Cardiovascular Outcomes After Preeclampsia
or Eclampsia Complicated by Myocardial
Infarction or Stroke
Mary Downes Gastrich, PhD, EDD, Sampada K. Gandhi, MBBS, MPH, John Pantazopoulos, MD,
Edith A. Zang, PhD, Nora M. Cosgrove, RN, Javier Cabrera, PhD, Jeanine E. Sedjro, MS,
Gloria Bachmann, MD, and John B. Kostis, MD, for the Myocardial Infarction Data Acquisition
Downloaded from https://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3Gamkn0m7hy4hlV2NsYU8tWfn6hUp1T6LQSMnF2cpWJE= on 08/13/2018
System (MIDAS 17) Study Group
OBJECTIVE: To assess the relationship between pre-
eclampsia or eclampsia and stroke, myocardial infarction
(MI), subsequent cardiovascular outcomes, and long-
term survival.
METHODS: Using the Myocardial Infarction Data Acquisi-
tion System in New Jersey (1994 –2009), we analyzed car-
diovascular outcomes in women with and without pre-
eclampsia or eclampsia and a first MI or stroke but with a
hospitalization for a first MI or stroke (analysis 1: MI case
group, nⴝ57; MI control group, nⴝ155; stroke case group,
nⴝ132; stroke control group, nⴝ379). We also compared
these outcomes in women with preeclampsia or eclampsia
and a first MI or stroke during pregnancy with women with
preeclampsia or eclampsia without MI or stroke during
pregnancy (analysis 2: MI case group, nⴝ23; MI control
group, nⴝ67; stroke case group, nⴝ90; stroke control
group, nⴝ263). A subsequent occurrence of MI, stroke, and
cardiovascular death, as well as a combined cardiovascular
outcome, was ascertained.
RESULTS: In analysis 1, women with preeclampsia or
eclampsia were at significantly lower risk for combined
cardiovascular outcome with all deaths (frequency of
outcome 16.7%) and with cardiovascular deaths (10.6%)
From the Department of Obstetrics/Gynecology and Reproductive Sciences and
the Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School,
New Brunswick, New Jersey; Rutgers University, Piscataway, New Jersey.
The Myocardial Infarction Data Acquisition System was supported by Robert
Wood Johnson Foundation, Princeton, New Jersey, and ID 57787 by Schering
Plough Foundation, Kenilworth, New Jersey.
Corresponding author: Mary D. Gastrich, PhD, EDD, Department of Obstetrics
and Gynecology and Reproductive Sciences, UMDNJ-Robert Wood Johnson
Medical School, 125 Paterson Street, CAB Room 2105, New Brunswick, NJ
08901; e-mail: gastrimd@umdnj.edu.
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2012 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/12
VOL. 120, NO. 4, OCTOBER 2012
compared with women without preeclampsia or eclamp-
sia after a first stroke (33.8% and 23.5%, respectively). In
analysis 2, women with preeclampsia or eclampsia and a
first stroke during admission were at significantly higher
risk of all death (11.1%) and the combined cardiovascular
outcome with all deaths (11.1%) compared with women
with preeclampsia or eclampsia without a stroke (1.9%
and 2.7%, respectively) during that admission.
CONCLUSION: Our study indicates that preeclampsia
or eclampsia not complicated by MI or stroke during
pregnancy may not confer a very high risk for subsequent
MI and stroke in up to 16 years of follow-up. Our data
suggest that other known risk factors put women at
greater risk for stroke than preeclampsia or eclampsia
complicated by a stroke.
(Obstet Gynecol 2012;120:823–31)
DOI: http://10.1097/AOG.0b013e31826ae78a
LEVEL OF EVIDENCE: II
W omen who have had preeclampsia or eclampsia
are at increased risk for cardiovascular (cardio-
vascular) disease compared with pregnant women with-
out preeclampsia or eclampsia.1–3 Studies have linked
preeclampsia or eclampsia with later life myocardial
infarction (MI),1,4 –7 stroke,5,8 –12 death,6,11,13 and coronary
heart disease.14,15 Data are lacking on the long-term
cardiovascular outcomes of women with preeclampsia or
eclampsia who experienced a first MI or stroke during or
after hospitalization for preeclampsia or eclampsia. The
purpose of this study was to assess the subsequent occur-
rence of MI, stroke, or cardiovascular death after the first
admission of MI and stroke in these women.
MATERIALS AND METHODS
Using a matched case-control design, women with
preeclampsia or eclampsia diagnosed were identified
OBSTETRICS & GYNECOLOGY 823
using the Myocardial Infarction Data Acquisition Sys-
tem and were followed-up for cardiovascular outcomes
and survival.
The objective was to assess the relationship be-
tween the medical conditions of preeclampsia or
eclampsia, stroke, and MI by assessing cardiovascular
outcomes. We compared four groups (Fig. 1). In
analysis 1, we estimated the effect of preeclampsia or
eclampsia by comparing women with preeclampsia
or eclampsia (case 1) with a first MI and stroke
diagnosis when the MI and stroke event occurred
either on admission for preeclampsia or eclampsia or
afterward and women without documented pre-
eclampsia or eclampsia and a first MI and stroke
(control 1). To estimate the effect of a first MI and
stroke event accompanying preeclampsia or eclamp-
sia, we conducted analysis 2, which further evaluated
all women with preeclampsia or eclampsia by com-
paring women with preeclampsia or eclampsia with a
first MI and stroke on admission for preeclampsia or
eclampsia only (pregnancy-related), which repre-
sented the most severe case (case 2) and women with
preeclampsia or eclampsia and no MI or stroke on
preeclampsia or eclampsia admission (control 2). We
compared the occurrence of the subsequent com-
bined cardiovascular outcomes in these four groups
defined as the first occurrence of hospital admission
for MI or stroke or death attributable to a cardiovas-
cular cause. The two case groups were matched to the
respective control groups by age and year of dis-
charge from the hospital. In each analysis, separate
assessments were performed for MI and stroke.
Women in all groups were followed-up for up to16
years in the Myocardial Infarction Data Acquisition
System database.
Our data source was the Myocardial Infarction
Data Acquisition System, which contains hospital
records of all patients admitted to nonfederal hospi-
tals in New Jersey with a cardiovascular disease
diagnosis or procedure. The information from the
Myocardial Infarction Data Acquisition System data-
base including the diagnoses has been previously
validated using a random sample of 726 medical
charts.16,17 In addition, a random chart review per-
formed for patients with stroke showed 89.5% speci-
ficity for diagnosis of stroke. The New Jersey State
Institutional Review Board and the University of
Medicine and Dentistry of New Jersey Institutional
Review Board approved the study with waiver of
consent.
The selection of case and control group partici-
pants included a total of 6,628 women (13–54 years,
mean⫾standard deviation 31.2⫾6.4) who were ad-
mitted for the first time with a primary diagnosis

