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1 Sex Disparities i Stroke: Wome Have More Severe Strokes but Better Survival Tha Me Christia Dehledorff, MS, PhD; Klaus Kaae Aderse, MS, PhD; Tom Skyhøj Olse, MD, PhD Backgroud- Ucertaity remais about whether stroke affects me ad wome similarly. We studied differeces betwee me ad wome with regard to stroke severity ad survival. Methods ad Results- We used the Daish Stroke Registry, with iformatio o all hospital admissios for stroke i Demark betwee 2003 ad 2012 (N=79 617), ad the Daish Register of Causes of Death. Iformatio was available o age, sex, marital status, stroke severity, stroke subtype, socioecoomic status, ad cardiovascular risk profile. We studied oly deaths due to the idex stroke, with the assumptio that death reported o death certificates as due to stroke was related to the idex stroke if death occurred withi the first week or moth after stroke. Multivariate Cox regressio aalysis ad multiple imputatio were applied. Stroke was the cause of death for 4373 ad 5512 of the patiets withi 1 week (5.5%) or 1 moth (6.9%), respectively. After the age of 60 years, wome had more severe strokes tha me. Up to ages i the mid-60s, o differece i the risk of death from stroke was see betwee the 2 sexes. For people aged >65 years, however, the risk gradually became greater i me tha i wome ad sigificatly so (>15%) from the mid-70s (adjusted for age, marital status, stroke severity, stroke subtype, socioecoomic status, ad cardiovascular risk factors). Results were essetially the same whe aalyzig deaths withi 1 week, 1 moth ad ischemic ad hemorrhagic stroke separately. Coclusios- Stroke affects wome ad me differetly. Elderly wome were affected more severely tha elderly me but were more likely to survive. ( J Am Heart Assoc. 2015;4:e doi: /JAHA ) Key Words: mortality sex stroke stroke severity survival Iformatio about whether a give treatmet works i the same way for me ad wome is essetial. This kowledge requires studies of whether me ad wome are affected by the same disease i the same way ad whether their survival after the disease is the same. Stroke is the secod leadig cause of death ad the secod largest burde of disease i the Wester world 1 ; therefore, treatmets that ca mitigate the cosequeces of stroke are essetial. Noetheless, ucertaity exists about how stroke affects the 2 sexes i terms of survival ad severity. I some studies, the ability to survive was urelated to sex, whereas i others, survival was either better or worse i wome tha i me. 2 4 Similar From the Sectio of Statistics, Daish Cacer Society Research Ceter, Copehage, Demark (C.D., K.K.A.); Departmet of Neurology, Bispebjerg Uiversity Hospital, Copehage, Demark (T.S.O.). Correspodece to: Tom Skyhøj Olse, MD, PhD, Departmet of Neurology, DK-2400 Copehage NV, Demark. tso@dadlet.dk Received February 25, 2015; accepted Jue 8, ª 2015 The Authors. Published o behalf of the America Heart Associatio, Ic., by Wiley Blackwell. This is a ope access article uder the terms of the Creative Commos Attributio-NoCommercial Licese, which permits use, distributio ad reproductio i ay medium, provided the origial work is properly cited ad is ot used for commercial purposes. ucertaity is see i studies of stroke severity i me ad wome. 4,5 Kowledge about the severity of the stroke leadig to death is a prerequisite for studies of survival after stroke. The available studies of me s ad wome s abilities to survive stroke have icluded ot oly death due to the idex stroke but also death due to other diseases (eg, recurret stroke, heart disease, cacer, ifectio) for which there was o iformatio o severity If wome have strokes of differet severity from those of me, studies of male ad female survival after stroke are at risk for selectio bias uless the severity of the stroke from which the patiet dies is kow. I additio to iformatio o stroke severity, such studies also require certaity that the death resulted from the idex stroke. No studies have bee performed i which these precoditios were fulfilled, ad that may explai the widely diverget reports of me s ad wome s chaces of survival after stroke. The purpose of this ivestigatio was to study potetial sex disparities i stroke by comparig me s ad wome s abilities to survive after stroke, with adjustmet for differeces i demographics, socioecoomic status, cardiovascular risk factor profile, stroke subtype, ad severity of the idex stroke i patiets admitted to Daish hospitals for DOI: /JAHA Joural of the America Heart Associatio 1

