Stroke in Women: Epidemiology, Risk, and Prevention Dr. Cheryl Bushnell

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1 Stroke in Women: Cheryl Bushne ll, MD, MHS Associate Professor of Neurology Wake Forest University Health Sciences Overview Epidemiology of stro ke: gender differences Risk and prevention issue s specific to women Risk screening recommendations 2 Female/male stroke prevalence ratios: REGARDS study F/M prev alence ratio Female/male stroke prevalence ratios: 1.5 REGARDS study Age Black White Howard VJ et al., The reasons for geographic and racial differences in stroke (REGARDS) study: Objectives and design. Neuroepidemiology. 2005; 25: The screen versions of these slides ha ve full details of copyright and acknowledgements 1

2 Mid-life stroke prevalence: increasing in women more than men Age group (yrs) Women Men OR (95% CI) P value Mid-life stroke prevalence: 1.2% 1.0% 1.21 ( ) increasing in women more than men % 1.0% 2.39 ( ) % 3.0% 1.13 ( ) 0.70 Towfighi et al., Neurology 2007;69:doi /01.wnl c2 4 Lifetime risk of stroke Seshadri et al., Stroke 2006; 37: Burden of stroke in women 20% lifetime prevalence of stro ke in women vs. 17% in men In 2000, there was an excess of 32,000 stro ke deaths in women By the year 2050: An excess of 68,000 stro ke deaths in women 198,000 stro ke events in white women vs. 129,000 in men 6 The screen versions of these slides ha ve full details of copyright and acknowledgements 2

3 Sex differences in stroke outcomes Women and men have similar stro ke severity However, women have: Poorer functional status (ADL s) Lower quality of life More disability More depression Less social support A higher likelihood of institutionalization than men Gray et al., Stroke 2007; 38: and Gargano, et al. Stroke 2007; 38: Comorbidities and stroke outcome in women mrs = Modified Rankin score 0 = no disability 1 = slight disability Comorbidities and stroke outcome in women 2 = mild disability 3 = moderate disability 4 = moderate to severe disability Bushnell et al., Stroke 2008; in press 8 Per 100,000 population Coronary heart disease Stroke Lung cancer Breast cancer White females Black females Age- adju sted d eath rat es fo r coron ary heart disease, stro ke, and lu ng an d b reast can cer fo r whit e and b lack females (United Stat es: 2004) Source: NCHS and NHLBI 9 The screen versions of these slides ha ve full details of copyright and acknowledgements 3

4 10 Epidemiology of stroke in women Excess burden of atrial fibrillation and hypertension 11 Sex-specific differences in risk factors 80 Barcelona, Spain 60 % Htn Afib IHD Diabetes PAD Smoking Alcohol Women Men Roquer Stroke 2003; 34: 1581 Risk factor 12 The screen versions of these slides ha ve full details of copyright and acknowledgements 4

5 Sex-specific differences in risk factors 60 European concerted action 40 % 20 0 Htn Afib IHD Diabetes Women Men Risk factor Di Carlo et al., Stroke 2003; 34: Sex-specific differences in risk factors Ontario, Canada % Htn Afib IHD Diab etes Women Men Holroyd-Leduc et al., Stroke; 31: 1833 Risk factor 14 Epidemiology of stroke in women Awareness of cardiov ascular disease 15 The screen versions of these slides ha ve full details of copyright and acknowledgements 5

6 Cardiovascular disease awareness in women % reporting leading cause of death Cardiovascular disease awareness in women Heart disease/ heart attack cancer Breast cancer other Christian et al., J Women s Health 2007; 16: doi: /jwh.2006.M Stroke symptom awareness Christian et al., J Women s Health 2007; 16: doi: /jwh.2006.M Cardiovascular awareness in women 23% of women felt uninformed about stro ke compared to 11% uninformed about heart disease African American women were more likely to report breast cancer as the greatest health problem in women Hispanic women: more likely to report there is nothing they can do to prevent CVD > 50% of women reported confusion related to basic CVD prevention strategies Christian et al., J Women s Health 2007; 16: doi: /jwh.2006.M The screen versions of these slides ha ve full details of copyright and acknowledgements 6

7 Cardiovascular prevention in women High risk, at risk, and optimal risk Lifestyle interventions Moderate intensity exercise for 30 minutes almost daily Cardiovascular prevention in women BMI < 25 kg/m 2 Rehabilitation (cardiac and stro ke) Recognize and treat depression Aspirin for high risk women and at risk women of any age if benefit outweighs adverse effects Mosca et al., Circulation 2007; 115: Epidemiology of stroke in women Stroke evaluation and treatment 20 Sex differences in diagnostic evaluation Smith et al., Neurology 2005; 65: The screen versions of these slides ha ve full details of copyright and acknowledgements 7

8 Women have better outcomes after tpa Probability of mrs <= 1 Men Kent et al., Stroke 2005; 36: Women tpa= tissue plasminogen activator 22 Risk and prevention issues specific to women Oral contraceptives Pregnancy and preeclampsia Menopause Hormone replacement 23 OCs and stroke risk: meta-analyses Author Pub lication years Estrog en t yp e Contro ls Odd s ratio s ( 95% CI) Gillu m Chan Lo w or h igh dose Lo w or h igh dose Hospit al and communit y Hospit al and communit y Current u se: 2.75 ( ) OCs and stroke risk: meta-analyses Lo w do se: 1.93 ( ) Cohort st udies: 0.95 ( ) Case cont rol: 2.13 ( ) Gillum et al., JAMA 2000; 284: 72 and Chan, et al. Arch Intern Med 2004; 164: The screen versions of these slides ha ve full details of copyright and acknowledgements 8

