
� Visual disturbances
Fetal growth restriction*
� Estimated fetal weight 1.1 mg/dl or a doubling of baseline
creatinine (38). Renal blood flow and glomerular
filtration rate are often decreased in preeclampsia
(11). Biopsy changes in these patients include diffuse
fibrin deposition, endothelial swelling, loss of podo-
cytes, and loss of capillary space (glomerular endo-
theliosis) (6,8). Dysregulation of the glomerular
filtration apparatus occurs in the setting of glomer-
ular endotheliosis (6). In normal pregnancy,
increased tissue factor release from the maternaldecidua and placenta shifts endothelial cells to a
procoagulant balance (36). Increased proin-
flammatory cytokines in preeclampsia further stimu-
late tissue factor expression by endothelial cells and
leukocytes (8,39). Damaged endothelial cells then
further induce clotting and lose anticoagulant ability
as prostaglandin and nitric oxide levels decrease,
leading to thrombotic microangiopathy in the kidneys
(36). Increased toll-like receptor 4 leads to increased
inflammatory cytokines, which in turn increase both
placental and renal dysfunction (10). Electrolyte ab-
normalities occur as urinary calcium decreases due to
increased tubular calcium reabsorption (3). Reduction
in intravascular volumes in preeclampsia increases
sodium and free-water retention (3). Lastly, the same
mechanisms that trigger hypertension, particularly
involving sFlt-1 and the RAAS system, predispose to
renal dysfunction and acute kidney injury, which in-
crease later risk of hypertension, chronic kidney dis-
ease, and end-stage renal disease (8,29,31).
NEUROLOGICAL DYSFUNCTION
Preeclampsia may lead to multiple neurological
problems, including headache, visual disturbances,
seizure, posterior reversible encephalopathy syn-
drome, and hemorrhagic stroke (35,38). Multiple
variants of primary headache including tension type
headache, migraine without aura, and migraine with
aura are associated with preeclampsia (40). Second-
ary headache accounts for 35% of headache in preg-
nancy. HDPs, most commonly preeclampsia, are the
most frequent cause of secondary headache and
become more common as gestational age increases
(40,41). Use of nifedipine for severe hypertension and
intravenous magnesium sulfate for eclampsia pro-
phylaxis may also cause headache (41). The charac-
teristic preeclampsia headache is progressive,
bilateral (frontal or occipital), pulsating/throbbing,
associated with visual changes, worse with higher BP,
aggravated by physical activity, and unresponsive to
over-the-counter medications (40,41). Symptoms can
also be vague and typical of tension-type headache
(41). The characteristic posterior reversible encepha-
lopathy syndrome headache is bilateral, occipital,
dull, and with no prodrome (40). One theory of the
pathophysiology of headache in preeclampsia is that
blocking VEGF and TGF-b leads to loss of fenestrae on
the choroid plexus, resulting in endothelial cell
instability and periventricular edema (5). These
changes may then precipitate seizures and posterior
reversible encephalopathy syndrome, defined by
neurological abnormalities with neuroimaging find-
ings of vasogenic edema in the distribution of the
posterior cerebral circulation (5,42).
Visual disturbance in preeclampsia may be due to
retinopathy, retinal detachment, or cortical blind-
ness, which typically resolves following delivery
(35,43). Central serous chorioretinopathy occurs as
fluid accumulates behind the retina, leading to
detachment (44). It is thought to arise from hormonal
fluctuations, such as progesterone level changes (45).
Hypertensive retinopathy is a condition of retinal
microvascular damage secondary to elevated blood
pressure (46). It results from severe vascular spasm in
the setting of the angiogenic imbalance of pre-
eclampsia (45,46). In central serous chorioretinop-
athy and hypertensive retinopathy, delivery results
in spontaneous resolution of subretinal fluid, with
generally good outcomes, so these conditions are not
emergent indications for delivery (45). By contrast,
diabetic retinopathy can progress quickly in preg-
nancy and up to 1 year postpartum, so close moni-
toring and treatment with laser photocoagulation
after progression to severe pre-proliferative diabetic
retinopathy is recommended (44,45). However,
regression to a prior state of retinopathy can occur in
the postpartum period (44). Retinal artery occlusion
can also occur and is associated with Protein S defi-
ciency, elevated factor VIII, and primary anti-
phospholipid antibody syndrome (45). Cortical
blindness is vision loss due to lesions of the occipital
cortex, possibly due to cerebral edema. It generally
Ives et al. J A C C V O L . 7 6 , N O . 1 4 , 2 0 2 0
Pathophysiology of Preeclampsia O C T O B E R 6 , 2 0 2 0 : 1 6 9 0 – 7 0 2
1696
resolves in hours to days (44). Though some visual
disturbances are temporary, others can result in per-
manent visual disturbance or blindness despite
prompt clinical recognition and management.