Case 1
Control 1
(A+B)

Preeclampsia or eclampsia Cardiovascular outcome First MI or stroke; no preeclampsia Cardiovascular outcome

and first MI or stroke diagnoses MI or eclampsia diagnosis before or MI
on the same admission Stroke after the first MI or stroke Stroke
n=57/132 Death (all causes) n=155/379 Death (all causes)
Death (cardiovascular cause) Death (cardiovascular cause)

A B C A C

First MI or stroke after admission

for preeclampsia or eclampsia
A
Case 2 Control 2
(only A)

Preeclampsia or eclampsia Cardiovascular outcome Admission for preeclampsia or Cardiovascular outcome

and first MI or stroke diagnoses MI eclampsia and no MI or stroke MI
on the same admission Stroke on the same admission Stroke
n=23/90 Death (all causes) n=67/263 Death (all causes)
Death (cardiovascular cause) Death (cardiovascular cause)

A C A C

B
Fig. 1. Description of the myocardial infarction and stroke study groups. A and B, an index or a first event; C, a subsequent
cardiovascular outcome. Arrows indicate the direction of follow-up. Women in the case 1 (A) group were identified at time
points A and B; women in the case 2 group (B) were identified only at time point A.
Gastrich. Outcomes in Women With Preeclampsia or Eclampsia. Obstet Gynecol 2012.

