A call for increased awareness of the high stroke burden in women

Current estimates suggest that 6.8 million Americans are living after having had a stroke, approximately 3.8 million of whom are women. Stroke is also the third leading cause of death among women. Although much of the difference in stroke prevalence and burden is because women, on average, live longer than men, some of it is related to factors unique to or more common in women.

It is these factors, which include hormonal exposures and pregnancy-related risks, that prompted the American Heart Association and American Stroke Association to create and publish guidelines in February that focus strictly on stroke prevention in women.

“How our society adapts to the anticipated increase in stroke prevalence in women is vitally important. Now more than ever, it is critical to identify women at higher risk for stroke and initiate the appropriate prevention strategies,” Cheryl Bushnell, MD, MHS, FACC, chair of the guideline writing group, and colleagues wrote in the statement.

It is important to emphasize stroke in women across the lifespan and to raise awareness about the unique risks of women compared with men, Bushnell told Cardiology Today. “These include pregnancy complications, such as preeclampsia, hormonal contraception and hormone therapy for menopausal symptoms. We also emphasize that there are risk factors that are more common in women than in men, such as migraines with aura, hypertension and atrial fibrillation.”

Stroke risk, prevention in women

Despite the prevalence of stroke in women, this is the first guideline dedicated to stroke risk and prevention in women issued by the AHA and ASA. According to the authors, the document covers topics specific to women in more detail than has been included in current primary and secondary stroke-prevention guidelines. It also provides more emphasis on stroke-specific issues in women than have been included in the current heart disease-prevention guideline for women.

There are two recommendations that are different from current practice and other guidelines, Bushnell said.

One recommendation is that treatment of pregnant women with systolic BP in the 150-mm Hg to 160-mm Hg range should be considered, once the risk and benefits to both the mother and fetus are considered. “Although potential fetal exposure of any medication needs to be carefully considered, many are relatively safe in pregnancy,” she said. “The idea is to prevent escalation of BP to dangerous levels, as strokes can occur with [systolic] BPs ≤160 mm Hg, and the long-term consequence of pregnancy-induced hypertension may be significant.”

The other new recommendation is to include hypertensive disorders during pregnancy as documented risk factors for CVD and stroke to jump start the prevention process earlier in women. “The data are clear that these pregnancy complications are an early sign of vascular disease because there is an association with a fourfold risk for developing hypertension and a twofold increased risk for stroke later in life,” Bushnell said.

“Whether these changes affect practice will depend on the buy-in from the obstetrical community because they are often in the role of primary care for women right after childbearing. In addition, we hope that women will take note of these messages and tell their doctors about their pregnancy history, since women often have primary care in a setting other than where they may have delivered their children,” she said.

Because women with preeclampsia have a twofold increased risk for stroke and a fourfold risk for high BP later in life, the guideline recommends that pregnant women with chronic primary or secondary hypertension or previous pregnancy-related hypertension take low-dose aspirin from the 12th week of gestation until delivery. The guideline also recommends that severe hypertension in pregnancy (systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) be treated with antihypertensive medications known to be safe and effective in pregnant women.

BP measurement before prescribing oral contraceptives is recommended because of the elevated risk for stroke in women with high BP who take oral contraceptives, especially if they have other risk factors for stroke. The guideline also states that hormone therapies are not effective for stroke prevention.

According to the guideline, there is an elevated risk for stroke in women who smoke and have migraines with aura, so those women should be counseled to stop smoking. Further, there is evidence that treatments to reduce the frequency of migraines may reduce the risk for stroke.

Active screening for AF should be conducted in women aged 75 years and older because older women with AF have a high risk for stroke, and women with paroxysmal or permanent AF and other risk factors should be prescribed a novel oral anticoagulant, according to the guideline.

Other topics covered by the guideline include diet, physical activity and carotid endarterectomy.

Goal to raise awareness

One challenge is ensuring that the guidelines are known to all specialties, experts Cardiology Today interviewed said.

“This is an area that falls into a gap where no group of physicians is taking the primary responsibility for reducing strokes before they happen or reducing the chance of a second event,” Gina Lundberg, MD, FACC, assistant professor of medicine at Emory School of Medicine, director of the Emory Women’s Heart Center at Emory University and AHA spokeswoman, said in an interview.

“My opinion is that cardiologists … don’t really see this as our area. [We] put that off to the neurologists. And the neurologists really aren’t involved in risk reduction through cholesterol, BP, blood-clotting factors and inflammatory biomarkers,” she said.

