Original Research ajog.

org

OBSTETRICS
Effect of early-onset preeclampsia on cardiovascular risk in
the fifth decade of life
Anouk Bokslag, MD; Pim W. Teunissen, MD, PhD; Constantijn Franssen, MD, PhD; Floortje van Kesteren, MD;
Otto Kamp, MD, PhD; Dr. Wessel Ganzevoort, MD, PhD; Walter J. Paulus, MD, PhD; Christianne J. M. de Groot, MD, PhD

BACKGROUND: Women with hypertensive disorders in pregnancy, in
particular early-onset preeclampsia, are at increased risk of developing
cardiovascular disease later in life. These women have a more than 2-fold
increased risk of dying from cardiovascular diseases. Most studies have
focused on identification of risk factors shortly after pregnancy. Less is
known on the prevalence of risk factors or actual signs of cardiovascular
disease 5e20 years later. The presence of hypertension or metabolic
syndrome can be seen as an opportunity for preventive interventions to
reduce the development of severe cardiovascular diseases like myocardial
infarction and stroke.
OBJECTIVE: To assess cardiovascular risk factors and established
cardiovascular disease in women after early-onset preeclampsia, in the
fifth decade of life. As a consequence, we can assess whether there is
still a window of opportunity for preventive measures and to establish
in what proportion of women cardiovascular disease already has
developed.
STUDY DESIGN: In a prospective observational study, cardiovascular
risk assessment was performed in women with early-onset preeclampsia
(<34 weeks gestation) and normotensive controls (
37 weeks gesta-
tion) 916 years after their index pregnancy. Medical records of 2 tertiary
hospitals in Amsterdam, The Netherlands, were screened consecutively,
and all eligible women were invited. Cardiovascular risk assessment
consisted of a questionnaire, blood pressure measurement, anthropo-
metrics, and blood and urine for fasting lipids, lipoproteins, glucose levels,
glycated hemoglobin, renal function, N-terminal brain natriuretic peptide,
and albuminuria. History of cardiovascular diseases (ie, myocardial
infarction and stroke) was determined. Prevalence of women presenting in
an optimal window of opportunity for preventive measures was defined by
the presence of cardiovascular risk factors (ie, hypertension and metabolic
syndrome) but in the absence of established cardiovascular diseases (ie,
myocardial infarction and stroke).
RESULTS: Women with a history of early-onset preeclampsia (n 131)
had significantly greater systolic and diastolic blood pressure, greater body
mass index, more often had an abnormal lipid profile (lower high-density
lipoprotein levels, higher triglycerides), greater glycated hemoglobin, and
greater levels of albuminuria compared to controls (n 56). None of the
women with a history of early-onset preeclampsia was diagnosed with
cardiovascular disease; 38.2% were diagnosed with hypertension; and
18.2% were diagnosed with metabolic syndrome. A total of 42% met the
criteria for the window of opportunity for preventive measures. In women
with a history of an uncomplicated pregnancy, no women were diagnosed
with cardiovascular disease; 14.3% were diagnosed with hypertension;
1.8% with metabolic syndrome. In this cohort, 14.3% met the criteria for
the window of opportunity for preventive measures.
CONCLUSION: A large proportion of women who experienced early-
onset preeclampsia had major cardiovascular risk factors in the fifth
decade of life, compared with healthy controls. These women are currently
outside the scope of most preventive programs due to their relatively young
age, but have important modifiable risk factors for cardiovascular
diseases.
Key words: cardiovascular disease, cardiovascular risk factors, early-
onset preeclampsia, metabolic syndrome, preeclampsia, prevention,
womens health

