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 (Class IIa; Level of Evidence B) and may be reasonable for women <65 years of age for IS prevention (Class IIb; Level of Evidence B).21 Data Shaping Development and Validation of Risk Scores Use of Sex-Specific Stroke Risk Prediction Scores Risk scores have been advocated to clinically classify indi- viduals according to their overall risk to guide prevention and treatment recommendations. The goal of such scores is to accurately classify individuals as high or low risk so that high-risk individuals receive appropriate interventions to reduce risk. Although there are several general cardiovascular risk there are fewer stroke-specific scores. Risk prediction models that are specific to women have not been developed. Furthermore, whether risk factors differ by age and racial/ethnic group has not been established. The Framingham stroke risk calculator does take sex into The number of points assigned to particular con- ditions differs by sex, with diabetes mellitus, systolic BP, and AF garnering a higher number of points in women than men, whereas women with existing CVD receive fewer points than do men (Table 16). Moreover, the 10-year probability of stroke from the Framingham Stroke Risk Score (FSRS) is lower for women than for men with the same score (Table 17); however, few other widely validated stroke prediction scores for the general population are available. Data in minorities and women are limited. The FSRS was derived in a predominantly white, middle- to older-aged population in a single community. The FSRS was applied to the Cardiovascular Health Study (CHS) population of men and women >65 years of age, and it was found that the FSRS model predicted stroke less effectively in elderly women than men. A CHS stroke risk model and applet were created that improved discrimination in women (area under the receiver operating characteristic curve of 0.73 for FSRS in women compared with 0.77 for the CHS model in women; Additional variables included in the CHS score included time to walk 15 feet (functional status) and creati- nine. When the FSRS was used to evaluate risk in a group of elderly French men and women (aged 65 84 years at base- line), it overestimated the risk substantially (by a factor of 4.4 in women and 3.7 in men), which led to a recalibrated stroke score for that population.442 Therefore, comparative data are needed on how well risk scores perform in women versus men and in different racial and ethnic populations. Several stroke risk scores were developed exclusively for use in men,443,444 but woman-specific models are needed to more accurately reflect risk across the lifespan. Specific risk factors are unique to or more common in women that have not been included in traditional risk assessment (Table 3). Prospective research is needed for these woman-specific risk factors, including pregnancy-related risk factors and hormonal exposure (OCs and postmenopausal HT), as well as changes in hormone status across the lifespan (menarche, menopause, and oophorectomy). For example, preeclampsia clearly increases risk of stroke in the peripartum period and has been listed as a risk factor for CVD in women in the 2011 AHA Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women 21 ; however, relatively lim- ited data on long-term risk of stroke among women with a history of preeclampsia are available.180 In addition, several less traditional risk factors, including psychosocial stress and depression, were important in the INTERSTROKE study92 and other observational studies398,399 but are not included in tradi- tional risk scores.440,445 Women have higher rates of depression, and thus, these factors may be of greater impact for women.446 Additionally, there are potential differences in the risk of stroke among older individuals with AF, with higher rates in women despite warfarin therapy, as discussed above.372 Whether bio- markers, in addition to lipid measures, additionally contribute to risk stratification in women is unclear. C-reactive protein, an inflammatory marker that is also included in the Reynolds Cardiovascular Risk Score,439,447 was found to improve predic- tion of risk of IS, particularly cardioembolic stroke, in older women in the WHI.448 Lipoprotein-associated phospholipase was associated with improvement in the prediction of large- Additional evaluation of other biomarkers for risk prediction will be of continued interest. Woman-Specific Risk Score: Summary and Gaps Consideration of the risk factors that are unique to women and are more prevalent or differentially increase risk, compared with men, may improve the accuracy of stroke risk assessment compared with current risk scores. This is especially true for younger women of reproductive age. Prospective data on the long-term stroke risk of women with a history of preeclampsia Table 16. Risk Factors and Points Included in the Framingham Stroke Risk Score for 10-Year Stroke Risk Prediction in Women* Diabetes mellitus