Professional Documents
Culture Documents
CONTENTS
Cardiovascular disease in
women: magnitude of
the problem
Recognized cardiovascular
risk markers in women
Is preeclampsia a new,
novel cardiovascular
risk factor?
What should clinicians do?
Conclusions
Expert commentary
Key issues
Pregnancy is a metabolic and vascular stress test for women and those who fail are at
increased risk of long-term cardiovascular complications. Specifically, women who
develop preeclampsia (and/or other manifestations of placental dysfunction) are at
increased risk of coronary heart disease, stroke and cardiovascular disease in general.
The risk is highest among women who develop both maternal (e.g., hypertension and
proteinuria) and fetal (e.g., intrauterine growth restriction) manifestations of abnormal
placentation, especially with preterm delivery. Most women who develop a maternal
placental syndrome return to a normal clinical state in the weeks following pregnancy and
their absolute risk of cardiovascular disease in the short term is very low. However, perhaps
having a placentally complicated pregnancy affords women the opportunity to
personalize risk and take action. Action is needed. The fact that we, as a population, are
getting heavier and more sedentary is an urgent public health issue. The American Heart
Association recommends that all women (even those at low cardiovascular risk) pursue
dietary and lifestyle changes, in addition to smoking cessation. Engaging women of childbearing age who may be motivated by a complicated pregnancy would be very
valuable, from a public health perspective, given the prevalence and importance of
cardiovascular disease in women, and the central role of the woman as caregiver to
children, spouses and other family members.
Expert Rev. Cardiovasc. Ther. 5(2), 283294 (2007)
Five-year view
References
Affiliations
www.future-drugs.com
10.1586/14779072.5.2.283
ISSN 1477-9072
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286
Table 1. Retrospective cohort studies linking abnormal placentation with cardiovascular disease .
Study
Study participants
Median
follow-up
(year)
MPS at baseline
Future CV risk
Adjusted RR
[95% CI]
Mann et al.
(1976)
Preeclampsia (requiring
drug treatment
or hospitalization)
Myocardial
infarction
2.8 [-,-];
p < 0.05
[34]
Jonsdottir
et al. (1995)
41.9
Any hypertension
in pregnancy
Death from
ischemic
heart disease
1.5 [1.1,2.0]
[26]
Preeclampsia
Death from
ischemic
heart disease
1.9 [1.0,3.5]
Eclampsia
Death from
ischemic
heart disease
2.6 [1.1,6.1]
Ref.
Hannaford
et al. (1997)
Toxemia
Any ischemic
heart disease
1.7 [1.3,2.2]
[24]
Smith et al.
(2001)
Preeclampsia
Ischemic
heart disease
2.0 [1.5,2.5]
[30]
Preeclampsia + SGA
+ preterm delivery*
Ischemic
heart disease
7.0 [3.0,14.5]
Preeclampsia
CV death
1.6 [1.0,2.7]
Preeclampsia +
preterm delivery
CV death
8.1 [4.3,15.3]
Gestational hypertension
Cerebrovascular
death
1.5 [0.7,3.3]
Preeclampsia
Cerebrovascular
death
2.1 [1.0,4.3]
Gestational hypertension
CV disease
2.8 [1.6,4.8]
Mild preeclampsia
CV disease
2.2 [1.3,3.6]
Severe preeclampsia
CV disease
3.3 [1.7,6.5]
Low infant BW
Major stroke
1.3 [1.0,1.6]
Preterm delivery*
Major stroke
1.9 [1.4,2.7]
Low infant BW +
preterm delivery
Major stroke
2.7 [1.4,5.1]
Irgens et al.
(2001)
Wilson et al.
(2003)
Kestenbaum
et al. (2003)
Pell et al.
(2004)
15-19
13
15-19
7.8
[25]
[33]
[27]
[28]
Smith et al.
(2005)
20.4
Low BW
CV death
1.3 [1.2,1.4]
[31]
Ray et al.
(2005)
8.7
MPS composite
Premature
CV disease
2.0 [1.7,2.2]
[29]
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287
Table 1. Retrospective cohort studies linking abnormal placentation with cardiovascular disease (cont.).
Study
Study participants
Median
follow-up
(year)
MPS at baseline
Future CV risk
Adjusted RR
[95% CI]
MPS composite +
poor fetal growth
Premature
CV disease
3.1 [2.2,4.5]
Premature
CV disease
4.4 [2.4,7.9]
Ref.
Funai et al.