2 stroke betwee 2003 ad To avoid selectio bias, we studied oly deaths due to the idex stroke, with the assumptio that a death due to stroke as recorded o death certificates was due to the idex stroke if the death occurred withi the first moth after the stroke. Material ad Methods The study is based o data i the Daish Stroke Registry (formerly the Daish Natioal Idicator Project), which is described i detail elsewhere. 10,12 The registry cotais iformatio o all hospital admissios for stroke i Demark; coverage is curretly estimated (by professioal cosesus) to be >80%. 13 All Daish hospitals report a defied set of data o all patiets admitted for acute stroke, icludig age, sex, marital status, admissio stroke severity measured o the Scadiavia Stroke Scale, 14 stroke subtype (ischemic or hemorrhagic), ad a predefied cardiovascular profile. The Scadiavia Stroke Scale is a validated eurological scale for evaluatig level of cosciousess; eye movemet; power i the arm, had, ad leg; orietatio; aphasia; facial paresis; ad gait, with a total score of 0 to 58. Lower scores idicate more severe stroke. Ischemic stroke was distiguished from primary itracerebral hematoma by computed tomography or magetic resoace scaig. The cardiovascular profile icluded iformatio o alcohol cosumptio (high: >14 driks per week for wome ad >21 for me; low to moderate: 14 driks per week for wome ad 21 for me), smokig (curret daily smoker, former smoker, ever smoker), diabetes mellitus, atrial fibrillatio (chroic or paroxysmal), arterial hypertesio, previous myocardial ifarct, previous stroke, itermittet arterial claudicatio, ad body mass idex. Diabetes mellitus, atrial fibrillatio, arterial hypertesio, previous myocardial ifarct, ad previous stroke were diagosed accordig to curret Daish stadards 12 ad were either kow before the oset of stroke or diagosed durig hospitalizatio. Body mass idex was divided ito 4 categories (i kg/m 2 ): uderweight (<20), ormal weight (20 to 25), overweight (25 to 30), ad obese (>30). Stroke was defied accordig to World Health Orgaizatio criteria. 15 Patiets with subarachoid hemorrhage were excluded from the study, as were patiets with trasiet ischemic attacks. For patiets with multiple evets, oly the first evet was icluded i the aalysis. We excluded patiets aged <19 years ad patiets i whom computed tomography or magetic resoace scaig had ot bee performed (0.9%) or was uavailable (0.9%). Time was scaled from the day of hospital admissio. For all patiets i the study populatio, we obtaied iformatio o level of educatio ad disposable icome by likage to the registries of Statistics Demark. 16 Educatio was grouped ito 4 categories: basic or high school, defied as 7 to 12 years of primary, secodary, ad grammar school educatio; vocatioal, defied as 10 to 12 years of educatio icludig vocatioal traiig; higher, defied as 13 years of educatio; ad ukow or missig. Disposable icome was defied as household icome after taxatio ad iterest per perso, adjusted for the umber of people i the household ad deflated accordig to the 2000 value of the Daish kroe ad categories accordig to quitiles i the geeral populatio. Survival was followed through the Daish Cetral Perso Registry. Cause of death was obtaied from the Daish Register of Causes of Death ad was divided ito 5 groups accordig to the Iteratioal Classificatio of Diseases, 10th revisio (ICD-10) 17 : stroke (I60 to I69), heart disease (I00 to I25, I27, I30 to I51), cacer (C00 to C97), respiratory disease (J00 to J99), ad other diseases. For the purpose of this study, we studied oly deaths declared as caused by stroke (ICD-10 codes I60 to I69) withi the first moth after the idex stroke. Separate aalyses were performed