P reeclampsia is a pregnancy-specic
disorder that affects 35% of all
pregnancies and is a leading cause of
maternal and neonatal morbidity
and mortality.1 The disorder is charac-
terized by hypertension with 1 or more
of the following new-onset conditions:
new-onset proteinuria, thrombocyto-
penia, impaired liver function, new-
onset renal insufciency, pulmonary
Cite this article as: Bokslag A, Teunissen PW, Franssen C,
et al. Effect of early-onset preeclampsia on cardiovascular
risk in the fifth decade of life. Am J Obstet Gynecol
2017;:.
0002-9378/$36.00
2017 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2017.02.015
edema, or new-onset cerebral or visual
disturbances.2
The association between preeclampsia
and cardiovascular disease later in life is
well established.3,4 Cardiovascular dis-
ease is the leading cause of death in
women in the Western world.5 Women
with a history of preeclampsia even have
a more than 2-fold increased risk of
dying from cardiovascular diseases.4 It is
not clear whether the relationship be-
tween preeclampsia and cardiovascular
disease is causative or that preeclampsia
is an early manifestation (ie, a stress test)
of cardiovascular disease, because the
pathophysiological link has not been
elucidated fully. Nonetheless, the occur-
rence in relatively young women creates
an opportunity for early identication of
women at risk and, if necessary, pre-
ventive measures and interventions can
be undertaken early in life.6
The inuence of cardiovascular risk
factors over time, from pregnancy to
manifestation of cardiovascular disease,
needs more evaluation. Most studies
have focused on cardiovascular risk fac-
tors short-term postpartum or more
than 20 years after pregnancy.7 More
research is needed in the fourth and fth
decade of life, when premature cardio-
vascular diseases are expected to
develop.7 It could be suggested that
women with a history of preeclampsia
could benet highly from screening for
cardiovascular disease in these decades
of life. Screening would be best, however,
if cardiovascular disease has not already

MONTH 2017 American Journal of Obstetrics & Gynecology 1.e1

Original Research
FIGURE 1
Recruitment study population
Bokslag et al. Long-term cardiovascular risk after preeclampsia. Am J Obstet Gynecol 2017.
developed. Studies focusing on risk fac-
tor screening in this time window after
pregnancy are lacking, and as a conse-
quence, it is not clear what the most
optimal timing for screening and pre-
ventive measures is.
The question this study addresses is: is
there still a window of opportunity for
preventive measures in the fth decade
of life, or has cardiovascular disease
already developed? To clarify this fragile
balance, this study investigated cardio-
vascular risk factors in women with a
history of early-onset preeclampsia
compared to women with a history of an
uncomplicated pregnancy in the fth
decade of life.
Materials and Methods
Study population
All women were recruited from obstet-
rical databases of 2 tertiary medical
centers in the Netherlands, all giving
birth between 1998 and 2005. Medical
records of women with a history of early-
onset preeclampsia were screened
consecutively, and all eligible women
were invited. Participating women with a
history of early-onset preeclampsia were
1.e2 American Journal of Obstetrics & Gynecology MONTH 2017
OBSTETRICS
matched with women with an uncom-
plicated pregnancy, for maternal age
(range  5 years) and date of delivery
(range  1 year). Early-onset pre-
eclampsia was diagnosed as delivery
before 34 weeks gestation, blood pres-
sure
140/90 mm Hg, and proteinuria

300 mg/24 h by use of the Interna-
tional Society for the Study of Hyper-
tension in Pregnancy ISSHP 2001
criteria, the criteria used at the time of
diagnosis of the study population.8
Preeclampsia was dened as severe
in the presence of 1 or more of
the following conditions: proteinuria
5
g/24 h, HELLP (ie, Hemolysis, Elevated
Liver enzymes, and Low Platelet count)
syndrome, occurrence of eclamptic
seizure, or pulmonary edema.
An uncomplicated pregnancy history
was dened as giving birth between 37
and 42 weeks gestation after a normo-
tensive pregnancy and with absence of
intrauterine growth restriction. For
women with both a history of early-
onset preeclampsia and uncomplicated
pregnancy, exclusion criteria were
established chronic hypertension, use of
antihypertensive medication or blood
ajog.org
pressure at booking, the rst blood
pressure measured in rst trimester,

