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Stroke prevention in women: risk factors


In February 2014, the American Heart Association [ AHA ] /American Stroke Association [ ASA ] released their first guideline focused on stroke prevention in women.
This new guideline highlights unique risk factors for stroke in women, including oral contraception and hormone therapy, and pregnancy-associated disorders, such as preeclampsia, that may have long-lasting consequences on a woman's health.
It also addresses hypertension; atrial fibrillation; migraine headache with aura; and the epidemiology of types of stroke, such as aneurysmal subarachnoid hemorrhage and cerebral vein thrombosis, that are predominant in women.

Cheryl Bushnell ( Wake Forest Baptist Medical Center, Winston-Salem, NC; USA ) and Louise McCullough ( University of Connecticut Health Center, Farmington, CT; USA ) did a synopsis of the guideline summarizes the evidence about risk factors for stroke in women and suggests prevention strategies.

Risk factors for stroke

A) Hypertension in nonpregnant women - Hypertension, the most modifiable risk factor for stroke, is more prevalent in women than men. Hypertension is more often poorly controlled in older women; only 23% of women versus 38% of men older than 80 years have a blood pressure less than 140/90 mm Hg. There is currently no evidence that antihypertensive treatments differentially affect blood pressure response or stroke prevention by sex, but many trials of antihypertensive agents do not report sex-specific analysis for efficacy or adverse effect profiles. Moreover, there are major evidence gaps about appropriate drug choices, treatment resistance, adherence, and hormone-dependent and -independent approaches to blood pressure treatment by sex.

B) Atrial fibrillation - Sex differences in atrial fibrillation include a higher prevalence and a higher associated risk for thromboembolic events in women. The effect of this epidemiology has translated into the development of risk scores for patients with atrial fibrillation, with an additional point given for female sex in the CHA2DS2-VASc ( congestive heart failure / left ventricular dysfunction, hypertension, age 75 years or more, diabetes mellitus, stroke / transient ischemic attack [ TIA ]/ thromboembolism, vascular disease, age 65 to 74 years, sex category ) score. Therefore, use of risk stratification tools that account for age- and sex-specific differences in the incidence of stroke is recommended. Women, particularly those older than 75 years, should be actively screened for atrial fibrillation with pulse rate measurement and electrocardiography as appropriate ( class I; level of evidence B ). Antiplatelet therapy for women with lone atrial fibrillation who are aged 65 years or younger is also suggested.

C) Migraine headache with aura - Women are 4 times more likely than men to have migraine headache. Although the absolute risk for stroke associated with migraine headache is low, the association between migraine headache with aura and stroke seems strongest in women younger than 55 years. The frequency of migraine headache may also be associated with stroke.
A decrease of frequency of migraine headache as a possible strategy to reduce the risk for stroke suggest reducing, although there is no evidence that specific treatment strategies ( for example, calcium-channel blockers, beta-blockers, and antiepileptic drugs ) reduce the risk for stroke. Given a synergistic relationship between smoking and migraine headache with aura, smoking cessation treatments and counseling for persons who smoke and have migraine headache are recommend. Finally, clinicians should use caution women with migraine headache about the use of oral contraceptives.

D) Hormonal contraception - The use of oral contraceptives is a risk factor for stroke in young women, increasing the risk from 1.4- to 2.0-fold compared with that of women who do not use these agents. The absolute risk is low, approximately 2 events per 10000 women per year with the use of the lowest-dose formulation, according to a recent study from Denmark. The risk for stroke among women using oral contraceptives increases exponentially from 3.4 per 100 000 women aged 15 to 19 years to 64.4 per 100000 women aged 45 to 49 years. Factors that could further increase risk for stroke include prior thromboembolic events, hypertension, cigarette smoking, hyperlipidemia, diabetes, and obesity. Accordingly, it is recommended to identify women with such risk factors and to increase efforts to manage modifiable risk factors in women who use oral contraceptives.
The guideline also addresses prothrombotic mutations and biomarkers that increase the risk for stroke in a synergistic manner. Studies have shown that markers of endothelial dysfunction, such as von Willebrand factor and ADAMTS13 ( a disintegrin and metalloproteinase with the thrombospondin type 1 repeat 13 ), increase the risk for stroke more than 10-fold in women who use oral contraceptives compared with those who do not.
Although many prothrombotic mutations increase the risk for stroke in women using oral contraceptives, it is not recommended screening for these mutations before starting oral contraceptive therapy because of their low prevalence in otherwise healthy women, especially in the absence of a positive family history.
Additional research is needed to better characterize the risk for hemorrhagic stroke with oral contraceptive use, focusing on older women who may use these agents until menopause, members of underrepresented minority groups, genetic makeup, and parity. The study of clinically available biomarkers, such as von Willebrand factor, is warranted in broader populations of women.

E) Menopause and hormone replacement - Menopause, particularly younger age at menopause, and risk for stroke may be related, but evidence defining such a relationship is inconsistent. Whether natural versus surgical menopause is associated with risk for stroke is also unclear. However, the use of hormone therapy in postmenopausal women is a unique risk factor for stroke in women.
In general, hormone therapy is associated with an increased risk for stroke and is not recommended for primary or secondary prevention of this condition. Many gaps remain in research about the magnitude of harms and tradeoffs between benefits and risks of hormone therapy. These gaps concern treatment of subgroups of women who are at high risk for stroke after menopause; treatment of women who are early in the peri- or postmenopause period; and the optimum timing, dosage, type, and route of administration that could enhance vascular health.

F) Depression and psychosocial stress - Several cohort studies and a meta-analysis have identified depression and psychosocial stress as factors that increase the risk for incident stroke by 25% to 45% in women. The odds ratios across studies that included both men and women are similar to those of studies that included only men or only women, making it difficult to state conclusively that women with these conditions have a higher risk for stroke than men.
More research is needed to understand the subgroups of women at risk, such as those who are treated versus not, and the method of determining depression and psychosocial stress. ( Xagena )

Bushnell C, McCullough L, Ann Intern Med 2014;160:853-857

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