824 Gastrich et al Outcomes in Women With Preeclampsia or Eclampsia OBSTETRICS & GYNECOLOGY
(reason for admission) or secondary diagnosis of
preeclampsia or eclampsia (International Classifica-
tion of Diseases, 9th Revision, Clinical Modification
[ICD-9-CM] codes 642.3– 642.7) from years 1994 to
2009. A description of the case and control group
participants used in both analyses is provided in
Figure 1. An ICD-9-CM code of 410 was used to
identify a diagnosis of MI, whereas ICD-9-CM codes
430, 431, 433.X1, 434.X1, 437.4, and 437.6 were used
to identify stroke. Up to three control group partici-
pants were selected from the eligible pool by match-
ing to the case group participant’s age and year of
discharge. If a control group participant of the same
age or discharge year as the case group participant
was not available, then a control group participant ⫾2
years in age or discharge year was selected. In MI and
stroke analyses, case group participants with MI and
stroke diagnoses and history of malignant neoplasm
before the preeclampsia or eclampsia admission were
excluded.
Patient characteristics included age, race, primary
insurance, and source of admission, which were avail-
able in the Myocardial Infarction Data Acquisition
System database. We examined the presence of the
comorbid conditions recorded either at or before the
admission for the first or index event using ICD-
9-CM codes for diabetes mellitus, renal disease, car-
diac dysrhythmia, anemia, obesity, hyperlipidemia,
systemic lupus erythematosus, and hypercoagulable
state. We also examined the presence of chronic
hypertension recorded before the preeclampsia or
eclampsia admission using ICD-9-CM codes.
The ascertainment of death was obtained from
death information (date and cause of death) by match-
ing the Myocardial Infarction Data Acquisition Sys-
tem records to New Jersey death registration files
using a public automated and previously validated
record linkage and consolidation software (The Link
King).18 Deaths were classified into two categories:
cardiovascular death and noncardiovascular death.
In both analyses, time to the combined cardio-
vascular outcome (MI, stroke, cardiovascular death)
was calculated as the number of days from the index
event date to the admission date of the cardiovascular
outcome (MI or stroke) or the date of death, which-
ever occurred first. If a case group participant or
control group participant did not experience any of
the cardiovascular outcomes or death, then she was
followed-up from the index event to December 31,
2009. In addition to the combined cardiovascular
outcome, time to the individual components of the
combined cardiovascular outcome (admission for MI,
admission for stroke, cardiovascular death) was sepa-
VOL. 120, NO. 4, OCTOBER 2012 Gastrich et al
rately calculated as the number of days from the
index event to the occurrence of the cardiovascular
outcome. When the outcome of interest was MI or
stroke, women who died of any cause before experi-
encing that outcome were censored on the date of
their death. When the outcome of interest was cardio-
vascular death, patients who died of noncardiovascu-
lar-related causes were censored on the date of their
death.
Patient characteristics and the frequencies of each
outcome were summarized by case or control status in
each analysis group. Event rates were calculated using
Cox proportional hazards regression models. Models
were adjusted for race, primary insurance, obesity,
and history of diabetes mellitus in analysis 1, and for
race, primary insurance, and obesity in analysis 2.
The reason for adjustments was to avoid bias in the
comparison of case and control group participants
because their baseline characteristics differed be-
tween the groups. The Cox models also were adjusted
for the matching by stratifying by age and discharge
year. In each Cox model, event rates were compared
between case and control group participants through
a hazard ratio (HR) with 95% confidence intervals
(CIs), and the Kaplan-Meier survival product limit
estimates for the “combined cardiovascular outcome”
were plotted over time separately for case and control
group participants. In both analysis 1 and analysis 2,
a sensitivity analysis was performed by replacing
cardiovascular deaths with all-cause deaths to explore
whether this change had an effect on the outcome.
We conducted two additional analyses: a subgroup
analysis to explore the potential difference in event
rates between younger and older women, using the
median age as the cut-off, and an analysis of the risk
of admission for heart failure separately and as part of
the combined cardiovascular outcome. The results of
the latter sensitivity analyses are presented in the
Appendix (available online at http://links.lww.com/
AOG/A318). All statistical analyses were performed
using SAS/STAT software 9.3.
RESULTS
Analysis 1 included comparison of case group partic-
ipants with preeclampsia or eclampsia and anytime
occurrence of a first MI and stroke with control group
participants with a first MI and stroke and without a
documented history of preeclampsia or eclampsia.
Patient characteristics are presented in Table 1. A
higher percentage of control group participants in
both the MI and stroke study groups were admitted
from an emergency department compared with case
group participants. In the MI study group, as well as
Outcomes in Women With Preeclampsia or Eclampsia 825
Table 1. Patient Characteristics by Study Groups
Analysis 1: Comparison of Women Analysis 2: Comparison of Women With
Without Preeclampsia or Eclampsia Preeclampsia or Eclampsia
MI Study Stroke Study MI Study Stroke Study
Group (n ⴝ 212) Group (n ⴝ 511) Group (n ⴝ 90) Group (n ⴝ 353)
Control
Patient Characteristics Case 1 Control 1 Case 1 Control 1 Case 2 2 Case 2 Control 2