140/90 mm Hg; diabetes mellitus or
gestational diabetes; cardiovascular dis-
eases, including renal diseases, Raynaud
disease as a possible reection of
impaired vascular function, or the use of
cardiovascular related medication before
index pregnancy; multiple pregnancies;
congenital abnormalities; pregnant at, or
the last 6 months before, assessment; and
breastfeeding at time of assessment.
Consenting participants were invited
between 2014 and 2016 for a cardiovas-
cular risk assessment at the VU Univer-
sity Medical Center. Approval for the
study was obtained from the medical
ethics committee of the VU University
Medical Center in Amsterdam and
locally by the hospital board of the Ac-
ademic Medical Centre Amsterdam
(protocol approval: NL38972.029.12;
Dutch trial registration: NTR5297).
Measures
All participants were asked to ll in a
questionnaire that included smoking
status, obstetric history, family history
regarding cardiovascular diseases, cur-
rent medical conditions, and use of
medication. The part of the question-
naire regarding medical conditions
contained questions about treatment by
a medical specialist, type of specialist, for
what diagnosis; and presence and/or
treatment of cardiovascular risk factors
or cardiovascular diseases including
diabetes, increased cholesterol, stroke,
high blood pressure, heart attack, coro-
nary artery disease, and heart failure.
The cardiovascular risk assessment
consisted of blood pressure measure-
ment, anthropometrics, blood sampling,
and urine collection. Blood pressure was
measured twice manually with the pa-
tient in a sitting position. The rst and
fth phase Korotkoff sounds were used
for systolic and diastolic blood pressure.
The mean value of 2 measurements was
used.
Body height was measured with a
wall-mounted stadiometer at 0.5 cm
precision with the subject not wearing
shoes. Body weight was measured with a
mechanical scale at 0.5 kg precision in
light indoors with the subject clothed
ajog.org OBSTETRICS Original Research

without shoes. Body mass index was

TABLE 1
calculated as body weight divided by the
Baseline characteristics at index pregnancy
square of the body height (kg/m2). Waist
and hip circumference was measured on Early-onset Uncomplicated
uncovered skin with an inelastic tape preeclampsia pregnancy
measure at the narrowest point of the Characteristics n 131 n 56 P value
waist and the widest part of the hips to Maternal age, y 30.9  5.0 32.3  4.1 .046
the nearest 0.5 cm. Waist-hip-ratio was Primiparous 101 (77.1) 29 (51.8) .001
calculated as waist circumference
Blood pressure
divided by hip circumference (cm/cm).
The venous blood samples were taken SBP at booking,a mm Hg 117  10.2 109  9.9 <.0001
after an overnight fast for analysis of DBP at booking,a mm Hg 72  7.9 65  7.0 <.0001
lipids, lipoproteins, glucose, glycated Highest SBP, mm Hg 182  22.0 123  9.2 <.0001
hemoglobin, renal function, and N-ter-
Highest DBP, mm Hg 115  8.2 75  5.9 <.0001
minal brain natriuretic peptide. Imme-
b
diately after the patient woke up, urine Severity
was collected at home for micro- Proteinuria
5 g/24h 59 (45.0)  
albuminuria assessment. HELLP syndrome 43 (32.8)  
The window of opportunity for pre-
Eclampsia 10 (7.6)  
ventive measures was dened as presence
of the cardiovascular risk factors hyper- Pulmonary edema 6 (4.6)  
tension and/or metabolic syndrome but Outcome
in absence of the established cardiovas- Gestational age at delivery, wk 30.5  2.1 40.0  1.4 <.0001
cular diseases myocardial infarction and
Caesarean delivery 119 (90.8) 9 (16.1) <.0001
stroke. These cardiovascular diseases
were chosen to be reliable in self-report.9 Birth weight, g 1136  362 3571  440 <.0001
Hypertension was dened as either Fetal sex, girls 77 (58.8) 27 (48.2) .201
current use of antihypertensive medica- Fetal death 18 (13.7) 0 .002
tion and/or blood pressure
140/90 mm
Placental weight, g 226  81 644  125 <.0001
Hg measured at risk assessment.10
Metabolic syndrome was diagnosed Values are mean  SD or n (%).

