Stroke is the most common cause of death in China. 1,2 The

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1 Proportio of Differet Subtypes of Stroke i Chia Li-Feg Zhag, MD; Ju Yag, MD; Zhe Hog, MD; Guag-Gu Yua, MD; Bei-Fa Zhou, MD; Lia-Cheg Zhao, MD; Yi-Nig Huag, MD; Jie Che, MD; Yag-Feg Wu, MD, PhD; for the Collaborative Group of Chia Multiceter Study of Cardiovascular Epidemiology Backgroud ad Purpose The goal of this article is to clarify the proportio of stroke subtypes i Chia, where stoke is the most commo cause of death. Methods A total of first-ever strokes i subjects 25 years of age were idetified i 1991 to 2000 from 17 Chiese populatios through a commuity-based cardiovascular disease surveillace program i the Chia Multiceter Collaborative Study of Cardiovascular Epidemiology. World Health Orgaizatio diagosis criteria were used for classificatio of stroke subtypes. Results CT sca rate of stroke cases reached a satisfactorily high level oly after 1996 i the study populatios. I 8268 first-ever stroke evets from 10 populatios with CT sca rate 75 i 1996 to 2000, 1.8 were subarachoid hemorrhage, 27.5 were itracerebral hemorrhage, 62.4 were cerebral ifarctio, ad 8.3 were udetermied stroke. The proportio of itracerebral hemorrhage varied from 17.1 to 39.4 ad that for cerebral ifarctio varied from 45.5 to 75.9 from populatio to populatio. The ratio of ischemic to hemorrhagic stroke raged from 1.1 to 3.9 ad averaged 2.0). The 28-day fatality rate was 33.3 for subarachoid hemorrhage, 49.4 for itracerebral hemorrhage, 16.9 for cerebral ifarctio, ad 64.6 for udetermied stroke. Coclusios I our study, ischemic stroke was more frequet ad its proportio was higher tha hemorrhagic stroke i Chiese populatios. Although hemorrhagic stroke was more frequet i Chiese tha i Wester populatios, the variatio i the proportio of stroke subtypes amog Chiese populatios could be as large as or larger tha that betwee Chiese ad Wester populatios. (Stroke. 2003;34: ) Key Words: Chia epidemiology stroke Stroke is the most commo cause of death i Chia. 1,2 The risk factor profiles ad prevetio strategies are differet for ischemic ad hemorrhagic stroke, 3 so it is importat to clarify the proportio of stroke subtypes. Most previous studies suggested that at least 30 of strokes i Chia were hemorrhagic strokes 4,5 ; some studies eve reported that 50 of strokes were hemorrhagic, 6 which was sigificatly differet from the fidigs i whites However, most of these previous studies either limited the study populatio to a cofied area or based the diagosis criteria maily o cliical presetatios. I recet years, CT sca rate of stroke patiets has icreased rapidly, which makes it possible to examie the stroke subtypes more accurately i Chiese populatios. I this article, we use data from the Chia Multiceter Collaborative Study of Cardiovascular Epidemiology, a log-term, ogoig, large-scale project supported by the Chiese cetral govermet, to clarify the relative proportios of stroke subtypes i Chiese populatios ad stroke fatality by differet subtypes to provide a scietific base for makig a appropriate stroke prevetio strategy i the most populous coutry i the world. Subjects ad Methods Chia Multiceter Collaborative Study of Cardiovascular Epidemiology The Chia Multiceter Collaborative Study of Cardiovascular Epidemiology was iitiated i 1982 by the Departmet of Epidemiology, Cardiovascular Istitute ad Fu Wai Hospital, Chiese Academy of Medical Scieces, supported by the Chia Miistry of Sciece ad Techology through a series of atioal 5-year plas. 17 It was origially desiged as a cross-sectioal multiceter compariso of cardiovascular diseases risk factors ad was later developed ito a comprehesive epidemiological study that icluded 3 major compoets: populatio disease surveillace of cardiovascular disease morbidity ad mortality, populatio samplig surveys of cardiovascular disease risk factors, ad cohort follow-up of cardiovascular outcomes to moitor the treds of cardiovascular disease ad risk factors ad to pipoit the major determiats of cardiovascular Received Jauary 13, 2003; fial revisio received April 11, 2003; accepted May 20, From the Departmet of Epidemiology, Cardiovascular Istitute ad Fu Wai Hospital, Chiese Academy of Medical Scieces ad Pekig Uio Medical College (L.-F.Z., J.Y., L.-C.Z., B.-F.Z., Y.-F.W); Departmet of Neurology, Huasha Hospital, Medical College of Fuda Uiversity, Shaghai (Z.H.); Departmet of Neurology, West Chia Hospital, Sichua Uiversity, Sichua (G.-G.Y.); Departmet of Neurology, Pekig Uio Medical College Hospital, Chiese Academy of Medical Sciece, Beijig (Y.-N.H.); ad Natioal Office for Cardiovascular Disease Cotrol ad Research (J.C.), People s Republic of Chia. Reprit requests to Dr Yag-Feg Wu, MD, PhD, Departmet of Epidemiology, Cardiovascular Istitute ad Fu Wai Hospital, Chiese Academy of Medical Scieces ad Pekig Uio Medical College, Bei Li Shi Rd 167, Beijig, , People s Republic of Chia. tsq@public.east.et.c 2003 America Heart Associatio, Ic. Stroke is available at DOI: /01.STR C 2091

