- In the United States, more than half (53.5%) of the estimated 795,000 new or recurrent strokes occur among women annually, resulting in ≈55,000 more stroke events in women than men.
- Most (87%) strokes are ischemic (IS), with the remainder hemorrhagic (10% intracerebral [ICH] and 3% subarachnoid [SAH]).
Table 1. Stroke Risk Factors, Categorized by Those That Are Sex-Specific, Stronger or More Prevalent in Women, or Similar Between Women and Men
|Risk Factor||Sex-Specific||Stronger or More Prevalent in Women||Similar Prevalence in Men and Women but Unknown Difference in Impact|
|Oral contraceptive use||X|
|Postmenopausal hormone use||X|
|Changes in hormonal status||X|
|Migraine with aura||X|
|Prior cardiovascular disease||X|
Prevention of Preeclampsia
- Women with chronic primary or secondary hypertension or previous pregnancy-related hypertension should take low-dose aspirin from the
12th week of gestation until delivery (I-A).
- Calcium supplementation (of ≥1 g/d, orally) should be considered for women with low dietary intake of calcium (<600 mg/d) to prevent preeclampsia (I-A).
Treatment of Hypertension in Pregnancy and Postpartum
- Severe hypertension in pregnancy should be treated with safe and effective antihypertensive medications, such as methyldopa, labetalol, and nifedipine, with consideration of maternal and fetal side effects (I-A).
- Consideration may be given to treatment of moderate hypertension in pregnancy with safe and effective antihypertensive medications, given the evidence for possibly increased stroke risk at currently defined systolic and diastolic BP cutoffs, as well as evidence for decreased risk for the development of severe hypertension with treatment (although maternal-fetal risk-benefit ratios have not been established) (IIa-B).
- Atenolol, angiotensin receptor blockers, and direct renin inhibitors are contraindicated in pregnancy and should not be used (III-C).
- After giving birth, women with chronic hypertension should be continued on their antihypertensive regimen, with dosage adjustments to reflect the decrease in volume of distribution and glomerular filtration rate that occurs after delivery. They should also be monitored carefully for the development of postpartum preeclampsia (IIa-C).
Prevention of Stroke in Women With a History of Preeclampsia
- Because of the increased risk of future hypertension and stroke 1-30years after delivery in women with a history of preeclampsia (B), it is reasonable to (1) consider evaluating all women starting 6 months to 1 year postpartum, as well as those who are past childbearing age, for a history of preeclampsia/eclampsia and document their history of preeclampsia/eclampsia as a risk factor, and (2) evaluate and treat for cardiovascular risk factors including hypertension, obesity, smoking, and dyslipidemia (IIa-C).
Cerebral Venous Thrombosis (CVT)
- In patients with suspected CVT, routine blood studies consisting of a complete blood count, chemistry panel, prothrombin time, and activated partial thromboplastin time should be performed (I-C).
- Screening for potential prothrombotic conditions that may predispose a person to CVT (eg, use of contraceptives, underlying inflammatory disease, infectious process) is recommended in the initial clinical assessment (I-C).
- Testing for prothrombotic conditions, including protein C, protein S, or antithrombin deficiency; antiphospholipid syndrome; prothrombin G20210A mutation; and factor V Leiden can be beneficial for the management of patients with CVT. Testing for protein C, protein S, and antithrombin deficiency is generally indicated 2-4 weeks after completion of anticoagulation. There is a very limited value of testing in the acute setting or in patients taking warfarin (IIa-B).
- In patients with provoked CVT (associated with a transient risk factor), vitamin K antagonists with a target INR of 2.0-3.0 may be continued for 3-6 months (IIb-C).
- In patients with unprovoked CVT, vitamin K antagonists may be continued for 6-12 months, with a target INR of 2.0-3.0 (IIb-C).
- For patients with recurrent CVT, VTE after CVT, or first CVT with severe thrombophilia (ie, homozygous prothrombin G20210A; homozygous factor V Leiden; deficiencies of protein C, protein S, or antithrombin; combined thrombophilia defects; or antiphospholipid syndrome), indefinite anticoagulation with a target INR of 2.0-3.0 may be considered (IIb-C).
- For women with CVT during pregnancy, LMWH in full anticoagulant doses should be continued throughout pregnancy, and LMWH or vitamin K antagonist with a target INR of 2.0-3.0 should be continued for ≥6 weeks postpartum (for a total minimum duration of therapy of 6 months) (I-C).
- It is reasonable to advise women with a history of CVT that future pregnancy is not contraindicated. Further investigations regarding the underlying cause and a formal consultation with a hematologist or maternal-fetal medicine specialist are reasonable (IIa-B).
- It is reasonable to treat acute CVT during pregnancy with full-dose LMWH rather than unfractionated heparin (IIa-C).
- For women with a history of CVT, prophylaxis with LMWH during future pregnancies and the postpartum period is reasonable (IIa-C).
Oral Contraceptives (OCs)
- OCs may be harmful in women with additional risk factors (eg, cigarette smoking, prior thromboembolic events) (III-B).
- Among OC users, aggressive therapy for stroke risk factors may be reasonable (IIb-C).
- Routine screening for prothrombotic mutations before initiation of hormonal contraception is not useful (III-A).
- Measurement of BP before initiation of hormonal contraception is recommended (I-B).
- HT (CEE with or without medroxyprogesterone) should NOT be used for primary or secondary prevention of stroke in postmenopausal women (III-A).