according to the Adult Treatment Panel
III criteria. Metabolic syndrome was
dened as the presence of 3 or more of
the following characteristics: waist
circumference >88 cm, triglyceride
levels
1.7 mmol/L, high-density lipo-
protein cholesterol <1.29 mmol/L,
blood pressure
130/85 mm Hg, and
fasting glucose levels
5.7 mmol/L.11
Sample size calculation
In addition the cardiovascular risk
assessment, an evaluation of diastolic
function by ultrasound was carried out
in the study population. The sample size
calculation was based on data of the
prevalence of diastolic dysfunction in a
randomly recruited European popula-
tion.12 To detect the expected difference
in prevalence of 10%, with a power of
80% and a 2-sided a of 0.05, we needed
137 women in both groups. Because
diastolic dysfunction, and its associated
signs measured by ultrasound, was never
reported long term after preeclampsia,
DBP, diastolic blood pressure; HELLP, Hemolysis, Elevated Liver enzymes, and Low Platelet count; SBP, systolic blood pressure.
a
First blood pressure measured in pregnancy, all in the first trimester; b Multiple conditions possible.
Bokslag et al. Long-term cardiovascular risk after preeclampsia. Am J Obstet Gynecol 2017.
an interim analysis was performed when distributed numerical data, and as per-
all women with a history of early-onset centages for categorical data. Differences
preeclampsia were included, at a 2:1 ra- were analyzed by unpaired t test, Mann-
tio (early-onset preeclampsia vs healthy Whitney U test, and the Fisher exact test
pregnancy). At interim analysis, a sig- when appropriate. In all analyses, a P <
nicant difference on diastolic function .05 was considered statistically signi-
was observed between both groups (P < cant. Data were analyzed with SPSS 22
.0001); therefore, the study population software (IBM Corp, Armonk, NY).
was completed. A total number of 131
women with a history of early-onset Results
preeclampsia and 56 women with a his- The baseline characteristics at index
tory of an uncomplicated pregnancy pregnancy are described in Table 1.
participated in the cardiovascular risk Women with a history of early-onset
assessment study (Figure 1). preeclampsia were younger at delivery
(P .046), more often were primiparous
Statistical analyses (P .001), and more often delivered via
Characteristics were reported as means caesarean delivery (P <.0001) compared
with standard deviations for normal with women with an uncomplicated
distributed numerical data, medians pregnancy history. As expected, the
with interquartile ranges for not normal women with former early-onset

