Previous studies have shown that the agestandardized

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1 725,, ad Case-Fatality of Stroke i Norther Israel Leo Epstei, Shmuel Rishpo, Ephraim Betal, Gerald Brook, Ada Tamir, Bella Gross, Migel Szwarc, Judith Maelis, ad Thomas Pillar We studied the icidece ad mortality of stroke i orther Israel to determie possible reasos for the differeces previously foud i mortality from this coditio betwee the sex ad ethic groups i Israel as a whole. We idetified 1,149 cases of stroke durig While the age-stadardized icidece was higher i me, the case-fatality rate was twice as high i wome. After cotrollig for ethic origi, we foud that icidece was higher oly i me of Wester origi, while the female rates were higher i wome of Asia ad North Africa extractio. The case-fatality rate was substatially higher i wome i all ethic groups. These differeces, especially i relatio to the case-fatality rate, have importat implicatios for health services i relatio to both possible prevetive actio ad to maagemet of the acute disease phase. (Stroke 1989;20: ) Previous studies have show that the agestadardized mortality from stroke i Israel amog Jews is higher amog wome tha amog me. This fidig holds true for each of the three major ethic groups (those bor i Wester coutries, i Asia, or i North Africa 12 ) (Figure 1) ad is i cotrast to published data from most other coutries, i which mortality is higher amog me. I additio, there are clear differeces i mortality amog ethic groups i that both me ad wome of North Africa origi have the highest ad immigrats from Europe ad other Wester coutries the lowest rates, while the rates of those of Asia extractio fall betwee the two extremes. Whe cosiderig the reasos for these differeces i mortality, two possibilities eed to be take ito accout. Oe is the differece i icidece rate amog the three ethic groups; aother is the differece i case-fatality rates amog the ethic groups, which results i a mortality differetial eve whe the icidece is similar. Further- From the Departmet of Family ad Commuity Health, Faculty of Medicie, The Techio, Israel Istitute of Techology ad Kupat Holim, Health Isurace Istitute of the Geeral Federatio of Labour (L.E., S.R., A.T.), the Departmets of Neurology (E.B.) ad Iteral Medicie D (G.B.), Rambam Medical Ceter, the Departmets of Neurology, Carmel (B.G.), Rothschild (M.S.), ad Nahariya (J.M.) Hospitals, ad the Flima Geriatric Hospital (T.P.), Haifa, Israel. Supported by grats from the Chief Scietist's Office, Israel Miistry of Health ad from The Techio V.P.R. Fud, Hedso Fud for Medical Research, The Techio, Israel Istitute of Techology, Haifa, Israel (for the populatio data). Address for correspodece: Prof. Leo Epstei, Carmel Hospital, 7 Michal Street, Haifa 34362, Israel. Received February 5, 1988; accepted December 15, more, a combiatio of the two possibilities might well be operatig. I view of the importace of the differet mortality rates, both epidemiologically ad for the provisio of health services, we examied the possible uderlyig reasos as part of our study performed i the orther part of Israel. Subjects ad Methods The study populatio icluded all the cases of acute, otraumatic stroke that occurred amog Jews i the Haifa ad Acre subdistricts (the regio) i the orther part of Israel (populatio approximately 600,000) from Jauary 1, 1984, util December 31, (The Arab populatio of the regio was excluded from the study because of the icomplete ature of data o stroke morbidity i this ethic group.) The ethic origi of each perso idetified was defied by the coutry of birth of his or her father; Wester origi icluded all Europea coutries ad the US. The diagostic categories icluded were acute stroke, cerebral ifarctio, subarachoid hemorrhage, itracerebral hemorrhage, stroke-i-regressio, ad stroke-i-evolutio (Codes , Eighth Revisio, Iteratioal Classificatio of Diseases 3 ); we excluded trasiet ischemic attacks. was defied as a death occurrig withi 3 moths followig a stroke. Therefore, follow-up of the death certificates cotiued util March 31, Three types of stroke were defied: defiite stroke, diagosis made by a eurologist or a pathologist; probable stroke, diagosis made by a physicia ot a eurologist i a geeral or specific (geriatric) hospital; ad possible stroke,

