Sex Differences in Stroke Risk and Quality of Life after Stroke

Transcription

1 Sex Differences in Stroke Risk and Quality of Life after Stroke Cheryl Bushnell, MD, MHS Associate Professor of Neurology Director, WFB Stroke Center

2 Disclosures Research funding from: World Federation of Neurology and the World Stroke Organization American Heart Association Patient Centered Outcomes Research Institute

3 Objectives To discuss the evidence for sex and gender differences in: Epidemiology Stroke risk factors unique to, or more prevalent in, women than men Quality of life after stroke

4 What are the sex differences in stroke? Men have a higher stroke incidence than women But, women have a 20% lifetime prevalence of stroke vs. 17% in men 1 About 30,000 more women die from stroke than men 2 Stroke is the 5 th leading cause of death in men but 3 rd leading cause in women 3 There are 200,000 more disabled women from stroke than men 4 1) Seshadri, et al. Stroke 2006;37: ) Lloyd-Jones D, Adams R, Carnethon M, et al. Circulation 2009:119e-e181. 3) National Center for Health Statistics US Department of Health and Human Services 4) Kelly-Hayes, et al. J Stroke Cerebrovasc Dis 2003

5 Women have different stroke symptoms at onset than men Women are more likely to have Pain Change in level of consciousness Non-specific symptoms LaBiche, et al. Annals of Emerg Med 2002

6 Gender differences in decision making In a hypothetical scenario involving acute and preventive stroke treatment: Women are less likely to choose IV tpa than men; adjusted OR 0.58 (95% CI, ) No difference in choosing carotid endarterectomy; adjusted OR 0.94 (95% CI, ) Kapral, et al. Medical Care 2006;44:70-80

7 Sex and Eligibility for IV tpa Study of exclusions for IV tpa by sex Eligibility for tpa was similar in men (6.8%) and women (6.1%; p=0.32 after adjustment for age) Women more likely to have severe hypertension (SBP >185 or DBP> 110) and have 2 (age and NIHSS) of the 5 ECASS III exclusions for hour window Women were not MORE likely to be treated than men Madsen, et al. Stroke 2015;46:717-21

8 Stroke risk scores Are sex differences adequately assessed?

9 Age Risk factors for stroke Men and Women Hypertension* Prior stroke/tias Diabetes Tobacco use Atrial fibrillation* Prior cardiovascular dz Hyperlipidemia Diet/Physical inactivity Depression and psychosocial stress* Unique to or more Prevalent in Women Oral contraceptives Hormone replacement Pregnancy/Preeclampsia Gestational diabetes Migraines with aura *More common in women than men

10 Stroke guideline Risk factors that are not included in the current stroke risk profile: Women younger than age 54 Oral Contraceptive (OC) use, migraines with aura, hx of preeclampsia, other pregnancy outcomes

11 Stroke in Pregnancy and Pregnancy Complications

12 Pregnancy Increases Risk of Stroke Increased risk during pregnancy and postpartum period (6-12 weeks after delivery) -occurs in about 34 per 100,000 pregnancies -21 per 100,000 non-pregnant women James, et al Obstet Gynecol

13 Preeclampsia/Eclampsia Of women with complications from preeclampsia/eclampsia, the cause of death in nearly 40% was a cerebrovascular event Definition New onset hypertension (>140/90 mmhg) after 20 weeks gestation And Proteinuria of >300 mg/24 h)

14 Definition of severe preeclampsia BP > 160/110 mmhg 2 measurements 4 hours apart) Thrombocytopenia (<100,000) Impaired liver function or severe persistent RUQ or epigastric pain unresponsive to pain medications or both Progressive renal insufficiency (Cr > 1.1 or doubling of Cr) Pulmonary edema New onset cerebral or visual disturbances Hypertension in Pregnancy ACOG 2013

15 Neurologic symptoms of preeclampsia Headache plus Confusion Visual deficits (including cortical blindness) Hyperreflexia and/or clonus Hemiparesis or other focal signs equals Severe preeclampsia and emergent delivery