for all stroke, ischemic stroke, ad hemorrhagic stroke. Iclusio of patiets bega Jauary 1, 2003, ad the ed of follow-up was December 31, Follow-up withi the first moth after stroke was complete. The study was approved by the boards of the Daish Stroke Registry ad the Daish Data Protectio Agecy (joural umber ). Figure 1. Age-specific stroke severity i me ad wome after adjustmet for cardiovascular risk profile, icome, ad educatio ad multiple imputatio. For each sex, the mea severity as a fuctio of age is give with 95% poitwise cofidece limits. The iteractio betwee age ad sex is sigificat (P<0.0001), amely, the associatio betwee age ad severity is sigificatly differet for me ad wome. DOI: /JAHA Joural of the America Heart Associatio 2

3 Table. Cardiovascular Risk Factors, Stroke Subtype, Marital Status, ad Socioecoomic Status of the Participats by Sex Characteristics All Female Male Stroke* Stroke All Age, y 19 to to to to Marital status Sigle Not sigle No data Alcohol cosumptio Low to moderate High No data Smokig Never Ever No data Diabetes mellitus No Yes No data Atrial fibrillatio No Yes No data Previous myocardial ifarct No Yes No data Hypertesio No Yes No data Stroke type Hemotomas Ischemic Itermittet arterial claudicatio No Yes No data Stroke Cotiued DOI: /JAHA Joural of the America Heart Associatio 3

4 Table. Cotiued Characteristics Statistics All Female Male Stroke* Differeces i icome, educatio, ad cardiovascular risk profile betwee me ad wome were tested with v 2 tests after adjustmet for age ad stroke severity by iverse probability weightig. 18 We applied multiple liear regressio to describe differeces i stroke severity as a fuctio of age by separate restricted cubic splies for me ad wome, with adjustmet for cardiovascular risk profile, icome, educatio, ad marital status. I our data set, the probability of missig data was associated with stroke severity but, to our kowledge, ot Stroke Quitile of disposable icome No data Educatio Higher Vocatioal Ukow Basic Severity score 0 to to to to Body mass idex, kg/m 2 < to to > No data Previous stroke No Yes No data Stroke Age ad severity score are categorized i quartiles. *Deaths from stroke are deaths withi 1 moth of admissio. High alcohol cosumptio: >14 driks/week for wome ad 21 for me. Low to moderate alcohol cosumptio: 14 driks/week for wome ad 21 for me. with the variable itself. Cosequetly, we believed that data were missig at radom, ad thus we applied multiple imputatio (10 repetitios) i cases for which iformatio o ay of the variables of iterest was missig. We used Cox regressio models of the evet of death by stroke withi 1 week ad 1 moth by cesorig for death due to other causes, ed of follow-up, or loss to follow-up, whichever came first. Separate aalyses were performed for all stroke, ischemic stroke, ad hemorrhagic stroke. As a sesitivity aalysis, a additioal aalysis of all-cause mortality withi 1 week ad 1 moth was performed. We used time sice admissio as the uderlyig time scale, with adjustmet DOI: /JAHA Joural of the America Heart Associatio 4

5 Figure 2. Age-specific stroke severity i me ad wome with ischemic stroke after adjustmet for cardiovascular risk profile, icome, ad educatio ad multiple imputatio. For each sex, the mea severity as a fuctio of age is give with 95% poitwise cofidece limits. The iteractio betwee age ad sex is sigificat (P<0.0001), amely, the associatio betwee age ad severity is sigificatly differet for me ad wome. Figure 3. Age-specific stroke severity i me ad wome with hemorrhagic stroke after adjustmet for cardiovascular risk profile, icome, ad educatio ad multiple imputatio. For each sex, the mea severity as fuctio of age is give with 95% poitwise cofidece limits. The iteractio betwee age ad sex is isigificat (P=0.1032), amely, the associatio betwee age ad severity is ot sigificatly differet for me ad wome. for marital status, icome, educatio, ad cardiovascular risk profile. Stroke severity was categorized i quartiles, ad age was icluded as a cotiuous variable by meas of restricted cubic splies to accout for oliearity. For age, separate restricted cubic