MONTH 2017 American Journal of Obstetrics & Gynecology 1.e3

Original Research
TABLE 2
Characteristics at cardiovascular risk assessment 9L16 years after index
pregnancy
Characteristics
Age, y
Time postindex pregnancy, years
White
Current smoking
Obstetric history
Preeclampsia in other pregnancy
Stillbirth in history
a
Family history
Hypertensive pregnancy disorder
Myocardial infarction
Stroke
Values are mean  SD or n (%).
a
Family history: only first-degree relatives mentioned.
Bokslag et al. Long-term cardiovascular risk after preeclampsia. Am J Obstet Gynecol 2017.
preeclampsia had greater blood pres-
sures during pregnancy (P < .0001). In
addition, they had a shorter gestational
age (P < .0001), children with lower
birth weight (P < .0001), and lower
placental weight (P < .0001). Of the
women with a history of early-onset
preeclampsia, 86 (66%) had a severe
disease.
Table 2 presents the characteristics of
the participants at risk assessment 916
years after their index pregnancy.
Women with a history of early-onset
preeclampsia were younger (mean dif-
ference 2.5 years, P .004) and the time
between pregnancy and risk assessment
was shorter (mean difference 1.1 year,
P .003). They more often had rst-
degree relatives with a hypertensive
pregnancy disorders (P .03) and stroke
(P .002). Having a rst-degree relative
with myocardial infarction was similar in
both groups.
All results from the cardiovascular risk
assessment are shown in Table 3. Women
with a history of early-onset pre-
eclampsia had signicantly greater blood
pressures, both systolic and diastolic,
and mean arterial blood pressure was
increased (all P < .0001). Regarding
1.e4 American Journal of Obstetrics & Gynecology MONTH 2017
OBSTETRICS ajog.org
uncomplicated pregnancy in history,
14.3% (P .001). Of these women, all
were diagnosed with increased blood
pressure at risk assessment, and none
Early-onset Uncomplicated used antihypertensive medication.
preeclampsia, pregnancy, Metabolic syndrome was present in
n 131 n 56 P value 16.8% of the women with a history of
44.0  5.6 46.5  4.8 .004 early-onset preeclampsia and in 1.8% of
13.1  2.2 14.2  2.3 .003 the women with a history of uncompli-
cated pregnancy, a signicant difference
113 (86.3) 49 (87.5) 1.000
(P .003).
23 (17.6) 9 (16.1) 1.000
Comment
25 (19.1)   Women with a history of early-onset
preeclampsia who were in the fth
12 (9.2) 1 (1.8) .113
decade of life had high rates of cardio-
vascular risk factors, although cardio-
27 (20.6) 4 (7.1) .030 vascular diseases had not developed yet.
As a result, the women could still benet
37 (28.2) 19 (33.9) .459
from measures preventing cardiovascu-
26 (19.8) 4 (7.1) .002 lar disease. We conclude that there is a
window of opportunity for preventive
measures in women in their forties, for
those who have a history of early-onset
preeclampsia (42%).
We have found that 38.2% of
anthropometrics, they had greater body women with early-onset preeclampsia
mass index (P .006), greater waist in history had hypertension 916 years
circumference (P .007), and more after pregnancy, at an average age of 44
often had an increased waist-to-hip ratio years (SD  5.6). Lower rates of hy-
(P .041). Biomarker analyses revealed pertension were found in studies
lower levels of high-density lipoprotein investigating women with early-onset
(P .001) and greater levels of triglyc- preeclampsia in the rst year after
eride, glycated hemoglobin, and micro- pregnancy, 2225%.13,14 Nine years
albumin in urine (P values .005, <.0001, after pregnancy, at a mean age of 39
and .015, respectively) compared with years (SD  4.9), Drost et al15 found a
women with an uncomplicated preg- prevalence of hypertension of 43.1%,
nancy history. which was comparable with our study.
In total, 42% of the women with The prevalence of hypertension in the
former preeclampsia met the criteria for general Dutch female population be-
the window of opportunity for preven- tween 40 and 49 years old is 15%,
tive measures by having hypertension or similar to the observed prevalence in
metabolic syndrome in absence of our participants with a history of an
established cardiovascular diseases. This uncomplicated pregnancy.16 The rate
was signicantly greater than in women of hypertension in our participants
with an uncomplicated pregnancy in with a history of early-onset pre-
history, of whom 14.3% met the criteria eclampsia was comparable with that of
(P < .0001). Dutch women between 50 and 59 years
Of the women with early-onset pre- old (32%).16 Therefore, women with
eclampsia in history, 38.2% was diag- early-onset preeclampsia seemed to
nosed with hypertension. This was have a cardiovascular state of women
specied by use of antihypertensive 10 years older. This nding is in line
medication in 17.6% and increased with the study of Heida et al,17 who
blood pressure at risk assessment in found that the mean age of onset of
28.2%. Hypertension was diagnosed chronic hypertension after a hyper-
signicantly less often in women with an tensive pregnancy disorder was 43.5
ajog.org OBSTETRICS Original Research