16 Vasculopathies associated with preeclampsia/eclampsia Reversible Cerebral Vasoconstriction Syndrome (RCVS) Diffuse or multifocal segmental narrowing in the cerebral vessels (vasoconstriction) Decreased blood flow leads to cytotoxic edema, ischemia, and infarction Zeeman. Sem Perinatology 2009;33:166-72

17 Vasculopathies associated with preeclampsia/eclampsia Posterior Reversible Encephalopathy Syndrome (PRES) Sudden elevations in blood pressure exceed the cerebrovascular autoregulatory capacity Endothelial leakage and vasogenic edema Zeeman. Sem Perinatology 2009;33:166-72

18 Case #1 Healthy 24 yo woman, G1P0 Delivered a healthy baby boy in 2011 by Cesarean section 12 days after delivery, she developed high blood pressure, blurred vision and right leg weakness, seizure MRI brain showed 2 separate hemorrhages, evidence of severe hypertension She had ongoing partial seizures, now treated

19 Case #1 Imaging MRI brain showed 2 separate hemorrhages, Wake FLAIR Forest School of Medicine changes suggestive of PRES

20 Risk factors and treatment issues for a woman with hx of eclampsia What kind of oral contraceptives are safe? What is the risk of preeclampsia/eclampsia with subsequent pregnancies? What is the risk of developing other risk factors, such as hypertension? What is her risk of stroke later in life?

21 Preeclampsia and risk of future stroke Bellamy, et al. BMJ 2007; doi: /bmj

22 Preeclampsia may be first sign of vascular risk in women Bushnell and Chireau. Stroke Res Treat 2011;2011:858134

23 Recommendations: Treatment of HTN in Pregnancy and Postpartum Prevention of Stroke in Women with a History of Preeclampsia Class IIa Recommendations Because of the increased risk of future hypertension and stroke one to 30 years after delivery in women with a history of preeclampsia (Level of Evidence B) it is reasonable to (1) consider evaluating all women starting 6 months to the one 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. Class, (LOE) Class IIa, LOE C Bushnell, et al. Stroke 2014;Feb 6

24 Oral contraceptives

25 Oral contraceptive use: the landscape How many women use OCs? 10.7 million women aged15-44 years What is the incidence of stroke in this age group? (Lidegaard NEJM 2012) Ages 15-19: 3.4/100,000 Ages 45-49: 64.4/100,000

26 Oral contraceptives and ischemic stroke relative risk Population-based analysis in Denmark (Lidegaard, NEJM 2012) No risk with progestin-only formulations (IUD or pills) Other formulations: Adjusted RR 2.49 ( ) with vaginal ring RR 2.08 ( ) with transdermal patch Lidegaard, et al. NEJM 2012

27 Lidegaard, et al. NEJM 2012

28 OCs and stroke: RATIO study Kemmeren, et al. Stroke 2002;33:1202

29 Class I Recommendations: Oral Contraceptives Class I Recommendations Measurement of blood pressure prior to initiation of hormonal contraception is recommended. Class, (LOE) Class I, LOE B Bushnell, et al. Stroke 2014;Feb 6

30 Class III Recommendations: Oral Contraceptives Class III Recommendations OCs may be harmful in women with additional risk factors (e.g. cigarette smoking, prior thromboembolic events). Class, (LOE) Class III, LOE B Bushnell, et al. Stroke 2014;Feb 6

31 Class IIb Recommendations: Oral Contraceptives Class IIb Recommendations Class, (LOE) Among OC users, aggressive therapy for stroke risk factors may be reasonable. Class I, LOE C Bushnell, et al. Stroke 2014;Feb 6 31