splies were estimated for me ad wome. We repeated the aalyses without adjustmet ad tested the cubic splies agaist liear alteratives by meas of likelihood ratio tests. The results are preseted graphically, amely, the estimated hazard ratio (HR; me versus wome) with 95% poitwise cofidece itervals as a fuctio of age, with a referece lie at a HR of 1 correspodig to equal hazard. Sigificat differeces i me versus wome ca be see from the cofidece itervals (ie, compared with the referece lie). Global tests of risk differeces betwee me ad wome were performed by likelihood ratio tests. I all aalyses, we applied multiple imputatio (10 repetitios) i cases for which iformatio was missig. We used R versio (R Foudatio) for all aalyses 19 ad accepted sigificace at 5%. Results Of the patiets with stroke registered i the Daish Stroke Registry, 47.2% were wome ad 91.7% had ischemic stroke. The mea age of the wome was 74.4 years (SD 13.6), ad the me had a mea age of 69.5 years (SD 12.5) (P<0.0001). The mea stroke severity score was 40.4 (SD 17.3) for wome ad 44.0 (SD 15.6) for me (P<0.0001). The severity of stroke icreased with age (Figure 1), with a accelerated icrease after 60 years. Overall, 96% of the patiets were treated i stroke uits. The cardiovascular risk factor profile, marital status, ad socioecoomic status of the patiets are listed i Table. Data were complete for >80% of all variables except body mass idex (70%); for patiets, there was complete iformatio o all variables. After adjustmet for age ad stroke severity by iverse probability weightig, me more ofte had diabetes mellitus, previous myocardial ifarct, itermittet arterial claudicatio, ischemic stroke, previous stroke, ad high alcohol cosumptio compared with wome. Wome more ofte had hypertesio ad atrial fibrillatio ad were less ofte obese. Me were also more ofte smokers, more ofte had higher educatio, ad more ofte had the highest quitile of icome. Age- ad sex-specific stroke severity (all stroke) adjusted for cardiovascular risk factors, stroke subtype, marital status, ad socioecoomic positio by multiple imputatio for all cases is show i Figure 1, which idicates that after the age of 60 years, wome had more severe strokes tha me, with the icrease beig sigificat amog those aged early 70s ad older. The same results were see whe aalyzig ischemic stroke (Figure 2) ad hemorrhagic stroke DOI: /JAHA Joural of the America Heart Associatio 5

6 Figure 4. Age-specific HRs of death by stroke (me vs wome), adjusted ad uadjusted for stroke severity, cardiovascular risk profile, icome, ad educatio ad with multiple imputatio after 1 week ad 1 moth. The solid lie is the HR, ad the dashed lies are 95% poitwise cofidece itervals. The horizotal lie at HR 1.0 correspods to the same hazard for me ad wome, ad thus statistical sigificace ca be judged by comparig the cofidece limits with this lie. Global tests for differeces betwee me ad wome i the adjusted aalyses give P= for 1 week ad P< for 1 moth. HR idicates hazard ratio. (Figure 3) separately, although results were isigificat for the latter. Of the patiets, 4373 (5.5%) died withi the first week of their stroke, ad stroke was give as the cause of death o the death certificates of 3334 (4.2%). Withi the first moth, 7878 patiets (9.9%) died, ad stroke was give as the cause of death o the death certificates of 5512 (6.9%). Cosequetly, stroke was the cause of death o death certificates i 76% of cases withi the first week ad i 70% of cases withi the first moth after stroke. The followig causes of death (other tha stroke) withi 1 week or 1 moth were oted: heart disease (535 or 1176 patiets), cacer (110 or 310 patiets), respiratory disease (68 or 172), ad other diseases (326 or 668 patiets). Figure 4 shows the sex-specific risk for death by all stroke withi 1 week ad 1 moth after the stroke, uadjusted ad adjusted for age, sex, stroke severity, stroke subtype, marital status, cardiovascular risk factors, duratio of educatio, ad icome. The uadjusted risk for death from stroke withi the first moth of hospital admissio was higher for wome tha for me aged 50 to 85 years, although