2 726 Stroke Vol 20, No 6, Jue \ \ - _ - V V > FIGURE 1. Age-stadardized mortality rates from strokes i Israel, , by sex (solid lie, female; dashed lie, male) ad ethic group (, North Africa; O, Asia; U, Wester). Adapted from Epstei ad Zaaroor' with permissio. other diagosis of stroke recorded by a physicia ot a eurologist. To esure as complete coverage as possible, we used a umber of differet sources of data, icludig the departmets of eurology ad iteral medicie of the four geeral hospitals i the regio, the departmet of rehabilitatio medicie i oe of the above hospitals, ad the sigle geriatric rehabilitatio hospital i the regio. A specially traied registered urse visited each of these twice a week to review the charts of patiets i the hospital ad those discharged sice her previous visit ad to idetify ay patiets with oe of the relevat diagoses. Death certificates of persos residig i the subdistricts were reviewed by the urses weekly. These certificates are dispatched to the District Health Office i the regio from the area i which the perso died. Therefore, the records are complete, irrespective of where the idividual died. Iformatio obtaied from a umber of sources was combied o a sigle form for each idividual. We carried out a umber of additioal checks to ivestigate the possibility that ot all persos survivig a stroke were hospitalized. First, we cotacted the resposible professioals i old-age homes ad istitutios for the chroically ill i the regio every 2 moths ad requested iformatio as to the patiets who had suffered a stroke ad were ot hospitalized. Whe such a case was reported, a urse visited the istitutio to obtai as much data as possible o the idividual ad diagosis. Secod, a 15% radom sample of the geeral practitioers i the regio was selected every 2 moths ad the procedure described above was followed. However, after three such cotacts o ew cases udetected by the other methods were foud, ad the procedure was discotiued. Fially, a sample check was made of the emergecy room of oe of the uiversity hospitals i the regio. From all these efforts, it was cocluded that the data o diagosed cases of stroke i the study populatio were as complete as possible. ad mortality were calculated usig data from the 1983 Natioal Cesus as the deomiator. A 20% sample of the data was available o magetic tape. To compare icidece ad mortality amog the differet sex ad ethic groups, they were stadardized by the direct method usig the world populatio of 1970 as the stadard populatio. 4 Statistical sigificace was calculated usig the Z test for comparig two stadardized rates o two populatios, the x 2 test for comparig more tha two populatios, ad the t test to compare meas betwee two populatios. p<0.05 was cosidered to idicate statistical sigificace. Results We idetified 1,149 cases of stroke durig The ethic origi of the cases was Wester i 902 (78.5%), North Africa i 125 (10.9%), Asia i 121 (10.5%), ad Israeli i oe (0.1%; this sigle case was excluded from further aalyses). Amog the 590 me, 534 (90.5%) had suffered either a defiite or a probable stroke, while 485 (86.5%) of the 559 wome were so typed. Because oly oe autopsy was performed i the total series, the oly measure available to test the validity of our data is reflected by the proportio of defiite or probable strokes (1034, 90%). There were o sigificat differeces i the proportio of such diagoses by age, sex, or ethic origi. As part of the diagostic process, certai special diagostic ivestigatios were performed (electroecephalography i 820 [71.4%], computed tomography i 244 [21.2%], isotope scas i 217 [18.9%], cerebral agiography i 43 [3.7%], ad lumbar pucture i 256 [22.3%]). The data o the performace of these tests were lackig i 172 (15%) of the cases, most of whom had died outside hospital. There was o differece i the proportio of patiets udergoig these special ivestigatios by age, sex, or ethic origi. I both sexes, icidece rose with age (Table 1) ad was higher i me i all except the oldest (80+ years) age group. The total crude icidece rate for those older tha 44 years was 20% higher i me tha i wome. There were oly 15 cases i persos youger tha age 45 or whose age was ukow, ad these 15 were excluded from subsequet aalyses. Four hudred forty-eight persos died withi 3 moths after the acute evet, 276 (61.6%) of them i a hospital, 111 (24.8%) i a istitutio, 41 (9.1%) at home, ad 20 (4.5%) i a ukow place. There were o proportioal differeces i the place of

