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First-Ever Women-Specific Guidelines Warn of Long-Term Stroke Risks from Pregnancy-Related Complications

Rukovets, Olga

doi: 10.1097/01.NT.0000445552.66221.42
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The American Heart Association/American Stroke Association released the first-ever women-specific guidelines on reducing stroke risk, which recommended creating a female-specific score to reflect stroke risk across the lifespan.

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Although men and women do share many of the same high-risk predictors for stroke — such as smoking, family history, and physical inactivity — some risk factors are either exclusive to women or affect women disproportionately. With this in mind, the American Heart Association/American Stroke Association convened a panel of experts in neurology, obstetrics, cardiology, epidemiology, and internal medicine to review and assess the literature on stroke risk in adults through May 15, 2013. They published the first gender-specific guidelines for stroke prevention in women — which were endorsed by the AAN, the American Association of Neurological Surgeons, and the Congress of Neurological Surgeons — in the Feb. 6 online edition of Stroke.

“This endeavor is important because women differ from men in a multitude of ways, including genetic differences in immunity, coagulation, hormonal factors, reproductive factors including pregnancy and childbirth, and social factors, all of which can influence risk for stroke and impact stroke outcomes,” the guideline authors wrote.

Overall, our extensive review of the evidence pointed to more gaps in knowledge than definitive recommendations, the lead author Cheryl Bushnell, MD, an associate professor of neurology, and director of the Wake Forest Baptist Stroke Center in Winston-Salem, NC, told Neurology Today. The primary message from the guidelines “is that many of the unique risk factors for women are present at younger ages (due to oral contraceptive use, pregnancy complications), so recognition of stroke risk and prevention strategies could start early to keep women from having a preventable stroke,” she said.

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The most important recommendation from our review, Dr. Bushnell said, “is that women with a history of hypertension or preeclampsia during pregnancy are at risk for stroke and hypertension later in life.” Before this guideline, some providers and few women knew about this risk, she explained, and “the evidence for this relationship is pretty solid, as multiple meta-analyses have come to the same conclusion.” For this reason, the guidelines recommend documenting hypertension in women during pregnancy, preeclampsia/eclampsia, or gestational diabetes as risk factors for stroke in the medical record, “and beginning strategies to decrease their future risk of stroke at early ages, even as early as during their childbearing years.”

“We suggest considering treating blood pressure in the moderate range (150-159 mmHg systolic) for pregnant women, although there has to be careful consideration of maternal and fetal risk and benefit in this group” because of medication side effects. Predicting which women may go on to develop severe hypertension during pregnancy (>160/110 mmHg), she added, might also help identify which women should be treated.

The guidelines also make a strong recommendation for treating women at high risk of preeclampsia with low-dose aspirin or calcium supplements. “The implication is that if you can prevent preeclampsia, perhaps you have reduced the future risk of stroke by at least one notch,” said Dr. Bushnell.

The guidelines may be useful for neurologists who are counseling female patients with migraine with aura on how to reduce their overall stroke risk by focusing on some of the factors unique to or more common in women. Many migraine medications may also lower blood pressure, she said, thus, reducing stroke risk and “killing two birds with one stone.”

The authors recommended the development of a female-specific risk score to reflect stroke risk across the lifespan. This would help clinicians “determine a woman's long term-risk in the future, and be used as a guide to developing early prevention strategies and determine how early they should start,” said Dr. Bushnell. Potentially, these differences in risk score may point to gender-specific dosing or pharmacological approaches, “but there is a huge gap in research in this area,” she said, adding that recognizing these risk factors is the first step. [See sidebar “Guideline Recommendations for Reducing Stroke Risk in Women” for additional recommendations.]

Dr. Bushnell noted that further research is also needed to determine if these gender-specific risk factors are independently related to future stroke risk when traditional risk factors, such as cholesterol and hypertension, are included in the score. Studies are needed, she said, to determine which women with hypertension during pregnancy or preeclampsia will be at highest risk for stroke later in life, as well as among “diverse populations, since African Americans, in particular, are at risk for hypertension during pregnancy.”

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The take-home message here is that there are different risk factor patterns in women, and “that pregnancy, preeclampsia, distribution of migraines, atrial fibrillation, diabetes, and hypertension are important differences that should be known by generalists and by people evaluating risk profiles in patients,” said Joshua Z. Willey, MD, an assistant professor in the Stroke Division at Columbia University College of Physicians and Surgeons in New York City and assistant attending neurologist on the Stroke Service at New York Presbyterian Hospital, who was not involved with the guidelines.