it was isigificat; however, adjustmet for stroke severity, stroke subtype, civil status, cardiovascular risk factors, duratio of educatio, ad icome chaged this fidig. Me ad wome aged up to their mid-60s showed o differece i risk of death from stroke. After the age of 65 years, however, the risk for me gradually icreased beyod the risk for wome ad sigificatly so (>15%; lower cofidece limit >1) amog those i their mid- 70s (death withi 1 moth) ad mid-80s (death withi 1 week). The result of a aalysis based o all-cause death (stroke, heart disease, cacer, respiratory disease, other DOI: /JAHA Joural of the America Heart Associatio 6

7 diseases) was essetially the same (Figure 5). Separate aalyses for death by ischemic stroke (Figure 6) ad hemorrhagic stroke (Figure 7) revealed the same tred of a female survival advatage amog elderly stroke patiets, although the advatage was isigificat i some cases due to the lower statistical power i the stratified aalysis. Discussio Figure 5. Age-specific HRs of death by all causes (me vs wome), adjusted ad uadjusted for stroke severity, cardiovascular risk profile, icome, ad educatio ad with multiple imputatio after 1 week ad 1 moth. The solid lies are the HRs, ad the dashed lies are 95% poitwise cofidece itervals. The horizotal lie at HR 1.0 correspods to the same hazard for me ad wome, ad thus statistical sigificace ca be judged by comparig the cofidece limits with this lie. Global tests for differeces betwee me ad wome i the adjusted aalyses give P= for 1 week ad P< for 1 moth. HR idicates hazard ratio. This study demostrates sex disparities i stroke severity ad survival. Although little differece was see at youger ages, elderly wome were affected more severely tha me but were more likely to survive. Most studies have idicated that stroke is more severe i wome tha i me, although the fidig has bee regarded as a result of cofoudig by age. 5 As show i our study, wome are usually older tha me whe they have a stroke, ad severity icreases with age; however, eve after adjustmet for cardiovascular risk profile, socioecoomic status, ad age, stroke remaied more severe i wome. Severity is the most importat determiat of short-term survival after a stroke, 20 ad iformatio o this aspect is essetial for examiig sex differeces i mortality after stroke. I its absece, mortality amog wome will ievitably appear higher tha that amog me because stroke severity is liked directly to the risk of death after stroke. I studyig sex differeces i stroke survival, iformatio o stroke severity is useful oly if the deaths studied are due to a idex stroke for which iformatio o severity is available. If death is due to diseases other tha the idex stroke ad o iformatio o severity before death is DOI: /JAHA Joural of the America Heart Associatio 7

8 Figure 6. Age-specific HRs of death by stroke (me vs wome), adjusted ad uadjusted for stroke severity, cardiovascular risk profile, icome, ad educatio ad with multiple imputatio after 1 week ad 1 moth (ischemic strokes). The solid lies are the HRs, ad the dashed lies are 95% poitwise cofidece itervals. The horizotal lie at HR 1.0 correspods to the same hazard for me ad wome, ad thus statistical sigificace ca be judged by comparig the cofidece limits with this lie. Global tests for differeces betwee me ad wome i the adjusted aalyses give P= for 1 week ad P= for 1 moth. HR idicates hazard ratio. available, iformatio o the severity of the idex stroke is of o value because the death was ot ecessarily due to the idex stroke. I our study, oe-third of deaths withi the first moth after a stroke were due to diseases other tha the idex stroke. Iformatio o stroke severity was ot available i may studies of sex differeces i stroke survival. 