3 Epstei et al Stroke i Norther Israel 727 TABLE 1. Age- ad Sex-Specific of Stroke i Populatio of Jews i Norther Israel Age Me (=584) Wome (=550) (yr) Overall Data exclude 15 persos (six me ad ie wome) youger tha 45 years or i whom age was ukow. per 10,000 populatio. death by sex or ethic origi. However, those who died were, o the average, 5 years older tha those who survived (75.5 compared with 70.5 years; f=8.51,p<0.001). The case-fatality rate rose with age i both sexes (Table 2) ad was higher i wome tha i me at all ages. This differece was greatest i those youger tha 65 years ad became smaller with icreasig age. However, the age-stadardized icidece of stroke was higher i me tha i wome (60.68 compared with per 10,000; Z=3.00, p<0.003; Table 3). As i previous studies i Israel, the age-stadardized mortality from stroke was slightly, but ot sigificatly, higher i wome tha i me despite the substatially higher icidece of stroke i me. This fidig may be explaied by the fact that the age-stadardized case-fatality rate is almost twice as high i wome as i me (37.86% compared with 20.21%; Z=2.31, p<0.0104). Table 4 shows these fidigs i relatio to ethic origi. The age-stadardized icidece of stroke was higher i both me ad wome of North Africa ad Asia origi tha i those from Wester coutries. While the differeces were ot sigificat amog me, the rate amog wome of Wester origi was sigificatly lower tha that of North Africa wome (Z=2.37, p<0.02) ad of Asia-bor wome (Z=3.49, p<0.0002). The icidece was higher i me oly i the Wester group, but because of the relatively large umbers i this group, the overall icidece i me was sigificatly greater tha that i wome. There was little TABLE 2. Age- ad Sex-Spedfic 3-Moth Case-Fatality s From Stroke i Populatio of Jews i Norther Israel Age Me (=584) Wome (=550) (yr) < % % Data exclude 15 persos (six me ad ie wome) youger tha 45 years or i whom age was ukow. % of age group (data ot show). TABLE 3. Age-Stadardized ad (per 10,000 Populatio) ad Case-Fatality s (%) From Stroke by Sex i Populatio of Jews i Norther Israel Me Wome 60.68* Case-fatality rate 20.2 It *tp<0.003, , respectively, differet from wome by Z test. differece i mortality rates except i Asia-bor wome, whose rate was substatially higher tha that of Asia me ad sigificatly higher tha that of Wester wome (Z=2.26, p<0.025). Case-fatality rates were cosistetly higher i wome tha i me across ethic groups. This fidig was especially marked i the Wester ad Asia groups. Whereas the relatively few cases i each sex/ethic group resulted i these differeces ot reachig the level of sigificace, the cosistecy of these fidigs i all groups certaily cotributed to the highly sigificat differece i overall case-fatality rate betwee the sexes. A detailed cliical diagosis of the category of stroke was available i approximately 70% of both me ad wome. Withi these subgroups, 82.7% of the wome ad 81.8% of the me were diagosed as havig a cerebral ifarctio, whereas the proportios havig cerebral (subarachoid or itracerebral) hemorrhage were 7.4% ad 6.2%, respectively. i the two sexes was similar i each diagostic category, ad there were o differeces i the proportio of cases whe comparig the three ethic groups by sex. The proportio of those without a detailed diagosis was slightly lower i those of Asia origi i both sexes. Because of the small umbers, detailed comparisos of diagostic categories i each sex/ethic group was difficult, but o major differeces were readily apparet. I both me ad wome, approximately 85% of the kow diagoses amog those of North Africa ad Wester origi were cerebral ifarctio, while 5-9% were cerebral hemorrhage. I both me ad wome of Asia origi, the proportio havig cerebral ifarctio was slightly lower (75%) but the proportio havig cerebral hemorrhage was higher (10%). No differece was statistically sigificat. Discussio Adler 5 reported i 1969 o the epidemiologic ad cliical aspects of stroke i Israel durig the years Based oly o hospitalizatios, he foud that the icidece of stroke was higher i me ad its mortality lower i wome util the age of 60 years, after which it was higher i wome. I that study, the lack of data regardig either deaths or patiets survivig a stroke outside a hospital made it difficult to assess the validity of the relatios amog icidece, mortality, ad case-fatality rates.