Women 57 (26.9) 155 (73.1) 132 (25.8) 379 (74.2) 23 (25.6) 67 (74.4) 90 (25.5) 263 (74.5)
Age group (y)
16–30 11 (19.3) 19 (12.3) 48 (36.4) 127 (33.5) 6 (26.1) 16 (23.9) 43 (47.8) 124 (47.1)
31–40 24 (42.1) 70 (45.2) 62 (47) 186 (49.1) 14 (60.9) 42 (62.7) 40 (44.4) 119 (45.3)
41–51 22 (38.6) 66 (42.6) 22 (16.7) 66 (17.4) 3 (13) 9 (13.4) 7 (7.8) 20 (7.6)
Race*
White 25 (43.9) 83 (53.5) 59 (44.7) 169 (44.6) 11 (47.8) 31 (46.3) 43 (47.8) 161 (61.5)
Black 23 (40.4) 54 (34.8) 54 (40.9) 157 (41.4) 8 (34.8) 30 (44.8) 34 (37.8) 87 (33.2)
Other 9 (15.8) 18 (11.6) 19 (14.4) 53 (14) 4 (17.4) 6 (9) 13 (14.4) 14 (5.3)
Source of admission*
Emergency department 31 (55.3) 133 (85.8) 73 (58.4) 285 (78.9) 7 (30.4) 7 (10.4) 38 (45.8) 11 (4.5)
Nonemergency department 19 (33.9) 13 (8.4) 46 (36.8) 51 (14.1) 15 (65.2) 59 (88.1) 41 (49.4) 231 (93.9)
Transfer from another 6 (10.7) 9 (5.8) 6 (4.8) 25 (6.9) 1 (4.3) 1 (1.5) 4 (4.8) 4 (1.6)
hospital, skilled nursing
facility, or health care
facility
Primary insurance
Commercial 41 (71.9) 101 (65.2) 101 (76.5) 226 (59.6) 15 (65.2) 57 (85.1) 70 (77.8) 230 (87.4)
Government 9 (15.8) 39 (25.2) 18 (13.6) 109 (28.8) 5 (21.7) 8 (11.9) 13 (14.4) 26 (9.9)
Self-pay 7 (12.3) 15 (9.7) 13 (9.8) 44 (11.6) 3 (13) 2 (3) 7 (7.8) 7 (2.7)
Comorbidities
Chronic hypertension 14 (24.6) 96 (61.9) 15 (11.4) 157 (41.4) 3 (13) 33 (49.3) 3 (3.3) 84 (31.9)
Cardiac dysrhythmia 17 (29.8) 42 (27.1) 12 (9.1) 46 (12.1) 4 (17.4) 10 (14.9) 4 (4.4) 38 (14.4)
Diabetes mellitus 15 (26.3) 65 (41.9) 11 (8.3) 84 (22.2) 2 (8.7) 4 (6) 3 (3.3) 17 (6.5)
Renal disease 10 (17.5) 47 (30.3) 7 (5.3) 61 (16.1) 1 (4.3) 4 (6) 3 (3.3) 8 (3)
Anemia 24 (42.1) 60 (38.7) 30 (22.7) 124 (32.7) 6 (26.1) 12 (17.9) 17 (18.9) 49 (18.6)
Hyperlipidemia 15 (26.3) 52 (33.5) 11 (8.3) 54 (14.2) 2 (8.7) 1 (1.5) 0 (0) 4 (1.5)
Obesity 9 (15.8) 34 (21.9) 13 (9.9) 63 (16.6) 0 (0) 14 (20.9) 2 (2.2) 19 (7.2)
Systemic lupus 1 (1.7) 2 (1.3) 6 (4.5) 24 (6.3) 0 (0) 1 (1.5) 2 (2.2) 3 (1.1)
erythematosus
†
Hypercoagulable state 1 (1.7) 0 (0) 0 (0) 9 (2.4) 0 (0) 0 (0) 0 (0) 2 (0.8)
MI, myocardial infarction.
Data are n (%).
* Missing information on race and source of admission.
†
We could not find International Classification of Diseases-9-Clinical Modification codes for hypercoagulable state in any of the
admissions for women from many subgroups.