TABLE 3
Cardiovascular risk assessment 9L16 years after index pregnancy
Early-onset preeclampsia Uncomplicated pregnancy
Characteristics n 131 n 56 P value
Anthropometrics
SBP, mm Hg 126  18.6 115  17.0 <.0001
DBP, mm Hg 82  9.8 74  9.4 <.0001
MAP, mm Hg 96.7  11.8 87.4  11.3 <.0001
2
BMI, kg/m 25.6 [22.728.9] 23.9 [21.226.6] .006
BMI > 25 kg/m2 71 (54.2) 24 (42.9) .201
Waist circumference, cm 79.0 [75.090.0] 77.0 [71.082.8] .007
Waist-Hip-ratio >0.80 38 (29.0) 8 (14.3) .041
Biomarkers
Cholesterol, mmol/L 4.9 [4.25.6] 5.2 [4.55.8] .150
HDL, mmol/L 1.53 [1.291.91] 1.78 [1.522.18] .001
LDL, mmol/L 2.8 [2.33.3] 2.9 [2.33.4] .702
TC/HDL ratio 2.95 [2.563.85] 2.80 [2.343.39] .054
Triglycerides, mmol/L 1.0 [0.71.4] 0.8 [0.71.1] .005
Glucose, mmol/mL 5.1 [4.95.4] 5.1 [4.85.3] .173
HbA1c, mmol/mol 36 [3338] 33 [3236] <.0001
2
eGFR, mL/min/1.73 m 90 [8290] 90 [8290] .805
NT-proBNP, ng/L 51 [2878] 52 [3186] .573
Microalbumin in urine, g/mol creatinine 4.4 [3.07.8] 3.0 [3.03.9] .015
Cardiovascular implication
Cardiovascular risk factora 55 (42.0) 8 (14.3) <.0001
Hypertensionb 50 (38.2) 8 (14.3) .001
Use of antihypertensive medication 23 (17.6) 0 <.0001
SBP
140 and/or DBP
90 mm Hg 37 (28.2) 8 (14.3) .042
Metabolic syndrome 22 (16.8) 1 (1.8) .003
Healthy at risk assessmentc 76 (58.0) 48 (85.7) <.0001
Values are mean  SD, n (%), or median [IQR].
BMI, body mass index; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; HbA1c, glycated haemoglobin; HDL, high-density lipoprotein; IQR, interquartile range; LDL, low-
density lipoprotein; MAP, mean arterial pressure; NT-proBNP, n-terminal prohormone of brain natriuretic peptide; SBP, systolic blood pressure; TC, total cholesterol.
a
Presence of hypertension and/or metabolic syndrome; b Current use of antihypertensive medication and/or blood pressure
140/90 mm Hg at risk assessment; c Absence of cardiovascular
risk factors.
Bokslag et al. Long-term cardiovascular risk after preeclampsia. Am J Obstet Gynecol 2017.

years compared with 51.2 years after a
normotensive pregnancy.
Guidelines concerning cardiovascular
health in women mention the increased
cardiovascular risk after hypertensive
pregnancy disorders, but well-founded
recommendations for when to start
screening, interval and prevention
are lacking.18-20 Our results suggest that
a cardiovascular risk assessment as
preventive measure might be opportune
in the fth decade of life.
Van Rijn et al13 and Drost et al15
investigated women 9 months and 10
years after early-onset preeclampsia. In
both studies, in different phases of life,
the observed prevalence of metabolic
syndrome was similar to our observation
(15.2%, 18%, and 16.8% respectively).
In contrast to our study, Hermes et al21
investigated women with term pre-
eclampsia (>36 weeks of gestation)
along with term gestational hyperten-
sion and compared with healthy preg-
nancies, 2.5 years postpartum. They
found a prevalence of 25%, which was
greater than in our population. These
ndings might suggest that metabolic
syndrome is increased in women with a
history of hypertensive pregnancy