4 728 Stroke Vol 20, No 6, Jue 1989 TABLE 4. Age-Stadardized ad (per 10,000 Poplatio) ad Case-Fatality s (%) From Stroke by Sex ad Ethic Origi i Poplatkm of Jews I Norther Israel Wester North Africa Asia Me Case-fatality Wome Case-fatality *t*p<0.02, , , respectively, differet from Wester wome * 29.2* t It is clear that with so few autopsies i Israel (ad oly oe i our series) questios regardig the validity of diagoses may arise. However, the proportios of cases hospitalized (88%), those with a stroke diagosed by a eurologist (90%), ad those udergoig the special diagostic ivestigatios was similar to or greater tha that reported from other commuity-based studies of stroke. 67 Thus, the validity of our diagoses should be similar ad should ot differ by sex or ethic group sice the proportios of our cases did ot vary with these characteristics. Further, whe comparig the proportio of those i whom a detailed diagosis of the category of stroke was made, there were o sigificat differeces by sex or ethic group. As expected, mortality from cerebral hemorrhage was substatially higher tha that from cerebral ifarctio but, oce agai, ot differet whe comparig ethic groups. The oly other icidece data from Israel are ot comparable with ours sice they do ot relate to the same populatio group. 8 The marked rise i icidece with age compares with fidigs from similar commuity studies i other coutries. I additio, it is of iterest to ote that the high icidece of stroke for me up to the oldest age group studied has bee reported i other studies, as has the relatively higher icidece i wome i the oldest age groups. The female prepoderace i case-atality rates has also bee reported i studies from the Netherlads 6 ad New Zealad. 7 However, oly the Dutch work reported a greater differece at youger ages. It should be stressed that comparisos are difficult because of the differet itervals used to calculate case-fatality rates. Our previous fidig 12 of higher stroke mortality i Israel from 1969 to 1982 amog wome ad amog those of North Africa origi of either sex was surprisig sice higher mortality from stroke amog wome has oly rarely bee reported. 910 I our preset study, the icrease seems to be related to both the slightly higher icidece i wome of Asia origi ad to the higher case-fatality rate i wome of all ethic groups. It should be clear that the higher rates i wome are ot explaied solely by their greater umbers i the older age groups sice the rates comparig ethic groups were all stadardized by age. These differeces could be attributed to various factors that modify ad ifluece the pathogeesis of the stroke ad its cliical course, such as the distributio of risk factors for the disease (e.g., hypertesio or smokig), a differet pathophysiology of the disease i differet ethic groups, differeces i the idetificatio ad possible treatmet of persos at risk, a delay i seekig medical care after the start of a acute episode, a delay or error i diagosis that differs amog ethic groups, ad varyig resposes to supportive therapy. It must be stated that there is relatively little data that ca adequately aswer these questios. I 1961, Dreyfuss et al 11 observed that immigrats from Morocco i North Africa had higher blood pressures tha expected whe they arrived i Israel. While later studies have ot revealed cosistet differeces i this coectio, Moda 12 has reported a higher prevalece of hypertesio i this ethic group from a study of a represetative sample of male ad female Israeli Jews aged years. The possibility arises that differeces i the distributio of hypertesio, a major risk factor for stroke, could partially explai our fidigs. A atioal program related to the early diagosis of hypertesio ad its subsequet