in the stroke group, a higher percentage of control
group participants had a history of diabetes mellitus,
renal disease, obesity, and anemia compared with the
case group participants. The majority of women had
commercial insurance.
Results of the frequencies and adjusted risk of the
cardiovascular outcomes among case and control
group participants for the MI and stroke study groups
are presented in Table 2. In the MI study group, none
of the outcomes were significantly different between
case and control group participants after adjusting for
covariates. Figure 2A shows that there were no signif-
icant differences in the combined cardiovascular out-
come-free survival among case and control group
participants (P⫽.23). In the stroke study group, con-
trol group participants were at significantly higher risk
for the combined cardiovascular outcome with all-
cause and cardiovascular deaths compared with case
group participants (for all-cause deaths: absolute risk
in case group participants⫽0.167, absolute risk in
control group participants⫽0.338, absolute risk differ-
ence⫽0.171, number needed to treat⫽5.8; for cardio-
vascular deaths: absolute risk in case group partici-
pants⫽0.106, absolute risk in control group
participants⫽0.235, absolute risk difference⫽0.129,
number needed to treat⫽7.7). Figure 2B shows

826 Gastrich et al Outcomes in Women With Preeclampsia or Eclampsia OBSTETRICS & GYNECOLOGY
Table 2. Frequencies and Adjusted Risks of Cardiovascular Outcomes
Frequency of Frequency of Hazard Ratio
Outcomes in Outcomes in (95% CI) in Case
Study Group Cardiovascular Case Group Control Group or Control Group Wald ␹2
Type of Analysis (Total N) Outcome Participants, n (%) Participants, n (%) Participants P

Analysis 1: comparison MI (n⫽212) Case 1 (n⫽57) Control 1 (n⫽155)

with women without MI 3 (5.3) 15 (9.7) 1.55 (0.29–8.33) .61
preeclampsia or Stroke 1 (1.8) 12 (7.7) NA* NA*
eclampsia All deaths 5 (8.8) 31 (20.0) 0.53 (0.18–1.56) .25
CV deaths 2 (3.5) 12 (7.7) 0.94 (0.12–7.22) .95
Combined CV outcome 9 (15.8) 51 (32.9) 0.55 (0.25–1.22) .14
(with all deaths)
Combined CV outcome 6 (10.5) 35 (22.6) 0.54 (0.20–1.47) .23
(with CV deaths)†
Stroke Case 1 (n⫽132) Control 1 (n⫽379)
(n⫽511) Stroke 5 (3.8) 44 (11.6) 0.47 (0.17–1.27) .14
MI 2 (1.5) 14 (3.7) 0.48 (0.09–2.63) .40
All deaths 16 (12.1) 82 (21.6) 0.65 (0.37–1.15) .14
CV deaths 7 (5.3) 40 (10.5) 0.57 (0.24–1.36) .21
Combined CV outcome 22 (16.7) 128 (33.8) 0.57 (0.35–0.92) .02‡
(with all deaths)
Combined CV outcome 14 (10.6) 89 (23.5) 0.54 (0.30–0.98) .04‡
(with CV deaths)†
Analysis 2: comparison MI (n⫽90) Case 2 (n⫽23) Control 2 (n⫽67)
with women with MI 1 (4.4) 2 (3) NA* NA*
preeclampsia or Stroke 0 (0) 0 (0) NA* NA*
eclampsia All deaths 0 (0) 0 (0) NA* NA*
CV deaths 0 (0) 0 (0) NA* NA*
Combined CV outcome 1 (4.4) 2 (3) NA* NA*
(with all deaths)
Combined CV outcome 1 (4.4) 2 (3) NA* NA*
(with CV deaths)†
Stroke Case 2 (n⫽90) Control 2 (n⫽263)
(n⫽353) Stroke 0 (0) 0 (0) NA* NA*
MI 0 (0) 2 (0.8) NA* NA*
All deaths 10 (11.1) 5 (1.9) 10.7 (2.1–55.7) .005‡
CV deaths 4 (4.4) 1 (0.4) NA* NA
Combined CV outcome 10 (11.1) 7 (2.7) 8.91 (1.96–40.5) .005‡
(with All deaths)
Combined CV outcome 4 (4.4) 3 (1.1) NA* NA*
(with CV deaths)†
CI, confidence interval; MI, myocardial infarction; CV, cardiovascular; NA, not applicable.
Case 1: preeclampsia or eclampsia plus first MI or stroke.
Control 1: no preeclampsia plus first MI or stroke.
Case 2: preeclampsia plus MI or stroke on the same admission.
Control 2: preeclampsia, no MI, and stroke on the same admission.
* Model could not be fitted.
†
Primary combined CV outcome.
‡
Significant at P⬍.05.