Calling attention to the stroke risks of women who had pregnancies associated with high BP or preeclampsia may be the greatest accomplishment of the guidelines because it addresses an unmet need, Lundberg said. “This is a gap in medical care, that these women aren’t being told that they need to be followed long term because they are at risk for stroke and MI and might want to start seeing a preventive cardiologist by age 40 or 45.”

Brian Silver, MD, FAHA, director of the stroke center at Rhode Island Hospital and associate professor of neurology at Brown University, agreed, noting that the recommendations also need to be heeded by clinicians who are not stroke specialists.

“The question is how well is this going to get disseminated out into primary care physicians’ offices,” he told Cardiology Today. “Often, it takes some time for a specialty specific guideline to make it into the general universe. Here in the stroke world, we are very well-versed with these kinds of issues, so a lot of the recommendations in the guidelines might be obvious to us, but these are not necessarily messages that have made their way out to others.”

Overall, the new guideline is important — and long overdue, Lundberg said. “The first guidelines for the prevention of heart disease in women came out in 2004, with updates in 2007 and again in 2011. Here we are, in 2014, and we finally have a stroke-prevention guideline in women. We were lagging 10 years behind on this one.”

The important role of BP

BP control is the most important way to lower risk for stroke, experts told Cardiology Today.

“BP is the single most important modifiable risk factor for stroke in men and in women,” said Stanley Tuhrim, MD, professor of neurology, geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai and director of the Mount Sinai Stroke Center. “And, women are less likely to have their BP well-controlled than are men with high BP.”

Marian Limacher, MD, FACC, FAHA, senior associate dean for faculty affairs and professional development and AHA endowed professor of cardiovascular research at University of Florida College of Medicine in Gainesville, said BP control is particularly important for prevention of stroke in women who have gone through menopause.

“BP tends to rise with age, particularly after menopause for women, so getting BP measured, starting proper treatment and then regular follow-up is important for getting BP in an acceptable range,” she said. “It may take more than one medication. It may take switching medications, but it needs to be monitored and managed. That’s something we need to continue to emphasize … particularly for women as they get over the age of 65 and to the highest risk for stroke.”

Bushnell noted, however, that “more research is needed to determine whether women have varying responses to BP medication with men in regards to stroke prevention. In addition, dosing may be different in men vs. women.”

For healthy women aged 65 years or older, aspirin has been shown to reduce stroke risk, and more women of that age have been advised to start an aspirin regimen in recent years, said Suzanne Steinbaum, DO, FACC, director of women’s heart health at Lenox Hill Hospital, New York City, and spokeswoman for the AHA’s Go Red for Women campaign.

“More patients are getting preventive treatments and more women are being screened,” she said. “There was a very long time where women were not being treated, diagnosed or even acknowledged as having cardiovascular disease. Now, women are getting tested more than they were and being put on preventive measures, like statins and aspirin and, when necessary, beta-blockers and [warfarin], that prevent stroke mortality.”

Aggressive treatment of risk factors

Treatment of women with AF will go a long way toward reducing stroke risk, Limacher said.

“For women who meet the recommended guidelines for beginning anticoagulation therapy with AF, achieving and maintaining adequate anticoagulation status is very important,” she said. “Women are slightly less likely to be started on anticoagulation for AF [than men], and that is a mistake unless there are overwhelming risks that would prevent the use of an anticoagulant.”

Lundberg said outdated perceptions of risks for women may play a role in the underprescription of anticoagulation therapy.

“We have to make an effort to get the word out to primary care doctors that we have to be aggressive in treating women with AF with an anticoagulant,” she said. “One thing that came out when the 2011 update to the guidelines on the prevention of heart disease in women came out was that women with AF were not being put on [anticoagulation] at the rate they should. In the CHA2DS2-VASC score for people with AF, if you’re a woman and you’re 65, that’s 2 points, and you’re supposed to be on anticoagulants. Women are at higher risk, in general, and need to start younger on the anticoagulants. Sometimes, [doctors] look at frail older women and say, ‘The risk is too high, you’ll bleed, you’ll fall.’ But the truth is, the risk for stroke is higher.”

Instead, she said, a woman’s CHA2DS2-VASC and HAS-BLED scores should be calculated, and those scores should provide insight into whether a patient’s stroke risk or bleeding risk is higher.

The new guideline might also prompt more comprehensive treatment of women who have migraine with aura, said Erica Camargo Faye, MD, PhD, MMSc, assistant in neurology at Massachusetts General Hospital, the Massachusetts General Hospital Institute for Heart, Vascular and Stroke Care, and instructor in neurology at Harvard Medical School.

“Neurologists see many patients with migraine with aura, and usually do not address vascular risk factors in these patients,” she said. “Bringing that about might … make clinicians much more aware of the importance of migraine with aura and that patients do need to have vascular risk factors addressed as well, especially smoking and oral contraceptive use.”