maagemet is coducted by Kupat Holim, the Health Isurace Istitute of the Geeral Federatio of Labor, with which >85% of the populatio are isured. There are, however, o data available o differetial case fidig or respose to treatmet i the groups idetified i that program. A recet report 13 idicated that wome with acute myocardial ifarctio teded to begi treatmet later tha me. A questio arises as to whether this is true with stroke as well ad whether it provides a possible explaatio for the sex ad ethic differeces foud. There is little doubt that illess behavior varies i the differet groups of the heterogeeous ethic society of Israel. Its specific

5 relevace to the atural history of stroke eeds to be ivestigated. Differeces i the pathophysiology of stroke may certaily occur. Some years ago, differeces i the developmet of atherosclerosis i the circle of Willis of me ad wome were reported. H Boita et al 7 have idicated that cerebral hemorrhage is more frequet i females ad produces a higher mortality. We foud o differeces i the proportio of cases with cerebral hemorrhage amog the 70% i whom the category of stroke was determied. Differeces i icidece, mortality, ad casefatality rates from ay disease have importat implicatios for the plaig of medical care for differet populatio groups. Our fidigs uderlie the eed to ivestigate further the processes uderlyig these differeces ad to adapt available services to the problems i relatio to both the prevetio ad the maagemet of all stages of the disease process. Refereces 1. Epstei L, Zaaroor M: from ischemic heart disease ad cerebrovascular disease i Israel, Stroke 1982;13:57O Epstei L, Strulov A: Possible ifluece of chages i risk factors o cardiovascular morbidity ad mortality i Israel: Need for a iformatio system. Isr J Med Sci 1986;22: World Health Orgaizatio: Maual of the Iteratioal Statistical Classificatio of Diseases, Ijuries ad Causes of Death. Based o the recommedatios of the 8th Revisio Coferece. Geeva, World Health Orgaizatio, 1967 Epstei et al Stroke i Norther Israel Doll R, Muir C, Waterhouse J: Cacer i Five Cotiets, vol 2. Berli, Spriger-Verlag, Adler E: Stroke i Israel Jerusalem, Polypress Ltd, Herma B, Leyte ACM, va Lmjk JH, Freke CWGM, Op de Coul AAW, Schulte BPM: Epidemiology of stroke i TUburg, The Netherlads. The populatio-based stroke icidece register 2., iitial cliical picture ad medical care, ad three week case fatality. Stroke 1982; 13: Boita R, Beaglehole R, North JDK: Evet, icidece ad case fatality rates of cerebrovascular disease i Aucklad, New Zealad. Am J Epidemiol 1984,120: Maelis G, Shasha S, Maelis J, Cohe D: Cerebro-vascular accidets amog the Druze of the Wester Galilee. Frotiers of Iteral Medicie, the 12th Iteratioal Cogress of Iteral Medicie, Tel Aviv, Basel, Karger, 1975, pp Habea S, Capildeo R, Rose FC: The chagig mortality of cerebrovascular disease. Q J Med 1978;47: Haberma S, Capildeo R, Rose FC: Sex differeces i the icidece of ccrebrovascular disease. J Epidemiol Commuity Health 1981;35:45-5O 11. Dreyfuss F, Hamosh P, Adam Y, Kaller B: Coroary heart disease ad hypertesio amog Jews immigrated to Israel from the Atlas Moutai regios of North Africa. Am Heart J1961;62: Moda M: Natiowide study of hypertesio i Israel, i Thurm RH (ed): Essetial Hypertesio. Miami, Symposia Specialists, 1979, p Tu GZ, Stoe PH, Muller JE, Parker C, Rude RE, Raabe DE, Jaffe AS, Hartwell TD, Robertso TL, Brauwald E, ad the MILIS Study Group: Implicatios for acute itervetio related to time of hospital arrival i acute myocardial ifarctio. Am J Cardiol 1986^7: Baker AB, Katsuki S: Strokes: A study of a Caucasia ad a Orietal populatio. Mod Med 1969;17: KEY WORDS Israel cerebrovascular disorders mortality