that control group participants had a significantly
lower combined cardiovascular outcome-free survival
rate compared with case group participants (P⫽.04).
Results of the analysis by age groups indicated
that when the analyses for the MI study group were
performed separately for younger (39 years or
younger) and older (older than 39 years) women, MI
control group participants from the younger age
group were at significantly higher risk for all-cause
deaths (HR 5.91, 95% CI 1.31–26.67) and the com-
bined cardiovascular outcome with all-cause deaths
(HR 4.26, 95% CI 1.23–14.8) than case group partic-
ipants. No significant differences in the outcomes
were observed between case group participants and
control group participants older than age 39 years. In
the stroke study group, control group participants
were at significantly higher risk for all-cause death
(HR 2.36, 95% CI 1.01–5.52) and for the combined
cardiovascular outcome with all-cause deaths (HR
2.67, 95% CI 1.23–5.82) than case group participants
in the younger age group (33 years or younger),
whereas older control group participants (older than
33 years) were at significantly higher risk for cardio-
vascular deaths (HR 8.02, 95% CI 1.02– 63.01) and

VOL. 120, NO. 4, OCTOBER 2012 Gastrich et al Outcomes in Women With Preeclampsia or Eclampsia 827
 1.0

Product-limit survival probability

1.0
Product-limit survival probability

0.8 0.8

0.6 0.6

0.4 0.4

Case 0.2 Case

0.2
Control Control
Censored Censored
0.0 0.0
0 1,000 2,000 3,000 4,000 5,000 6,000 0 1,000 2,000 3,000 4,000 5,000
A Time (days) B Time (days)

1.0 1.0

Product-limit survival probability

Product-limit survival probability

0.8 0.8

0.6 0.6

0.4 0.4

Case Case
0.2 0.2
Control Control
Censored Censored
0.0 0.0
0 1,000 2,000 3,000 4,000 5,000 6,000 0 1,000 2,000 3,000 4,000 5,000
Time (days)
C Time (days) D
Fig. 2. Kaplan-Meier survival product limit estimates for the combined cardiovascular outcome by study group. A.
Kaplan-Meier survival estimates for the cumulative combined cardiovascular outcome for case 1 (n⫽57) and control 1
(n⫽155) group women in the myocardial infarction (MI) study group. P value is based on adjusted Cox regression model.
B. Kaplan-Meier survival estimates for the cumulative combined cardiovascular outcome for case 1 (n⫽132) and control 1
(n⫽379) group women in the stroke study group. P value is based on adjusted Cox regression model. C. Kaplan-Meier
survival estimates for the cumulative combined cardiovascular outcome for case 2 (n⫽23) and control 2 (n⫽67) group
women in the MI study group. P value is based on adjusted Cox regression. D. Kaplan-Meier survival estimates for the
cumulative combined cardiovascular outcome for case 2 (n⫽90) and control 2 (n⫽263) group women in the stroke study
group. P value is based on adjusted Cox regression model. NA, not applicable; model could not be fitted.
Gastrich. Outcomes in Women With Preeclampsia or Eclampsia. Obstet Gynecol 2012.