MONTH 2017 American Journal of Obstetrics & Gynecology 1.e5

Original Research OBSTETRICS
disorder, irrespective of the severity of
the condition. This also is stated by
Veerbeek et al,22 who found similar
prevalence rates of metabolic syndrome
in early-onset preeclampsia, late-onset
preeclampsia, and pregnancy-induced
hypertension, 0.5 to 2.5 years
postpartum.
We performed an extensive risk
assessment in a large cohort of women,
for all of whom we had obstetrical data.
The major strength of our study was that
we examined women with a history of
early-onset preeclampsia in their forties,
so in the fth decade of life. Our study
has some limitations, however. It should
be noted that measuring blood pressure
twice in 1 visit might have overstate the
rate of hypertension, compared with
measuring blood pressure at 2 or more
visits.23 Although the procedure was
similar for participants with pre-
eclampsia and uncomplicated pregnancy
in history, this procedure also was
similar to the one used in studies to
which we compared our data.13-15 For
that reason, we believe that the prag-
matically chosen procedure 2 measures
in 1 visit did not affect the results
considerably. The response rates in both
groups were low, 53% in the early-onset
preeclampsia group and 26% in the un-
complicated pregnancy group. This was
mainly the result of that we could not
locate the potential participants; many
addresses were outdated 916 years after
pregnancy. In total, 43 women in the
early-onset preeclampsia group and 26
women in the uncomplicated pregnancy
group actually declined participation. It
might be conceivable that from all
women with a history of early-onset
preeclampsia, the women with most se-
vere disease in pregnancy were more
willing to participate. Because earlier
onset of preeclampsia is associated with
greater cardiovascular risk, this might
induce some selection bias, which can
overstate the difference we have found.
Furthermore, women who had a
reason to be examined or reassured on
their cardiovascular state, for example,
positive family history of myocardial
infarction, high body mass index, or
smoking, would be more willing to
participate in a cardiovascular risk
1.e6 American Journal of Obstetrics & Gynecology MONTH 2017
assessment study. Because this applied to
all participants, the difference found
between both groups would not have
been remarkably affected. In addition,
age differed signicantly between both
groups. Women with an uncomplicated
pregnancy history were on average 2.5
years older. We could not explain why
relatively older women were more
willing to participate. Because advanced
age is associated with increased risk of
cardiovascular disease, this could result
in an underestimation of the difference
of risk factors between both groups. It
should be noted, however, that the ab-
solute difference in age might not be
clinically relevant.
Several prediction models exist to
calculate the long-term risk of devel-
oping cardiovascular disease, but none of
these models were validated for women
with a history of preeclampsia. The use
of the standard prediction models in
these women might not be appropriate.
Therefore, future research should focus
on moderation and validation of these
models before use in women with a
history of preeclampsia.
To determine whether preventive
measures can indeed reduce the devel-
opment of cardiovascular disease in this
specic patient group, more research is
necessary. For example, reduction of
blood pressure is proven to be benecial
to reduce cardiovascular events in all
ages in the general population, but these
interventions are not examined specif-
ically in women with a history of pre-
eclampsia.24 Lifestyle interventions
(diet, exercise, smoking cessation,
alcohol intake reduction) have been
studied in the general population and in
postpartum women, but not in women
with a history of preeclampsia. The
current focus of lifestyle intervention
studies in postpartum women is on the
rst year postpartum25; however, long-
term effects studies also should focus
on women in the fourth and fth decade
of life, when rst signs of cardiovascular
disease are expected to occur.
In conclusion, women who experi-
enced early-onset preeclampsia are still
in the window of opportunity for pre-
ventive measures in the fth decade of
their life. These women have important
ajog.org
modiable risk factors for cardiovascular
diseases but are currently outside the
scope of most preventive programs
because of their relatively young age. n
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Author and article information
From the Departments of Obstetrics and Gynecology (Drs
Bokslag, Teunissen, van Kesteren, and de Groot), Phys-
iology (Drs Franssen and Paulus), and Cardiology
(Dr Kamp), VU University Medical Center, Amsterdam,
The Netherlands; Department of Educational Develop-
ment and Research, Faculty of Health, Medicine and Life
Sciences, Maastricht University, Maastricht, The
Netherlands (Dr Teunissen); Department of Cardiology,
Antwerp University Hospital, Antwerp, Belgium
(Dr Franssen); and Heart Center (Dr van Kesteren) and
Department of Obstetrics and Gynecology (Dr Ganze-
voort), Academic Medical Center, Amsterdam, The
Netherlands.
Received Nov. 14, 2016; revised Jan. 13, 2017;
accepted Feb. 6, 2017.
The authors report no conflict of interest.
This research was funded, in part, by a grant from the
Dutch Heart Association.
Corresponding author: Anouk Bokslag. a.bokslag@
vumc.nl
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