Controlling the frequency of migraines with aura is important, Bushnell said, “although the precise strategy for doing so is not yet established.”

If surgical therapy is to be considered, carotid endarterectomy may be the most appropriate choice for many women, experts said.

The guideline recommends that women undergoing carotid endarterectomy, even those with diabetes, should take aspirin, or clopidogrel if they cannot tolerate aspirin. It also notes that although the CREST trial showed that women who underwent carotid artery stenting may have higher risk for the composite outcome of stroke, MI or death compared with those who underwent carotid endarterectomy, “this finding should be interpreted with caution pending confirmation from other trials.”

“The studies are not as large or as inclusive of women as they could be, but it appears that carotid artery endarterectomy is better in women than stenting, at least in older women,” Limacher said. “It may be that use of carotid endarterectomy should be considered in appropriate women candidates rather than jumping to stenting or medication in the guideline-indicated situation.”

Lifestyle factors

The guideline’s lifestyle recommendations include regular physical activity, smoking cessation, limited alcohol consumption and a diet rich in fruits, vegetables, grains, nuts and olive oil, and low in saturated fat.

Beyond that, a good strategy for reducing stroke risk is to reduce stress and control depression as much as possible, said Steinbaum, author of Dr. Suzanne Steinbaum’s Heart Book: Every Woman’s Guide to a Heart-Healthy Life. “We don’t know if antidepressants are helpful; the data haven’t shown that,” she said. “One hypertension guideline looked at transcendental meditation, and it was one of the most effective ways to lower BP. I would love to say that a pill could treat stress and depression, but I cannot. [A patient] has to be willing to adopt lifestyle measures to deal with these issues.”

Camargo Faye agreed. “Some data suggest that meditation may help control BP, and subsequently that may reduce your risk for stroke and CVD,” she said. “I emphasize to patients that they should try to lead a happy life; if possible, to be very active in their community, interact with their families and friends … and really keep their brain active. Those make a huge difference in terms of stroke recovery and also in decreasing the risk for stroke as well.”

In addition, Tuhrim said, “Obesity and other factors involved with metabolic syndrome, including hyperlipidemia and diabetes, are somewhat more prevalent in women and should not be ignored.”

Female-specific risk score

The guideline also calls for development of a female-specific stroke risk score. Bushnell told Cardiology Today that the risk score should include “pregnancy complications [such as] preeclampsia and gestational diabetes, hormonal contraception and hormone therapy for women well past menopause. A thorough evaluation for occult AF would likely benefit older women. It would be interesting to test the new AHA/American College of Cardiology CV risk calculator with these additional woman-specific factors to see if they are still associated with stroke after accounting for cholesterol and BP.”

Steinbaum said it also might make sense to include psychosocial and depression factors, but noted that hormonal issues are likely to be the key to developing an accurate score. “When did you start menses? When did you go into menopause? What about women who had surgical oophorectomies and had immediate-onset menopause?” she said. “These hormonal fluctuations matter so much in the risk for CVD and stroke, and they need to go into the risk analysis.”

Camargo Faye questioned whether there are enough data to include hormone therapy into a risk score, but said there are for preeclampsia, oral contraceptive use and migraine with aura.

“I would also highlight frailty and depression,” she said. “Many geriatric studies have looked at a frailty risk score as a predictor of stroke, cardiovascular outcomes and mortality, so I do think that would be a useful measure to test in a female-specific stroke score. One could use hand-grip strength or walking speed as surrogate frailty measures. Particularly for women, depression is so important and does seem to play a significant role in the appearance of stroke and also in stroke recovery.”

More research needed

Some approaches to stroke prevention work equally well for men and women, but the effects of others differ by sex, and more research is needed to better understand why.

“Women and men differ, from the most basic level (our chromosomes are different), gonadal hormone exposure and societal factors,” Bushnell said. “This likely influences the incidence of stroke and the response to therapies. We must explore and understand these differences if we are to provide the best prevention and treatment options for both men and women.”

Fulfilling that task should be a high priority because the consequences of failing could be significant, Steinbaum said.

“Women’s symptoms have been more dismissed, and women have notoriously been less treated,” she said. “Patients need to be their own advocates, and doctors need to be more sensitive to the fact that all these risk factors that they never thought about in men, they now need to think about. Unless we change our practice with the times and the research, we are going to miss preventing stroke in many women.” – by Erik Swain

Disclosure: Limacher was an invited reviewer of the guideline on prevention of stroke in women. Bushnell, Camargo Faye, Lundberg, Silver, Steinbaum and Tuhrim report no relevant financial disclosures.