Hypertension in Pregnancy: A CVD Red

Flag Not to Be Ignored

Authors: News Author: Marlene Busko; CME Author: Charles P. Vega, MD

CME / ABIM MOC / CE Released: 8/10/2018

Clinical Context
Preeclampsia affects 3% to 5% of pregnancies, and eclampsia develops in 0.05% to 0.93% of
pregnant women. The lifetime prevalence of hypertensive disorders of pregnancy (HDP) is
approximately 15%. Although hypertension usually resolves with delivery in most cases of
HDP, there can be sinister and severe long-term complications of these disorders. McDonald
and colleagues performed a systematic review and meta-analysis in the November 2008 issue
of the American Heart Journal to assess the cardiovascular risk associated with preeclampsia
and eclampsia.[1]

The researchers reviewed 5 case-control and 10 cohort studies. Overall, the risk for
subsequent cardiac disease was increased more than 2-fold in comparing women with a
history of preeclampsia/eclampsia with women without HDP, and more severe
preeclampsia/eclampsia was associated with a higher risk for cardiac disease. The respective
risk for cerebrovascular disease was elevated to a similar degree, whereas the odds ratio for
peripheral arterial disease among women with preeclampsia/eclampsia was elevated, but did
not reach statistical significance. The relative risk for cardiovascular mortality in comparing
women with preeclampsia/eclampsia vs no HDP was 2.29 (95% CI, 1.73 - 2.04).

Although there is a clear link between HDP and incident cardiovascular disease (CVD), the
effect of HDP on the development of important cardiovascular risk factors has not been well-
elucidated. The current study addresses that issue.

Study Synopsis and Perspective

New research shows that young women with gestational hypertension or preeclampsia in
their first pregnancy were twice as likely as other pregnant women to develop chronic
hypertension decades later.

They also had a 70% greater risk of developing type 2 diabetes and a 33% greater risk of
developing hypercholesterolemia, even after extensive adjustment for prepregnancy
confounders, such as body mass index, smoking, and family history.

This cohort of pregnant women had an average age of only 27 years, yet those who had new-
onset hypertension that resolved after pregnancy developed cardiovascular risk factors at a
younger age, lead author Jennifer J. Stuart, ScD, from Brigham and Women's Hospital and
Harvard Medical School, Boston, Massachusetts, stressed to theheart.org | Medscape
Cardiology.
These pregnancy complications are like a red flag, she said, signaling the need to start
screening for these risk factors at an earlier age.

"Women who experience preeclampsia or gestational hypertension should tell their doctor
and adopt a heart healthy diet and lifestyle, just like they would if they had a family history of
[CVD], to reduce cardiovascular risk and delay disease onset," she said in a statement[2]
regarding the study, which was published online July 3 in the Annals of Internal Medicine.[3]

Abigail Fraser, PhD, MPH, from Bristol Medical School, University of Bristol, United
Kingdom, who wrote an accompanying editorial,[4] agreed in an email to theheart.org |
Medscape Cardiology.

"Current US and European guidelines already recognize that women with [HDP] are at
increased risk of CVD, and that a woman's obstetric history is relevant to how women are
monitored in the years after pregnancy," she explained, "but the guidelines cannot
recommend exactly when and what should be monitored because the evidence simply isn't
there," Dr Fraser said.

"This is where the study by Stuart et al makes a novel contribution," she said, "by showing
that women with [HDP] are diagnosed with hypertension, diabetes, and hypercholesterolemia
at an earlier age, thus suggesting that if they were monitored more intensely and at an earlier
age, these risk factors could be detected and treated in a timely manner."

Which Risk Factors? When to Screen?

Although not the first study to suggest a link between gestational hypertension and
subsequent CVD, this study includes the most thorough adjustment for prepregnancy
confounders of this relationship and is 1 of the largest studies with 1 of the longest follow-
ups, Dr Stuart and colleagues note.

Approximately 15% of pregnant women develop a hypertensive disorder during pregnancy,

which research suggests almost doubles their risk of developing subsequent CVD, they
explain.

In fact, the 2011 American Heart Association guidelines recommend that clinicians evaluate
CVD risk by screening for a history of hypertensive disorders of pregnancy, but "few data
exist on which risk factors should be screened for as well as the frequency and timing of
screening," the study authors note.

For the study, Dr Stuart and colleagues identified 58,671 pregnant women in the Nurses'
Health Study II who did not have hypertension, type 2 diabetes, or hypercholesterolemia at
baseline.

Of these women, 2.9% developed gestational hypertension (new-onset blood pressure of at

least 140/90 mm Hg), 6.3% developed preeclampsia (gestational diabetes plus proteinuria),
and the rest were normotensive during their first pregnancy. The births occurred between
1964 and 2008.
By the end of 2013 (up to 50 years of follow-up), a third of the women had developed
chronic hypertension, 6.4% had developed type 2 diabetes, and 55.6% had developed
hypercholesterolemia.