9 OCs and stroke: RATIO study Kemmeren et al., Stroke 2002; 33: Risk and prevention issues specific to women Oral contraceptives Pregnancy and preeclampsia Menopause Hormone replacement The screen versions of these slides ha ve full details of copyright and acknowledgements 9

10 Stroke-related pregnancy incidence Stro ke t yp e Ischemic stroke Intracranial hemorrhage Rat e/100,000 deliv eries Cereb ral v eno us thrombo sis 0.6 Pregnancy-relat ed CVE 15.9 CVE = Cerebrovascular event James et al., Obstet Gyn 2005; 106: Risk factors for peripartum stroke Odds ratio James et al., Obstet Gyn 2005; 106: Htn Heart dz 16 Throm bo SCD 9.1 SLE Migraine 4.4 Preeclampsia 29 Women s health study Multiv ariable adjusted relativ e hazard for ischemic stroke according to migraine status, stratified by age Migraine Non e N 83 Age <55 HR (95% CI) 1.00 N 169 Age >55 HR ( 95% CI) 1.00 Total ( ) ( ) W ith aura ( ) ( ) W ithout aura ( ) ( ) Kurth et al., Neurology 2005; 64: The screen versions of these slides ha ve full details of copyright and acknowledgements 10

11 Peripartum migraines: multivariable model Variable Age Preeclampsia Stroke VTE or PE MI or heart disease Hypertension Smoking Diabetes Bushnell et al., under review OR (95% CI) 1.03 (1.02, 1.03) 2.29 (2.13, 2.46) (8.26, 27.4) 3.23 (2.06, 7.07) 2.11 (1.76, 2.54) 8.61 (6.43, 11.54) 2.85 (2.53, 3.21) 1.96 (1.64, 2.35) P value < < < < < < < < Risk factors for pregnancy-related ICH Bateman et al., Neurology 2006; 67: Preeclampsia and stroke risk Duke perinatal and health services outcomes database Case-control study of 42,000 women Case s n = 164, controls n = 311 Preeclampsia (OR 2.06, 95% CI ) Gestational diabetes (OR 2.44, 95% CI ) Chireau, Bushnell et al., Ann Neurol 2005; 58 (Suppl 9): S41 Abstract 33 The screen versions of these slides ha ve full details of copyright and acknowledgements 11

12 Preeclampsia and stroke risk Stroke prevention in young women study Case s n = 261, controls n = 421 Preeclampsia 15% in cases, 10% in controls Ischemic stro ke OR 1.59 ( ) Brown, Dueker et al., Stroke 2006; 37: Preeclampsia and stroke risk Brown, Dueker et al., Stroke 2006; 37: Preeclampsia and stroke Possible explanations: Increased risk for hypertension Ongoing endothelial dysfunction Shared pathophysiology with atherosclerosi s Earliest sign of vascular disease 36 The screen versions of these slides ha ve full details of copyright and acknowledgements 12

13 Risk and prevention issues specific to women Oral contraceptives Pregnancy and preeclampsia Menopause Hormone replacement 37 Menopause and stroke risk Menopausal metabolic syndrome (theory) 1 Estrogen deficiency leads to: Increase in insulin resistance Worsening lipid profile Change in body fat distribution (increased visceral fat) Increased blood pressure 2 1. Spencer et al., Gynecol Endocrinol 1997; 11: Matthews et al., Stroke Menopause and stroke risk Subclinical atherosclerosis Carotid artery intimal medial thickness and prev alence of plaque post-menopause Sutton-Tyrrell et al., Stroke 1998; 29: Prabhakaran et al., Stroke 2006; 37: The screen versions of these slides ha ve full details of copyright and acknowledgements 13

14 Risk and prevention issues specific to women Oral contraceptives Pregnancy and preeclampsia Menopause Hormone replacement 40 Effects of HT on risk for CHD and stroke Coronary heart disease Stroke 1 prev ention 2 prev ention Time, y Time, y Time, y Summary: women and stroke Women are at a greater lifetime risk of stro ke Women have unique risks that include pregnancy, oral contraceptives, menopause, and hormone replacement Awareness of stro ke needs to be improved through educational efforts Poor outcomes in women after stroke can be avoided with early recognition and treatment with tpa and better prevention screening strategies 42 The screen versions of these slides ha ve full details of copyright and acknowledgements 14

15 Screening strategies In child-bearing women: Cardiovascular risk a sse ssment for women before prescribing OCs Ask about pregnancy complications such a s preeclampsia and gestational diabetes Screen for migraine headaches with aura 43 Screening strategies, cont. In women past child-bearing: Screen for hypertension soon after pregnancy in women with a history of gestational hypertension or preeclampsia Do not recommend hormone therapy more than 5 yrs post-menopause, especially if risk factors already present 44 Future directions More research to identify women at risk for stro ke at young ages Increase awareness in high risk groups Screening for subclinical disease needs to be tested for efficacy in preventing stroke s Strategies to improve adherence to proven prevention medications, especially for primary prevention 45 The screen versions of these slides ha ve full details of copyright and acknowledgements 15

16 Acknowledgements Colleagues: Larry Goldstein, MD Mathew Reeves, PhD George Howard, PhD HRT and stro ke seve rity participants Renetha Link, research nurse The screen versions of these slides ha ve full details of copyright and acknowledgements 16