21 Because stroke is geerally more severe i wome, these studies were subject to selectio bias ad gave the impressio that the survival of wome was poorer tha that of me. Studies i which iformatio o stroke severity was available 7 11 also icluded deaths due to ay cause, thereby itroducig potetial bias because me s ad wome s survival capacity was compared i the absece of iformatio o the severity of the diseases leadig to death for large umbers of patiets (i our study, oe-third of the populatio). To the best of our kowledge, we are the first to study sex differeces i death due to a idex stroke with iformatio o the severity of the disease leadig to death (i this case, the idex stroke) for all cases. I this way, we obviated potetial bias. Our study gives o explaatio of differece i survival or severity of stroke betwee me ad wome. The size of stroke lesios (ifarcts or hematomas) relative to brai volume may differ betwee me ad wome, but we had o iformatio o this factor. Cliically, wome may respod differetly from me to the same brai lesio. There is ow strog evidece of sexual dimorphism i stroke, with differeces observed both cliically ad i the laboratory. 22 Wome suffer greater stroke-related disability ad poorer quality of life tha me after stroke. 3,4 Experimetally, ischemiaiduced cell death pathways differ betwee the 2 sexes. 23 I vivo models of ischemic stroke have show smaller ifarcts DOI: /JAHA Joural of the America Heart Associatio 8

9 Figure 7. Age-specific HRs of death by stroke (me vs wome), adjusted ad uadjusted for stroke severity, cardiovascular risk profile, icome, ad educatio ad with multiple imputatio after 1 week ad 1 moth (hemorrhagic stroke). The solid lies are the HRs, ad the dashed lies are 95% poitwise cofidece itervals. The horizotal lie at HR 1.0 correspods to the same hazard for me ad wome, ad thus statistical sigificace ca be judged by comparig the cofidece limits with this lie. Global tests for differeces betwee me ad wome i the adjusted aalyses give P= for 1 week ad P= for 1 moth. HR idicates hazard ratio. i youger wome ad larger ifarcts with age compared with me. 24 The heavier load of cardiovascular risk factors associated with male sex caot explai the female survival advatage because we adjusted for sex differeces i the cardiovascular risk factor profile. The differece i survival betwee me ad wome was see aroud the age of 65 years ad appeared to icrease with age. Although this coclusio is speculative, the differece could be a result of the progressive decrease i testosteroe i elderly me. New evidece idicates that low adroge levels are associated with death from all causes, i particular from cardiovascular disease. 25,26 Testosteroe is associated with may factors that might ifluece vital fuctios ad processes i the acute state of stroke, such as blood glucose, blood pressure, isuli resistace, lipids, iflammatory cytokies, ad vascular toe, 26 ad thus might ifluece survival i the acute stage of stroke. Our study had both stregths ad weakesses. Its stregth is its large sample size, which provided high statistical power. We icluded patiets without limitatio o age (>19 years), sex, or stroke severity. Stroke severity was measured o hospital admissio with a well-validated eurological scale. Data o survival up to 1 moth after a stroke, icludig causes of death recorded o death certificates, were complete, ad we studied oly deaths that were stated o death certificates as caused by stroke. I populatio-based studies, two-thirds of early deaths after stroke were reported to be due to the idex stroke, ad this fidig was corroborated i our study, i which 70% of deaths withi 1 moth of a stroke were due to stroke, as stated o death DOI: /JAHA Joural of the America Heart Associatio 9

10 certificates. Although useful i determiig cause of death, 30 death certificates are subject to some ucertaity. 31 I aother Scadiavia study, 32 reevaluatio of the accuracy of death certificates revealed disagreemet of 45% at the 4-digit ICD-10 level ad 12% to 13% at the 3-digit level (the ICD-10 level used i this study). The validity of causes of death accordig to death certificates should be see i this light. Because we limited our study to deaths occurrig i close relatio to the stroke icidet, withi 1 week ad 1 moth of the stroke, we cosider the deaths studied, for the most part, to be related to the idex stroke. Although ischemic ad hemorrhagic strokes carry differet mortality rates, especially i the acute stage, 33 the results of separate aalyses for ischemic ad hemorrhagic strokes were essetially the same as those of the aalysis of all strokes. Fially, the results of a sesitivity aalysis icludig death by all causes did ot deviate from those of the aalysis of death by stroke. Although the Daish Stroke Registry is a atiowide registry of all patiets admitted to the hospital for acute stroke, its coverage is ot yet complete (presetly estimated to be 80%). 