Compared with a normotensive pregnancy, having a hypertensive disorder in pregnancy

predicted an increased risk of developing a CVD risk factor, after adjustment for body mass
index, physical activity, family history of hypertension or type 2 diabetes, age at first birth,
age in 1989, race/ethnicity, oral contraceptive use, smoking, alcohol consumption,
Alternative Healthy Eating Index score, and parental education.

Table. Adjusted Risk of Developing CVD Risk Factor

Gestational Hypertension Preeclampsia

CVD Risk Factor
HR (95% CI) HR (95% CI)
Chronic hypertension 2.79 (2.61-2.97) 2.21 (2.10-2.32)
Type 2 diabetes 1.65 (1.42-1.91) 1.75 (1.58-1.93)
Hypercholesterolemia 1.36 (1.28-1.45) 1.31 (1.25-1.36)
After full adjustment compared with normal blood pressure in pregnancy. CI, confidence
interval; HR, hazard ratio.

An Opportunity to Reduce CVD

Women who developed chronic hypertension were diagnosed at a median age of about 45
years (range, 40-50 years) if they had gestational diabetes or preeclampsia vs a median age of
50 years (range, 45-54 years) if they had normal blood pressure during their pregnancy.

The increased risk of developing chronic hypertension was strongest in the 5 years after they
gave birth, but continued throughout the follow-up.

Similarly, women who developed type 2 diabetes or hypercholesterolemia did so at a younger

age if they had hypertensive disorders in pregnancy.

"It is not yet clear whether HDP unmasks preexisting cardiovascular risk through the 'stress
test' of pregnancy or whether it induces endothelial or organ damage that alters a woman's
trajectory toward development of CVD risk factors," Dr Stuart and colleagues write.

In any case, these women may benefit from lifestyle interventions and screening to reduce
their risk and delay disease onset.

Moreover, they add, "just as guidelines exist to screen for [type 2 diabetes] among women
with a history of gestational diabetes, our findings may inform similar guidelines on
screening for CVD risk factors among women with a history of HDP."
We need more prospective studies with repeated measures of CVD risk factors in postpartum
women to determine the optimal monitoring and prevention strategies, according to Dr
Fraser.

"Pregnancy may...provide an opportunity to identify CVD, intervene, and ultimately reduce

the disease burden in women," she writes.

The research was funded by the National Institutes of Health. Dr Stuart and Dr Fraser have
no relevant financial disclosures.

Ann Intern Med. Published online July 3, 2018.

Study Highlights
 Researchers used data from the Nurses' Health Study II to address their study
question. This cohort of 116,429 female US registered nurses between the ages of 25
and 42 years enrolled in the study in 1989.
 Women whose first delivery occurred before age 18 years or after age 45 years were
excluded from analysis, and women with preexisting diabetes, hypertension,
hypercholesterolemia, or cardiovascular disease before pregnancy were also excluded.
 HDP were reported retrospectively by participants. A review of a selection of medical
records confirmed that the majority of these reports were accurate.
 Incident hypertension, diabetes, and hypercholesterolemia was also determined by
participant self-report, and these reports were also found to be accurate in comparison
with select medical records.
 The main study outcome was the relationship between HDP and the risks for incident
hypertension, diabetes, and hypercholesterolemia. These results were adjusted to
account for demographic factors, family history, prepregnancy body mass index,
health habits, and oral contraceptive use.
 First newborn deliveries occurred among the study cohort at an average age of 26.8
years; 2.9% of women had gestational hypertension, and 6.3% developed
preeclampsia. Demographic and lifestyle data were generally similar in the HDP and
normotensive groups.
 Overall, at the end of follow-up in 2013, 33.3% of participants had chronic
hypertension. 6.4% had developed type 2 diabetes, and 55.6% had
hypercholesterolemia.
 HDP were associated with higher risks for incident hypertension (HR, 2.8; 95% CI,
2.6-3.0) and type 2 diabetes (HR, 1.7; 95% CI, 1.4-1.9). HDP were also associated
with a higher risk for hypercholesterolemia (HR, 1.3; 95% CI, 1.3-1.4).
 HDP were associated with the development of these cardiovascular risk factors at
younger ages compared with normal blood pressure during pregnancy.
 The HRs for cardiovascular risk factors associated with HDP were highest in the first
5 years after childbirth.
 The risk for diabetes associated with HDP only became significant more than 20 years
after childbirth, whereas the risk for hypercholesterolemia was more immediate and
stable over time.
 HDP in more than 1 pregnancy were associated with higher rates of incident
cardiovascular risk factors compared with HDP in 1 pregnancy alone.
Clinical Implications
 A previous meta-analysis found that preeclampsia/eclampsia was associated with
higher risks for incident cardiac and cerebrovascular disease, as well as a higher risk
for cardiovascular death.
 The current study by Getahun and colleagues suggests that HDP are associated with
higher risks for incident hypertension, diabetes, and hypercholesterolemia.
 Implications for the Healthcare Team: The presence of HDP should prompt the
healthcare team to perform required screening for hypertension and
hypercholesterolemia, and women with a history of HDP should be considered at
higher risk for type 2 diabetes as well.