Stroke in Women: Risk, Prevention, and Treatment

Each year in the United States, stroke affects more than 795,000 people and results in approximately 140,000 deaths.¹ Although stroke is the fifth leading cause of death among Americans overall, it is the third leading cause of death among women, partially because of the longer life expectancy of women compared with men.² In addition, the risk for stroke is especially elevated among black and Hispanic women.³

Various life stages and other factors specific to women, such as menarche and menopause, have been linked to their increased stroke risk. For example, women with an age at menarche of ≤10 years were found to have a higher stroke risk later in life vs those who experienced menarche at 13 years (risk ratio, 1.16; 95% CI, 1.09-1.24).⁴ An elevated stroke risk was also observed among women whose age of menarche was ≥17 years vs 13 years (risk ratio, 1.13; 95% CI, 1.03-1.24).

A shorter reproductive period has been linked to an increased risk for stroke, likely as a result of earlier menopause, and numerous findings have demonstrated a connection between combination oral contraceptives (OCPs) and elevated stroke risk.^5,6

For more details about differences in stroke risk, prevention, and treatment in women, Neurology Advisor checked in with Elisabeth B. Marsh, MD, an associate professor of neurology at the Johns Hopkins School of Medicine, and medical director of the Johns Hopkins Bayview Medical Center Comprehensive Stroke Program, Baltimore, Maryland; and Kristy Yuan, MD, an assistant professor of clinical neurology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

Neurology Advisor: What are some key differences pertaining to stroke in women vs men, in terms of risk, prognosis, or otherwise?

Dr Marsh: More than 50% of strokes occur in women. Women share many of the same stroke risk factors as men — high blood pressure, diabetes, cholesterol, obesity, and smoking — particularly after menopause. They also tend to be older at the time of their stroke, which means they are more likely to be widowed or living alone. This can result in poorer functional outcomes. Studies show that women are less likely to achieve independence after a stroke, and more likely to die as a result.⁷

Along with typical stroke risk factors, there are factors that are more specific to women. Pregnancy is actually a relative hypercoagulable state in which the blood is more prone to clot. Autoimmune diseases such as lupus can increase risk for stroke, along with migraine and OCP use. That is not to say that every woman with lupus or migraine or taking OCPs will have a stroke, only that her physician should consider these issues and how they relate to her overall vascular risk.

Finally, similar to heart attacks, women having a stroke can present with different symptoms than their male counterparts. The acute onset of hiccups or dizziness, complaints that are often overlooked, can be the initial presentation. In part because of these atypical symptoms, women are less likely to seek treatment for these symptoms in a window for potential treatment (within 4.5 hours from symptom onset).

Neurology Advisor: How are these addressed in practice, including prevention and treatment measures?

Dr Marsh: Because of these differences, primary stroke prevention in a woman of child-bearing age extending through her postmenopausal years is crucial, along with education on potential stroke signs and symptoms and the importance of rapid detection and treatment to improve outcomes.

Dr Yuan: Some major recommendations in stroke prevention in women include the following, based on the 2014 American Heart Association guidelines on stroke prevention in women:⁸

• Pregnancy and hypertension (HTN)

o    Women with chronic HTN or previous pregnancy-related HTN should take low-dose aspirin from the 12th week of gestation to delivery. Women who developed preeclampsia during pregnancy should be closely followed for future development of chronic HTN after pregnancy.

o    Treatment of HTN during and after pregnancy should involve agents that are safe for maternal and fetal adverse effects, such as methyldopa, labetalol, and nifedipine. Atenolol, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers are contraindicated in pregnancy.

• Cerebral venous thrombosis during pregnancy

o    It is reasonable to treat with low-molecular-weight heparin (eg, Lovenox) and continue for ≥6 weeks postpartum for a minimum total duration of 6 months.

o    Test for underlying conditions of hypercoagulability.

o    For women with a history of cerebral venous thrombosis, prophylaxis with Lovenox during future pregnancies and the postpartum period is reasonable.

o    Future pregnancy is not contraindicated for women with a history of cerebral venous thrombosis, but close follow-up in a high-risk obstetric clinic is recommended.

• OCPs

o    OCPs are not recommended in women with other vascular risk factors, especially HTN and smoking, and prior venous thromboembolism.

o    Progestin-only formulations are not generally associated with ischemic stroke.

• Hormone replacement therapy for menopause

o    Conjugated equine estrogen with or without medroxyprogesterone should not be used in primary or secondary prevention of stroke in postmenopausal women.

• Migraine with aura

o    There is increased risk for stroke in women who smoke and have migraines with aura, so encourage smoking cessation in those patients.

• Alcohol consumption and cardiovascular health

o    The recommended limits are less than 1 drink per day for nonpregnant women and less than 2 drinks per day for men.

• Atrial fibrillation

o    Active screening for atrial fibrillation is recommended in women ˃75 years with the clinical exam and an electrocardiogram in the office.

o    Low-dose aspirin is recommended over anticoagulant therapy (such as warfarin) in women with low cardiovascular risk.

Neurology Advisor: What should be the focus of future research in this area?

Dr Marsh: Along with ways to clinically improve functional outcomes and quality of life for women after stroke, an important area of research is the effects of hormonal differences, both on the underlying pathophysiology or cause of the stroke and on the way the brain recovers after damage.

Dr Yuan: [Studies should investigate] stroke prevention and education regarding stroke risk in the postpartum period. Acute stroke therapies and safety in pregnant women should also be examined. The clinical trials on tissue plasminogen activators and thrombectomy for acute stroke excluded women, and although the effectiveness is presumed good for women, the safety of mother and fetus need to be better documented through registries and prospective data. Another important topic for inquiry is the compounded stroke risk with OCPs, HTN, and smoking in young women.

References

1. Centers for Disease Control and Prevention. Stroke facts. https://www.cdc.gov/stroke/facts.htm. Accessed on March 1, 2018.
2. Demel SL, Kittner S, Ley SH, McDermott M, Rexrode KM. Stroke risk factors unique to women. Stroke. 2018;49(3):518-523.
3. Kaplovitch E, Anand SS. Stroke in women: recognizing opportunities for prevention and treatment. Stroke. 2018;49(3):515-517.
4. Canoy D, Beral V, Balkwill A, et al; Million Women Study Collaborators. Age at menarche and risks of coronary heart and other vascular diseases in a large UK cohort. Circulation. 2015;131(3):237-244.
5. Ley SH, Li Y, Tobias DK, et al. Duration of reproductive life span, age at menarche, and age at menopause are associated with risk of cardiovascular disease in women. J Am Heart Assoc. 2017;6(11):e006713.
6. Roach RE, Helmerhorst FM, Lijfering WM, Stijnen T, Algra A, Dekkers OM. Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev. 2015;(8):CD011054.
7. Gall S, Phan H, Madsen TE, et al. Focused update of sex differences in patient reported outcome measures after stroke. Stroke. 2018;49(3):531-535.
8. Bushnell C, McCullough LD, Awad IA, et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Epidemiology and Prevention; 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;45(5):1545-1588.