32 Sex and gender differences in outcomes Disability and quality of life

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34 Results: Gender comparison Characteristic Overall (n=1370) Female (n=634) Male (n=736) P value Age, yrs, median (IQR) 65.0 ( ) 67.0 ( ) 64.0 ( ) <0.002 Race-ethnicity, n (%) White Black Hispanic Education, n (%) < High school Some college or higher Income adequate, n (%) 1143 (83.4) 147 (10.7) 34 (2.5) 725 (52.9) 625 (45.6) 524 (82.6) 79 (12.5) 14 (2.2) 357 (56.3) 269 (42.4) 619 (84.1) 68 (9.2) 20 (2.7) 368 (50.0) 356 (48.4) Yes 984 (71.8) 449 (70.8) 535 (72.7) Married, n (%) 838 (61.2) 323 (51.0) 515 (70.0) <.001 Living situation With someone, home Alone At institution Work status, n (%) Home not by choice Home by choice Working 1045 (76.3) 312 (22.8) 8 (0.6) 143 (10.4) 634 (46.3) 585 (42.7) 443 (69.9) 184 (29.0) 7 (1.1) 71 (11.2) 348 (54.9) 215 (33.9) 602 (81.8) 128 (17.4) 1 (0.1) 72 (9.8) 286 (38.9) 370 (50.3) <.001 <.001

35 Results: Gender comparison Characteristic Overall (n=1370) Female (n=634) Male (n=736) P value Previous stroke/tia 286 (23.0) 141 (24.6) 145 (21.7) CAD/Prior MI 300 (24.2) 100 (17.5) 200 (29.9) <.001 Atrial fibrillation/flutter 134 (10.8) 65 (11.4) 69 (10.3) Diabetes 346 (27.9) 149 (26.0) 197 (29.4) Hypertension 983 (79.2) 455 (79.6) 528 (78.9) Smoker 306 (24.7) 128 (22.4) 178 (26.6) Dyslipidemia 603 (48.6) 260 (45.4) 343 (51.3) # Meds at discharge, median (IQR) 6.0 (4-9) 6.0 (4-9) 6.0 (4-8) 0.008

36 Results: Outcomes at 3 and 12 mos Outcome Overall Female Male P value 3 months mrs > 3, n (%) 293 (21.4) 170 (26.8) 123 (16.7) <.001 mrs < (78.3) 462 (72.9) 611 (83.02) PHQ-8, median (IQR) 3.0 (1-7) 4.0 (1-8) 3.0 (1-7) <.001 EQ5D, median (IQR) 0.83( ) 0.81( ) 0.84( ) < months mrs > 3, n (%) 284 (20.7) 162 (25.6) 122 (16.7) <.001 mrs < (79.2) 471 (74.3) 614 (83.4) PHQ-8, median (IQR) 3.0 (0-7) 4.0 (1-8) 3.0 (0-6) <.001 EQ5D, median (IQR) 0.83 ( ( ) 0.84 ( ) < ) All-cause rehosp., d/c to 12 mo, n (%) 286 (20.9) 144 (22.7) 142 (19.3) 0.123

37 % No Problems 3-month EQ5D and gender by domain Mobility* Self-care Usual activ* Pain/discomf* Anx/depress* EQ5D Domain Women Men * Indicates p<0.007

38 % No Problems 12-month EQ5D and gender by domain Mobility* Self-care Usual act Pain/discomf* Anx/Depress* * Indicates p<0.007 EQ5D Domain Women Men

39 Mean difference 3-month mean difference in EQ5D: women vs men Unadjusted Model 2 Model 3 Model Model 2: Gender, age, race, marital status Model 3: Model 2 plus education, baseline living and work status*, adequate income*, and insurance Model 4: Model 3 plus stroke vs TIA, # risk factors, # meds prescribed at discharge*, and NIHSS* * Indicates p<0.007 in model 4

40 Gender difference in self-report of stroke recovery: Northern Manhattan Study Have you made a full recovery? Do you need help? Women in the highest functional recovery category reported less recovery and a greater need for help than men in the same category Depression was associated with need for help in women Chong, et al. Neurology 2006:67:1282-4

41 Rehabilitation: Sex differences 440 men and women with stroke in Rome, Italy, matched for severity, age, and onset-admission interval within 3 days Men had 3-fold higher odds of independence with stair-climbing Women had 1.7-fold higher odds of walking with cane or aid Paolucci, et al. Stroke 2006;37:

42 Sex and Gender Gap Summary and Future Directions Stroke risk and outcomes differ in men and women Stroke risk scores should be re-evaluated with risks unique to women Worse outcomes in women are not entirely explained by older age and prestroke co-morbidity More research is needed to understand the biology of sex differences in stroke risk and outcomes

43 Thank you!