13 The completeess of data o diabetes, previous myocardial ifarct, atrial fibrillatio, ad hypertesio was >95%, ad completeess for alcohol cosumptio, smokig, ad itermittet arterial claudicatio data was >78%. Treatmet would have bee uiform because 96% of patiets were treated i a stroke uit. Nevertheless, we applied multiple imputatio to compesate for missig iformatio. Whe we restricted the aalysis to the patiets for whom complete iformatio was available o all variables (data ot show), our coclusio remaied the same: Elderly wome were more likely to survive stroke tha elderly me. We caot exclude the possibility of bias due to variables (that might have iflueced survival) ot recorded i the registry; however, differeces i quality of treatmet betwee me ad wome ca hardly explai wome s survival advatage. A study based o stroke patiets i the Daish Stroke Registry observed o substatial sex-related differeces i the quality of acute hospital care i Demark, ad sex-related differeces i mortality appeared ot to be explaied by differeces i acute hospital care. 11 I coclusio, sex disparities i stroke are usually cosidered to be the result of cofoudig by age ad comorbidity before the stroke; however, this study provided evidece of iate sex-specific differeces. Strokes were more severe i wome; therefore, adjustmet for stroke severity is essetial whe studyig stroke outcomes. The excess mortality amog wome i the uadjusted aalysis was replaced by excess mortality amog me i their mid-60s ad older i our adjusted aalyses. Our study is the first with iformatio o the severity of stroke resultig i death, so the domiat determiats of death due to this cause (ie, age ad stroke severity) were take ito accout. Our results show a iate female superiority i likelyhood of survival after stroke. Both experimetal ad cliical research o stroke has bee coducted i populatios domiated by youg me, whereas most stroke patiets are elderly ad female, ad it was i this group of stroke patiets that sex differeces i stroke severity ad survival were see. A true picture of the cliical reality ca be see oly if more focus is directed to elderly patiets ad if outcomes are evaluated for each sex. Disclosures Noe. Refereces 1. Lopez AD, Mathers CD, Ezzati M, Jamiso DT, Murray CJL. Global ad regioal burde of disease ad risk factors, 2001: systematic aalysis of populatio health data. Lacet. 2006;367: Zhou G, Nie S, Dai L, Wag X, Fa W. Sex differeces i stroke case fatality: a meta-aalysis. Acta Neurol Scad. 2013;128: Bushell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, Howard VJ, Lichtma JH, Lisabeth LD, Pi~a IL, Reeves MJ, Rexrode KM, Saposik G, Sigh V, Towfighi A, Vaccario V, Walters MR. Guidelies for the prevetio of stroke i wome: a statemet for healthcare professioals from the America Heart Associatio/America Stroke Associatio. Stroke. 2014;45: Reeves MJ, Bushell CD, Howard G, Gargao JW, Duca PW, Lych G, Khatiwoda A, Lisabeth L. Sex differeces i stroke: epidemiology, cliical presetatio, medical care, ad outcomes. Lacet Neurol. 2008;7: Reeves MJ, Lisabeth LD. The cofoudig issue of sex ad stroke. Neurology. 2010;74: Di Carlo A, Lamassa M, Cosoli D, Valetia V, Izitari D. Sex differeces i presetatio, severity, ad maagemet of stroke i a populatio-based study. Neurology. 2010;75: Glader EL, Stegmayr B, Norrvig B, Teret A, Hulter-Asberg K, Wester PO, Asplud K. Sex differeces i maagemet ad outcome after stroke: a Swedish atioal perspective. Stroke. 2003;34: Labiche LA, Cha W, Saldi KR, Morgester LB. Sex ad acute stroke presetatio. A Emerg Med. 2002;40: Kapral MK, Fag J, Hill MD, Silver F, Richards J, Jaigobi C, Cheug AM. 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