the combined cardiovascular outcome with cardio- compared with case group participants in the stroke
vascular deaths (HR 2.78, 95% CI 1.15– 6.74) com- study group.
pared with case group participants. Results of cardiovascular outcomes indicated that
In analysis 2, comparison of case group partici- for the MI group, there were no stroke admissions or
pants with preeclampsia or eclampsia and a first deaths in both case group participants and control
(pregnancy-related) MI and stroke on the same ad- group participants. None of the outcomes was signif-
mission with control group participants with pre- icantly different between the case group participants
eclampsia or eclampsia but without a pregnancy- and the control group participants after adjusting for
related MI and stroke on the same admission was covariates (Table 2). Figure 2C shows that there were
performed. Results of patient characteristics indicated no significant differences in the combined cardiovas-
a higher percentage of case group participants in the cular outcome-free survival among case group partic-
MI and stroke study groups were admitted from an ipants and control group participants. In the stroke
emergency department compared with control group study group, case group participants were at signifi-
participants (Table 1). A higher percentage of case cantly higher risk for all-cause death and the com-
group participants had a history of anemia in the MI bined cardiovascular outcome with all-cause deaths
study group compared with control group partici- compared with control group participants (for all-
pants, whereas a higher percentage of control group cause deaths: absolute risk in case group partici-
participants had a history of cardiac dysrhythmia pants⫽0.111, absolute risk in control group partici-