(2005)
24.5-36.5
Preeclampsia
3.1 [2.1,4.3]
[23]
Wikstrom
et al. (2005)
403,550 primips
15
Any HDP
1.7 [1.5,2.0]
[32]
Gestational hypertension
2.0 [1.7-2.5]
1.6 [1.3-2.0]
Mild preeclampsia
2.1 [1.8-2.5]
1.9 [1.6-2.2]
Severe preeclampsia
3.1 [2.4-4.1]
2.8 [2.2-3.7]
2.6 [1.8,4.7]
Arnadottir
et al. (2005)
50 for cases
55 for
controls
Any HDP
[22]
Mild/moderate
preeclampsia
Severe preeclampsia
Eclampsia
Reproduced with permission from [29].
*Preterm delivery is defined as delivery before 37 weeks gestation.
Prevention requires both recognition of the problem and adoption of strategies to decrease risk. Physician awareness of womens
cardiovascular risk is inadequate, according to a national survey
of American physicians (primary care, obstetricians and cardiologists). These physicians were more likely to underestimate the
cardiovascular risk of women in an intermediate risk category,
compared with men of the same risk [38]. It is likely that women
themselves must be targeted in educational initiatives.
Personalization of cardiovascular risk
There are inconsistencies and questionable assumptions in the testing of this theory. These include the assumption that
100
intrauterine growth restriction (which
has many causes) is due to poor nutrition
99
and an inability to adequately account for
Unaffected pregnancy
the impact of smoking and social class.
MPS
MPS and poor fetal growth
However, there is tremendous support for
98
MPS and fetal death
this theory and this may motivate women
to act altruistically to provide a healthy
97
lifestyle for their child.
Consequently, we may have a window of
opportunity for the identification of
96
women (and children) at risk following a
pregnancy complicated by gestational
95
hypertension, preeclampsia and/or another
component of the maternal placental syndrome. Identification of such individuals
0
at an early stage (before complications have
4
0
1
2
3
5
6
7
8
9
10 11 12 13 14
occurred) has been a major barrier to risk
Times since index delivery (years)
reduction [14].
It is well established that GDM is assoFigure 3. Risk of premature cardiovascular disease associated with abnormal placentation.
ciated with an increased risk (approxi- MPS: Maternal placental syndrome.
mately 30%) of Type II diabetes in the Adapted from [29].
long term [40,41]. It is well accepted that
these women should be counseled about this risk, the need to Strategies to decrease cardiovascular risk
monitor serum glucose at regular intervals postpartum and the There are a number of theoretical options for CVD prevention
benefits of modifying lifestyle [14]. Presumably, if there is per- in women with a history of adverse placental outcome: ensure
sonalization of risk and women are to effect change in their compliance with existing recommendations for traditional
behaviors, then the information that they receive should affect cardiovascular risk marker screening and/or treatment, as they
their long-term health perception. This was confirmed in a apply to all women of childbearing age; consider early screening
prospective cohort of 106 women with GDM, who received for traditional cardiovascular risk markers (and/or their treatthe appropriate information in a specialty clinic and were fol- ment); and/or consider early treatment of modifiable cardiolowed up 35 years after pregnancy by postal survey [42]. vascular risk markers. These will be addressed consecutively but
Compared with normal pregnancy controls (and corrected for they are not mutually exclusive. For example, the first and third
factors independently related to health perception), women approaches may be undertaken in conjunction.
with GDM were more worried about their own health, rated
their children as less healthy and perceived themselves as more Screening
likely to have diabetes. The study did not examine whether In 2004, the American Heart Association published evidencethe change in health perception was associated with a change based clinical guidelines for CVD prevention in women [2].
in health behaviors.
These guidelines recommended treatment of individual risk
In summary, women change their lifestyle for themselves markers (e.g., hyperlipidemia). When should screening for
and for their family. Having a history of a maternal placental these risk markers begin in the otherwise healthy postpartum
syndrome may be a way to emphasize or personalize risk, even woman with a history of a maternal placental syndrome?
if that risk is already apparent (e.g., owing to a history of
In Canada, the evidence-based periodic health examination
pre-existing hypertension, obesity or diabetes mellitus). for women aged 2164 years suggests routine screening only
Womens health perceptions can be changed through coun- for tobacco use and hypertension, in the absence of other
seling related to pregnancy complications, using GDM as an cardiovascular risk markers (TABLE 2).
example. Through an altered perception of personal risk,
If one looks to other sources of information for screening recwomen with a history of preeclampsia or another placental ommendations, consensus guidelines are available that are not
syndrome may be more receptive (than other women of child- graded based on available evidence. The Canadian Diabetes
bearing age) to cardiovascular risk-reduction strategies, for Association recommends screening for diabetes (by fasting
themselves and for their families. What are the options for plasma glucose) at age 40 years and then every 3 years thereafintervention once increased risk has been identified and, ter in the absence of cardiovascular risk markers [102]. The
hopefully, personalized?
