Hypertension in Pregnancy: A CVD Red Flag Not to Be Ignored

New research shows that young women with gestational hypertension or pre-eclampsia 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 cardiovascular disease–to reduce cardiovascular risk and delay disease onset," she said in a statement regarding the study, which was published July 3 in Annals of Internal Medicine.

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

"Current US and European guidelines already recognize that women with hypertensive disorders of pregnancy (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," 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 cardiovascular disease (CVD), this one includes the most thorough adjustment for prepregnancy confounders of this relationship and is one of the largest studies with one of the longest follow-ups, 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, 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^a

CVD Risk Factor	HR (95% CI)
CVD Risk Factor	Gestational Hypertension	Pre-eclampsia
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)
^aAfter full adjustment compared with normal blood pressure in pregnancy. HR = hazard ratio.

An Opportunity to Reduce CVD

Women who developed chronic hypertension were diagnosed at a median age of about 45 (range, 40 - 50) years if they had gestational diabetes or pre-eclampsia vs a median age of 50 (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 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," Stuart and her 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 hypertensive disorders of pregnancy.

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 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. Stuart and Fraser have no relevant financial disclosures.

Ann Intern Med. Published July 3, 2018. Abstract, Editorial

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