Women often don't consider themselves at high-risk for cardiovascular disease and stroke, Dr. Willey said, so this is an especially important guideline for public awareness, as well as for any clinicians who may not be as familiar with the literature about gender-specific stroke risk factors.

Tobias Kurth, MD, director of research at Inserm Research Center for Epidemiology and Biostatistics and the University of Bordeaux in France, agreed, adding that “there was a time when we believed that women were protected from cardiovascular disease because of their hormonal status. Now, since we are all living longer, we know the risk picks up exponentially later in life for women.” We also know that many strokes occur in midlife for women, he added, and strokes in women tend to be more disabling.

An important point made in these guidelines, Dr. Willey said, is the way that traditional risk factors interact or affect women more than men — particularly atrial fibrillation. He noted that the commonly used CHADS2 stroke prediction score for patients with atrial fibrillation does not include gender as a part of the calculation, though the revised CHA2DS2-VASc score does. [See sidebar “Tools for Predicting Stroke Risk in Patients with Atrial Fibrillation” for a comparison of the CHADS2 and CHADS2DS2-VASc scores.] This guideline makes a “very strong case that, particularly as women get older and as they become a larger segment of the population because they tend to outlive men, atrial fibrillation takes on added importance as a risk factor for stroke in women.”

From his own clinical experience, Dr. Willey said, many female patients don't seem to be aware of risk factors like gestational diabetes or other pregnancy-related complications like preeclampsia. Thus, these guidelines may help encourage important conversations with patients which help identify any heightened risk of hypertension or risk factors for stroke.

The authors' goal of creating a gender-specific stroke risk score is likely a good one, said Dr. Kurth, but it will require much more detailed data on the differences in stroke risk among genders. “Given the fact that the risk factor pattern is so different between men and women, having a complete, independent risk score for each gender will allow us to better classify risk groups and to offer better preventive strategies to reduce the risk, which is the ultimate aim.”

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We need to validate these differences in large cohort studies “to see if there are differences by gender beyond what they've outlined already in these guidelines,” Dr. Willey said.

In addition, he said, research on the impact of stroke on independence and recovery is critical, since stroke occurs at later ages and has greater severity in women. “We need to understand not just risk factors and incidence, but also recovery from stroke in women and the long-term functional impairment,” said Dr. Willey.

We also don't know for sure yet whether treating all these risk factors makes a difference, said Dr. Kurth. For example, for migraine with aura, “we have consistent evidence that there is increased risk for stroke, but we don't understand why and what can be done. Also for some of the risk factors during pregnancy — are these due only to hormonal changes? Or are other changes important? Is it just during pregnancy or also for a longer time after birth where women are at increased risk?” We need solutions and prevention strategies for women, he said, and “I think that's certainly something that the authors are very aware of, and they are calling directly or indirectly to solve these problems.”

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The guidelines outline stroke risks unique to women and provide scientifically-based recommendations on how best to treat them, including:

* Women with a history of high blood pressure before pregnancy should be considered for low-dose aspirin and/or calcium supplement therapy to lower preeclampsia risks.

* Women who have preeclampsia have twice the risk of stroke and a four-fold risk of high blood pressure later in life. Therefore, preeclampsia should be recognized as a risk factor well after pregnancy, and other risk factors such as smoking, high cholesterol, and obesity in these women should be treated early.

* Pregnant women with moderately high blood pressure (150-159 mmHg/100-109 mmHg) may be considered for blood pressure medication, whereas expectant mothers with severe high blood pressure (160/110 mmHg or above) should be treated.

* Women should be screened for high blood pressure before taking birth control pills because the combination raises stroke risks.

* Women who have migraine headaches with aura should stop smoking to avoid higher stroke risks.

* Women over age 75 should be screened for atrial fibrillation risks due to its link to higher stroke risk.

Source: American Heart Association/American Stroke Association Scientific Statement:

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•. Bushnell C, McCullough LD, Awad IA, et al., on behalf of the American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Council for High Blood Pressure Research. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014. E-pub 2014: Feb. 6.
•. AAN evidence-based guidelines for stroke:
© 2014 American Academy of Neurology