American Diabetes Association is similar in recommending
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289
Table 2. Recommendations of the Canadian Task Force on the Periodic Health Exam: cardiovascular risk
factor screening*.
Risk marker
Minimal approach
Smoking
Blood pressure
Case-finding should be considered in all persons aged 2164 years, because of high prevalence, effective detection
manoevre and efficacious treatment (III, B)
Not recommended for asymptomatic and nonpregnant population without other cardiovascular risk markers
(II-2, D). Otherwise, screening should be individualized
Lipids
Not clear whether or not this should be performed for women of child-bearing age (III, C)
Obesity
With obesity-related disease, weight reduction can alleviate symptoms and reduce the need for drug therapy for
related diseases (I, B). Insufficient evidence to recommend against weight-reduction therapy in obese adults without
obesity-related disease owing to the limited long-term effectiveness of weight reduction methods (I, C)
*The following levels refer to the type of studies on which the recommendation is based: I (at least one properly randomized controlled trial) II-2 (well-designed cohort or
casecontrol analytic studies, preferably from more than one center or research group) III (opinions of respected authorities, based on clinical experience, descriptive
studies or reports of expert committees). The following levels refer to the quality of the evidence on which to base the recommended clinical action: A (good), B (fair),
C (conflicting).
Diabetes mellitus, hypertension, hyperlipidemia, obstructive sleep apnea or coronary artery disease.
hypercholesteremia, would be a step-up from existing suggestions, as most of these women will be under 4050 years of age.
There is currently no evidence to advocate this approach and the
cost implications are unknown. One could argue against early
screening and more aggressive intervention based on the fact that
women with a history of a maternal placental syndrome have a
10-year cardiovascular risk that still appears to be low (<10%).
Treatment
Table 3. American Heart Association lifestyle recommendations for cardiovascular disease prevention in all women.
Intervention
Smoking
cessation
Heart:
healthy diet
To adopt an overall healthy eating pattern that includes intake of a variety of fruits, vegetables, grains, low-fat or nonfat
diary projects, fish, legumes and sources of protein low in saturated fat (e.g., poultry, lean meats, plant sources). Limit
saturated fat intake to <10% and calories, limit cholesterol intake to <300 mg/day and limit intake of trans fatty acids (I, B)
Physical activity To accumulate 30 min of moderate-intensity physical activity (e.g., brisk walking) on most, and preferably all, days of the
week (I, B)
Weight
reduction
To maintain/reduce their weight through an appropriate balance of physical activity, caloric intake and formal behavioral
programmes when indicated to achieve a body mass index of 18.5-24.9 kg/m2 and a waist circumference <78.4 cm (I, B)
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risk would presumably benefit less and, therefore, the cost would
be greater. Taking the societal perspective, compared with not
undertaking a lifestyle change program, implementing the plan
undertaken in the Diabetes Prevention Program study [47] for
high-risk individuals would cost US$62,600 per quality-adjusted
life-year (QALY). The program would be cost-saving over
30 years if the annual cost of the intervention could be reduced to
approximately US$100. This would be difficult indeed.
Special note: weight gain in pregnancy
Obesity is a risk marker for both the maternal placental syndrome and CVD so it will be present in many women with a history of preeclampsia or the maternal placental syndrome. Treatment of obesity is modestly effective (e.g., a loss of 35 kg for
1 year or more) [49]. The public-health focus has moved to prevention. As pregnancy-related weight gain is a trigger for weight
retention, it follows that weight during pregnancy warrants
special consideration.
Weight gain during a healthy pregnancy is unavoidable and
expected. The average weight gain is 12.5 kg. The recommended weight gain for women with a normal prepregnancy
BMI (19.926.6 kg/m2) is 1116 kg. Weight-gain goals are
lower for women who are overweight at the start of pregnancy.
The Stockholm Pregnancy and Weight Development Study
was a long-term follow-up study of women who had a mean
weight increase of 14.1 4.1 kg during pregnancy, 15 years
previously [50]. A number of important findings were made.