- Selective estrogen receptor modulators, such as raloxifene, tamoxifen, or tibolone, should NOT be used for primary prevention of stroke (III-A).
Migraine With Aura
- Because there is an association between higher migraine frequency and stroke risk, treatments to reduce migraine frequency might be reasonable, although evidence is lacking that this treatment reduces the risk of first stroke (IIb-C).
- Because of the increased stroke risk seen in women with migraine headaches with aura and smoking, it is reasonable to strongly recommend smoking cessation in women with migraine headaches with aura (IIa-B).
Obesity, Metabolic Syndrome, and Lifestyle Factors
- A healthy lifestyle consisting of regular physical activity, moderate alcohol consumption (<1 drink/d for nonpregnant women), abstention from cigarette smoking, and a diet rich in fruits, vegetables, grains, nuts, olive oil, and low in saturated fat (such as the DASH [Dietary Approaches to Stop Hypertension] diet) is recommended for primary stroke prevention in women with cardiovascular risk factors (I-B).
- Lifestyle interventions focusing on diet and exercise are recommended for primary stroke prevention among individuals at high risk for stroke (I-B).
Atrial Fibrillation (AF)
- Risk stratification tools in AF that account for age- and sex-specific differences in the incidence of stroke are recommended (I-A).
- Considering the increased prevalence of AF with age and the higher risk of stroke in elderly women with AF, active screening (in particular of women >75 years of age) in primary care settings using pulse taking followed by an ECG as appropriate is recommended (I-B).
- Oral anticoagulation in women aged ≤65 years with AF alone (no other risk factors, women with CHADS2=0 or CHA2DS2-VASc=1) is NOT recommended (III-B). Antiplatelet therapy is a reasonable therapeutic option for selected low-risk women (IIa-B).
- New oral anticoagulants are a useful alternative to warfarin for the prevention of stroke and systemic thromboembolism in women with paroxysmal or permanent AF and prespecified risk factors (according to CHA2DS2-VASc) who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance ≤15 mL/min), lower weight (<50 kg), or advanced liver disease (impaired baseline clotting function) (I-A).
Strategies for Prevention of Stroke in Women
- Women with asymptomatic carotid stenosis should be screened for other treatable risk factors for stroke, and appropriate lifestyle changes and medical therapies should be instituted (I-C).
- In women who are to undergo CEA, aspirin is recommended unless contraindicated, because aspirin was used in every major trial that demonstrated efficacy of CEA (I-C).
- Prophylactic CEA performed with <3% morbidity/mortality can be useful in highly selected patients with an asymptomatic carotid stenosis (minimum 60% by angiography, 70% by validated Doppler ultrasound) (IIa-A).
- For women with recent TIA or IS within the past 6 months and ipsilateral severe (70%-99%) carotid artery stenosis, CEA is recommended if the perioperative morbidity and mortality risk is estimated to be <6% (I-A).
- For women with recent transient ischemic attack (TIA) or ischemic stroke (IS) and ipsilateral moderate (50%-69%) carotid stenosis, carotid endarterectomy (CEA) is recommended depending on patient-specific factors, such as age and comorbidities, if the perioperative morbidity and mortality risk is estimated to be <6% (I-B).
- When CEA is indicated for women with TIA or stroke, surgery within 2 weeks is reasonable rather than delaying surgery, if there are no contraindications to early revascularization (IIa-B).
- Aspirin therapy (75-325 mg/d) is reasonable in women with diabetes mellitus unless contraindicated (IIa-B).
- If a high-risk (ie, 10-year predicted CVD risk ≥10%) woman has an indication for aspirin but is intolerant of aspirin therapy, clopidogrel should be substituted (I-B).
- Aspirin therapy can be useful in women ≥65 years of age (81 mg/d or 100 mg every other day) if BP is controlled and the benefit for IS and MI prevention is likely to outweigh the risk of gastrointestinal bleeding and hemorrhagic stroke (IIa-B) and may be reasonable for women <65 years of age for IS prevention (IIb-B).
Table 2. Summary of Antihypertensive Drugs Used During Pregnancy
|Category||Maternal Side Effects||Teratogenicity or Fetal-Neonatal Adverse Effects||Class/Level of Evidence|
|Centrally acting α2-adrenergic agonist (eg, methyldopa)||Sedation, elevated LFTs, depression||No||IIa-C|
|β-Blockers (atenolol)||Headache||Associated with fetal growth restriction||III-B|
|β-Blockers (pindolol, metoprolol)||Headache||Possible fetal growth restriction, neonatal bradycardia||IIa-B|
|Calcium channel blockers (eg, nifedipine)||Headache; possible interaction with magnesium sulfate; may interfere with labor||No||I-A|
|Combined α-β blockers (labetalol)||May provoke asthma exacerbation||Possible neonatal bradycardia||IIa-B|
|Hydralazine||Reflex tachycardia, delayed hypotension||Neonatal thrombocytopenia, fetal bradycardia||III-B|
|ACE inhibitors, angiotensin receptor blockers, renin inhibitors||Skeletal and cardiovascular abnormalities, renal dysgenesis, pulmonary hypoplasia||III-C|
|Modified from Umans JG, Abalos EJ, Lindheimer MD. Antihypertensive treatment.|
In: Lindheimer MD, Roberts JM, Cunningham FG, eds. Chesly’s
Hypertensive Disorders in Pregnancy. Amsterdam: Academic Press,
Elsevier; 2009:369–338. With permission from Elsevier, Copyright © 2009.