828 Gastrich et al Outcomes in Women With Preeclampsia or Eclampsia OBSTETRICS & GYNECOLOGY
pants⫽0.019, absolute risk difference⫽0.092, number
needed to treat⫽10.9; for the combined cardiovascu-
lar outcome with all cause deaths: absolute risk in case
group participants⫽0.111, absolute risk in control
group participants⫽0.027, absolute risk differ-
ence⫽0.084, number needed to treat⫽11.9). How-
ever, case group participants were not significantly
different from control group participants with respect
to the combined cardiovascular outcome with cardio-
vascular deaths (Fig. 2D).
Results of the analysis by age groups showed that
none of the outcomes was significantly different be-
tween the case group participants and the control
group participants for either the younger (34 years or
younger) or the older (older than 34 years) MI study
group. In the younger stroke study group (31 years or
younger), case group participants were at significantly
higher risk for all-cause death (HR 10.5, 95% CI 2.1–
53.0), the combined cardiovascular outcome with all-
cause deaths (HR 6.82, 95% CI 1.67–27.83), and the
combined cardiovascular outcome with cardiovascular
deaths (HR 14.04, 95% CI 1.53–129.34) compared with
control group participants. No significant differences in
the outcomes were observed between case group par-
ticipants and control group participants in the older age
group (older than 31 years).
DISCUSSION
A history of preeclampsia is a risk factor for coronary
artery disease, MI, and cardiovascular death.6,19 The
link between a higher risk of cardiovascular disease in
later life in women with preeclampsia (PE) was sug-
gested in a previous study20 that reported an increased
prevalence of previous preeclampsia or eclampsia in
women who had later experienced an MI.20 Our
study indicates that preeclampsia or eclampsia not
complicated by MI or stroke during that pregnancy
may not confer a very high risk for subsequent MI
and stroke in up to 16 years of follow-up. Regarding
stroke risk, our data suggest that other known risk
factors for stroke put women at greater risk for stroke
than preeclampsia or eclampsia complicated by a
stroke.
Studies examining long-term effects of preeclamp-
sia or eclampsia suggest more adverse cardiovascular
outcomes5,8 –10,12,14 that our study did not address. Tai-
wanese cohort studies of women using an index date 90
days before delivery8 resulted in a significantly higher
risk of stroke during pregnancy and in the first postpar-
tum year,8 as well as a significantly higher risk of major
adverse cardiovascular events (MI and stroke) during
pregnancy with continuing significant risk to more than
36 months postpartum.5 However, these studies did not
VOL. 120, NO. 4, OCTOBER 2012 Gastrich et al
compare women without preeclampsia or eclampsia
who had stroke.
The risks of cardiovascular sequelae in women
with preeclampsia or eclampsia cannot be dismissed.
The relationship and etiology of PE and cardiovascu-
lar disease are complex and characterized by several
markers, including endothelial dysfunction,12,21–24
metabolic abnormalities, oxidative stress, enhanced
inflammatory response, hypercoagulability,25 arterial
stiffness,23 and common molecular biomarkers.26 The
Stroke Prevention in Young Women study showed
that women who had a history of PE were 60% more
likely to have a remote nonpregnancy-related isch-
emic stroke than those without a history of PE.9
Pregnancy-related acute MI may convey significant
maternal morbidity and mortality in women.7 Our
study does not include women without preeclampsia
or eclampsia and without MI for comparison. In our
study, women with preeclampsia or eclampsia with an
index stroke were at significantly higher risk for
all-cause death and the combined cardiovascular out-
come (with all-cause death) compared with women
with preeclampsia or eclampsia without index stroke.
Limitations in our study include a lack of patient-
level data on typical cardiac-related risk factors (eg,
high cholesterol, medications, smoking, blood pres-
sure, and blood transfusions),27 and there was no
information pertaining to the trimester in which the
women in our study with preeclampsia or eclampsia
had diagnoses and delivered. Early PE (less than 34
weeks) appears to be more related to the development
of a markedly altered cardiovascular response (probably
initiated by a placental disorder factor), which has
implications for cardiovascular disease sequelae.25,28 –31
Our study design cannot generate incidence data,
and data were collected retrospectively.32 Case-con-
trol studies may prove an association, but they do not
demonstrate causation.32 We did not have data on the
control group participants (control 1) relating to their
pregnancy history.2 Another methodologic limitation
with this study is that we used only ICD-9 codes.
Because some of our preeclampsia or eclampsia case
group participants may have had preexisting hyper-
tension, we included only the diagnosis of preeclamp-
sia or eclampsia in the study.
The strengths of the study include the size of the
population studied and the 16-year time interval on
data from patients admitted to all nonfederal hospitals
in New Jersey. Our results confirm the supposition
that women with preeclampsia or eclampsia but with-
out index stroke have a lower risk of all-cause deaths
than women with preeclampsia or eclampsia with an
index stroke. The rates of subsequent MI and stroke
Outcomes in Women With Preeclampsia or Eclampsia 829
events were much lower in our case group partici-
pants and control group participants from analysis 1
than those observed for the general population in the
state (for MI: rate in case group participants 5.3% and
rate in control group participants 9.7%, compared
with general population 17.7%; for stroke: rate in case
group participants 3.8% and rate in control group
participants 11.6%, compared with rate in general
population⫽11.9%). This may be attributable to the
older age of patients in the general population expe-
riencing these conditions (median age for MI 69
years, median age for stroke 75 years).
A follow-up study is needed to compare control 2
group women with matched groups of normotensive
pregnant women in the general population whose
information is not presently in the Myocardial Infarc-
tion Data Acquisition System database. To better
understand the relationship between cardiovascular
events during pregnancy and later life cardiovascular
sequelae, clinicians should consider including a more
detailed preeclampsia or eclampsia history in all
previously pregnant women.29
In conclusion, one of the most important findings
of our study is that women with preeclampsia or
eclampsia but without an index stroke have lower risk
of cardiovascular outcomes than women with pre-
eclampsia or eclampsia with an index stroke. Women
with preeclampsia or eclampsia and an index MI and
stroke fare better than those with an MI and stroke
without preeclampsia or eclampsia. This finding may
be attributable to increased comorbidities in the con-
trol group. These data lend support to the designation
of preeclampsia as a risk factor for cardiovascular
disease in women by the American Heart Association
Effectiveness-Based Guidelines for the Prevention of
Cardiovascular Disease in Women—2011 Update.29
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Outcomes in Women With Preeclampsia or Eclampsia 831