First, based on prepregnancy characteristics, it was difficult to
predict who was likely to retain pregnancy-related weight gain
after pregnancy. Not surprisingly, women who were overweight
on follow-up at 15 years had a higher prepregnancy BMI
(22.3 1.5 vs 20.5 1.6 kg/m2), gained more weight during
pregnancy (15.4 4.4 vs 13.6 3.7 kg), retained more weight
at 1 year postpartum and had more rapid age-related weight
gain between 1 and 15 years postpartum. However, most
women who became overweight had a normal prepregnancy
BMI of 2025 kg/m2. Also, the differences in prepregnancy
weight between women who became overweight (versus those
291
who did not) were small and variation was wide. Women who
became overweight were more likely to quit smoking during
pregnancy and less likely to breastfeed; otherwise, there were no
other demographics or pregnancy characteristics that differed
between groups. Previous reports on this cohort at 1 year postpartum identified an association between weight retention at
1 year postpartum and both less frequent exercise and a change
to more irregular eating habits. The overall conclusion was that
it is difficult to predict who will gain weight during pregnancy
and who will retain weight postpartum, and that there is much
that we do not know. Dietary and lifestyle changes associated
with having a new baby may play a role. At this stage, observation over time, rather than prevention by identifying those at
risk, appears to be the best option. Perhaps close follow-up of
women who are indeed gaining and retaining weight is the key
to halting and reversing this worrisome trend in their health.
In summary, in nonpregnant populations, dietary and lifestyle
changes are effective in decreasing surrogate markers of CVD
(e.g., glucose tolerance and BP), as well as cardiovascular outcomes per se. However, how best to make these dietary and lifestyle changes, and maintain those changes at a reasonable cost to
the public healthcare system is uncertain. These interventions
require time and effort on behalf of the patients and caregivers,
including those providing routine gynecological care.
Conclusions
At present, a history of preeclampsia, or another of the placentally mediated adverse pregnancy outcomes, can be regarded as
a novel cardiovascular risk factor. There are no existing guidelines or strategies in place for how to deal with this problem.
CVD is the number one killer of women. We must find ways,
through postpartum counseling and routine gynecological care,
to engage this section of the population and to ensure better
uptake of the general recommendation for all women to pursue
a healthy diet and lifestyle.
Five-year view
Key issues
Cardiovascular disease (CVD) is a womens health issue.
Pregnancy appears to be a metabolic and vascular stress test for women and those who fail are at increased risk of long-term
cardiovascular complications.
Women who develop preeclampsia (and/or other manifestations of a maternal placental syndrome) are at an increased risk of
coronary heart disease, stroke and CVD in the long term, although the absolute risk is low and not immediate.
The long-term risk of CVD is highest among women who develop both maternal (e.g., hypertension and proteinuria) and fetal
(e.g., intrauterine growth restriction) manifestations of abnormal placentation, especially with preterm delivery.
Most women who develop a maternal placental syndrome return to a normal clinical state in the weeks following pregnancy and
their absolute risk of CVD in the short term is very low.
Among women with a history of preeclampsia (or another maternal placental syndrome), it is unclear how this increased long-term
cardiovascular risk should be handled with respect to cardiovascular risk marker screening and/or treatment.
The American Heart Association recommends that all women (even those at low cardiovascular risk) pursue dietary and lifestyle
changes, in addition to smoking cessation.
Personalization of risk is an important component of engagement in risk reduction strategies.
292
as a caregiver to children, their spouse and other family members. Lifestyle interventions, which are useful for all women,
may improve subsequent pregnancy outcomes, as well as
References
Papers of special note have been highlighted as:
of interest
of considerable interest
1
11
12
26
15
27
28
29
16
18
10
www.future-drugs.com
14
17
24
25
23
Redman CWG. The placenta, preeclampsia and chronic villitis. In: The
Human Placenta. Redman CWG,
Sargent ILSP (Eds). Blackwell Scientific,
Oxford, UK, 433467 (1993).
286292 (2005).
13
19
20
21
22
30
31
32
33
293
34
35
36
37
38
39
40
41
294
42
43
Feig DS, Chen E, Naylor CD. Selfperceived health status of women three to
five years after the diagnosis of gestational
diabetes: a survey of cases and matched
controls. Am. J. Obstet. Gynecol. 178(2),
386393 (1998).
Genest J, Frohlich J, Fodor G,
McPherson R. Recommendations for the
management of dyslipidemia and the
prevention of cardiovascular disease:
summary of the 2003 update. CMAJ
169(9), 921924 (2003).
44
45
46
47
48
49
50
Websites
101
102
103
Affiliations
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.