No Yes Cigarette smoking No Yes Prior CVD No Yes AF No Yes LVH on ECG No Yes Yes AF indicates atrial fibrillation; CVD, cardiovascular disease; ECG, electrocardiogram; LVH, left ventricular hypertrophy; and SBP, systolic blood pressure. *Available at http://www.framinghamheartstudy.org/risk-functions/stroke/stroke.php. CVD is defined as any of the following: history of myocardial infarction, angina pectoris, coronary insufficiency, intermittent claudication, or congestive heart failure. Table 17. Ten-Year Stroke Probability in Women According to Framingham Stroke Risk Score Points Probability, % Points Probability, % Points Probability, % Bushnell et al Guidelines for Prevention of Stroke in Women 1575 and other pregnancy-related complications are also needed.449 Further development of stroke risk prediction models in women could be achieved by use of data from large, diverse longitudinal studies including the WHI, WHS, Nurses Health Study, ARIC study, Multi-Ethnic Study of Atherosclerosis (MESA), and Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Sex-specific and race- and eth- nic-specific analyses need to be conducted explicitly to deter- mine whether current and future risk scores perform equally well in white, black, and Latina women. Conclusions and Summary In this guideline, we have summarized the current evidence and provided summaries and gaps for prevention focused on the risk factors that are either unique to or more common in women than men. Some of the recommendations in this guideline were formerly associated with other prevention guidelines but have been assimilated because of the focus on women. In addition, we have summarized the data that sup- port the development of woman-specific stroke risk profiles, which might more accurately reflect a woman s future risk of stroke than some of the currently available stroke risk profiles. Prevention efforts for women would be enhanced if future epidemiological studies provided more detail on stroke sub- type, especially hemorrhagic stroke, in addition to accounting for age and sex. Similarly, it is important to improve stroke awareness and provide more rigorous education to women at younger ages, including childbearing ages, because of women s increased risk of stroke with age; the risks of stroke associated with pregnancy, gestational hypertension, and hor- monal contraception; and the onset of stroke risk factors such as obesity, hypertension, and diabetes mellitus, which occur at younger ages. Future research focused on risk profile devel- opment is urgently needed to appropriately tailor prevention strategies for women. There is a need for recognition of wom- en s unique sex-specific stroke risk factors, and a risk score that includes these factors would thereby identify women at risk. Until sex-specific risk is better understood, prevention and management of stroke and cardiovascular risk factors remains essentially the same for men and women. Disclosures Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Cheryl Bushnell Wake Forest School of Medicine NIH/NINDS World Federation of Neurology None None None None None Louise D. McCullough University of Connecticut NIH/NINDS None Genentech* None None None None Issam A. Awad University of Chicago NIH/NINDS None None None None None None Monique V. Chireau Duke University Medical Center None None None None None None None Wende N. Fedder Alexian Brothers Health System None None None None None None None Karen L. Furie The Warren Alpert Medical School of Brown University/ Lifespan AHA ; NINDS None None None None UpToDate* JNNP Deputy Editor ; Stroke Vice Editor Virginia J. Howard University of Alabama at Birmingham NIH None None None None Spouse has relationship with Abbott Vascular*; spouse has relationship with Bayer* None Judith H. Lichtman Yale University AHA ; NINDS None None None None None None Lynda D. Lisabeth University of Michigan NIH None None None None None None Ileana L. Pi a Montefiore Medical Center None None None None None None None Mathew J. Reeves Michigan State University None None None None None None None Kathryn M. Rexrode Brigham and Women s Hospital NIH/NHLBI None None None None None None Gustavo Saposnik University of Toronto None None None None None Bayer* None Vineeta Singh University of California, San Francisco None None None None None None None Amytis Towfighi University of Southern California; Rancho Los Amigos National Rehabilitation Center AHA ; NIH/ NINDS None Boehringer Ingelheim* None None None None Viola Vaccarino Emory University None None None None None None None Matthew R. Walters University of Glasgow AstraZeneca*; GlaxoSmithKline*; Lundbeck*; Menarini*; Microtransponder, Inc*; Roche* None None None None Bayer*; Lundbeck*; UCB Pharma* None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be significant if (1) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Bushnell et al Guidelines for Prevention of Stroke in Women 1577 References 1. 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