ECLAMPSIA
Eclampsia is defined as new-onset tonic-clonic, focal,
or multifocal seizures in the setting of HDP in the
absence of other causes (3). Although progesterone
raises the seizure threshold, estrogen lowers the
seizure threshold via down-regulation of gamma
aminobutyric acid (8). A Cochrane review of medica-
tions for preeclampsia found that intravenous mag-
nesium sulfate reduced the risk of eclampsia by 59%,
superior to phenytoin (47). It is unknown why mag-
nesium sulfate works or why it is more effective than
other medications, though it appears to be through
mechanisms other than anticonvulsant properties.
The mechanism may be related to mitigating the
endothelial injury underlying preeclampsia (48).
Patients with eclampsia who undergo magnetic
resonance imaging typically have findings suggestive
of posterior reversible encephalopathy syndrome.
However, these findings were seen in areas of the
brain other than the posterior cerebrum (42).
Eclampsia can develop with systolic BPsystolic pressures, increased left
atrial size, increased left ventricular wall thickness,
diastolic dysfunction, and increased left ventricular
filling pressures. Another study (51) used cardiovas-
cular magnetic resonance imaging and found that
postpartum women with preeclampsia had left atrial
enlargement compared with the control group of
postpartum women without preeclampsia. HDP in-
crease the risk of peripartum cardiomyopathy, a
serious complication of pregnancy (52,53). Peri-
partum cardiomyopathy is defined as reduced left
ventricular ejection fraction (inflammatory response (8). It is important to monitor
women with preeclampsia for hematologic abnor-
malities to support them through this potentially
deadly feature of preeclampsia.
FETAL GROWTH RESTRICTION/
FETAL IMPLICATIONS
Preeclampsia leads to uterine and placental
dysfunction, which causes fetal growth restriction,
defined as an estimated fetal weightclin-
ical features of preeclampsia, particularly super-
imposed eclampsia, hepatic dysfunction, hematologic
disturbances, and cardiac remodeling and dysfunc-
tion. Nonetheless, the clinical relevance of this dis-
ease process is well-documented, given the
substantial effect on maternal and perinatal
morbidity and mortality, in both the short and
long term. Many ongoing research activities are
actively seeking to better understand this common
disorder that impacts 2% to 8% of pregnancies.
Opportunities for future research include defining
the roles of pre-existing diseases in the pathogenesis
of preeclampsia, elucidating immunologic predis-
positions and genetic etiologies (such as LIN28B), and
further refining the link between preeclampsia
and short- and long-term cardiovascular diseases.
Meanwhile, prompt diagnosis, close observation, and
delivery when indicated are the mainstays of treat-
ment to reduce maternal and fetal morbidity and
mortality.
ACKNOWLEDGMENT The authors thank Mikako
Kawai, who assisted with the Central Illustration and
Figure 1 design.
ADDRESS FOR CORRESPONDENCE: Dr. Christopher
W. Ives, Tinsley Harrison Internal Medicine Resi-
dency Program, Department of Medicine, University
of Alabama at Birmingham, 1720 2nd Avenue
South, ZRB 1034, Birmingham, Alabama 35294-0007.
E-mail: cives@uabmc.edu. Twitter: @UABCardiology,
@UAB_CWRH, @uabmedicine.
https://www.clinicaltrials.gov/ct2/show/NCT01717586
mailto:cives@uabmc.edu
https://twitter.com/UABCardiology
https://twitter.com/UAB_CWRH
https://twitter.com/uabmedicine
J A C C V O L . 7 6 , N O . 1 4 , 2 0 2 0 Ives et al.
O C T O B E R 6 , 2 0 2 0 : 1 6 9 0 – 7 0 2 Pathophysiology of Preeclampsia
1701
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