2 2092 Stroke September 2003 Geographic locatio of study populatios i the Chia Multiceter Collaborative Study of Cardiovascular Epidemiology. disease i the mailad of Chia. All compoets ivolved multiceter participatio. Study Populatios As part of the Chia Multiceter Collaborative Study of Cardiovascular Epidemiology, the populatio disease surveillace program (of cardiovascular disease morbidity ad mortality) from 1991 to 2000 used the World Health Orgaizatio Moitorig of Treds ad Determiats i Cardiovascular Disease (WHO MONICA) diagosis criteria 18,19 for cardiovascular disease evets. It bega with 14 populatios i 1991, ad 2 of them stopped i However, the study expaded to 15 populatios i 1996 by addig 3 ew populatios. Thus, we have data for aalysis of 14 populatios from 1991 to 1995, of 15 populatios from 1996 to 2000, ad of 12 populatios from 1991 to These populatios were ot selected radomly from the whole atio but were selected o the basis of the mai characteristics of the populatio i terms of socioecoomic TABLE 1. Characteristics of First-Ever Stroke Evets i Subjects >25 Years of Age First-Ever Stroke Evets, status, geographical locatios, ad dietary patters. The geographical locatios of these populatios are show i the Figure. The study duratio ad populatio characteristics are listed i Table 1. Of the 17 populatios overall, 9 were from rural residetial areas ad 8 were from urba residetial areas. Amog the rural populatios, 2 were from islets at the east coast of Chia, 1 i the orth part ad 1 i the south part. Amog the urba populatios, 3 were from livig areas maily for families of workers i the large idustrial maufacturers, the Capital Iro-Steel Complex (CISC) i Beijig, the Guagzhou Shipyard i Guagzhou, ad the CISC mie i Qia a. I each populatio, we chose a geographically ad admiistratively welldefied commuity with residets i all ages as the study populatio, except for Chagdao, accordig to its represetativeess of the local populatio i terms of ecoomy developmet, stadard of livig, educatio level, ad occupatio. All populatios were covered by the govermetal household register system, which documeted the eterig of the subjects as ewbors or by movig ito the area ad the leavig of the subjects whe they moved from the area or died. Thus, iformatio o the exact size, age, ad sex structure of the study populatios was obtaied aually from the local admiistratio offices. The populatio size i mid-2000 was give by the study populatios i Table 1. Defiitio of Stroke ad Classificatio of Stroke Subtypes Stroke was defied accordig to the WHO MONICA criteria 18 :a sudde oset of focal (or global) disturbace of cerebral fuctio lastig 24 hours (uless iterrupted by surgery or death) with o apparet ovascular cause. The defiitio icluded patiets presetig with cliical sigs ad symptoms suggestive of complete stroke, icludig cerebral ifarctio (CI), itracerebral hemorrhage (ICH), ad subarachoid hemorrhage (SAH). Trasiet ischemic attacks ad silet brai ifarctios (cases without cliical symptoms or sigs) were ot icluded; either were evets associated with trauma, blood disease, or maligacy. All suspected stroke evets were first classified ito defiite stroke, defiite stroke associated with defiite myocardial ifarctio, ot stroke, or isufficiet s by Age, Populatio Study Duratio Socioecoomic Status Populatio i 2000, Xicheg, Beijig Developed urba Shaghai Developed urba Shijigsha, Beijig Developed rural CISC, Beijig Developed urba Yuxia Rural Deyag Urba Shipyard, Guagzhou Developed urba Payu, Guagzhou Developed rural Jita Rural Zhousha Coastal islets Hazhog Rural Wumig Rural Male s Hospitalized, 28-Day Qia-a Large idustry * residetial area Harbi Urba * Mudajiag Urba Zhegdig Rural Chagdao Coastal islets Total *Populatio i 1995.

3 Zhag et al Proportio of Differet Subtypes of Stroke i Chia 2093 data by the cetrally traied local physicia resposible for evet diagosis o the basis of all available iformatio, as doe i the MONICA project. Classificatio was doe etirely o cliical presetatios. A stroke episode that occurred 28 days after the previous oe was cosidered a recurret stroke. The, all cases idetified as defiite stroke ad defiite stroke associated with defiite myocardial ifarctio were further classified ito SAH, ICH, CI, ad udetermied stroke (UND) ad coded with the ith revisio of the Iteratioal Classificatio of Diseases (ICD-9). The classificatio of SAH, ICH, ad CI was doe o the basis of cliical presetatio, ad cofirmatio by CT was required, with referece to the MONICA criteria. UND icluded all cases that either had ot had CT sca or could ot be classified by CT sca fidigs. Although the stroke evets icluded first-ever ad recurret stroke, oly first-ever strokes were used for aalysis. Ascertaimet A 3-level case reportig ad ascertaimet system was established to fuctio i the disease surveillace program i the Chia Multiceter Collaborative Study of Cardiovascular Epidemiology. All suspected cases were first reported to the local ceters by the primary healthcare workers i rural populatios, household admiistrative workers, ad doctors i primary hospitals or health statios i urba populatios. The local ceter would sed a traied staff member to the locatio of the suspected patiet, after receivig iformatio from the first-level moitors, to collect all iformatio related to the diagosis of stroke to complete the registratio. If a patiet was hospitalized, discharge iformatio was obtaied. If a patiet died, iformatio o the death certificate was required. If a patiet was ot admitted to the hospital, disease iformatio was collected from either the relatives (fatal) or the patiet (ofatal). The registratio form was the brought back to the diagosis committee, which was composed of 2 or 3 qualified physicias at the local ceter. The local diagosis committee the made a prelimiary diagosis o the basis of all available iformatio ad coded each evet accordig to ICD-9. The, all registratio forms were set to the coordiatig ceter, where all the iformatio was rechecked ad the fial diagosis was give by the cetral diagosis committee, which cosisted of eurologists, cardiologists, ad epidemiologists. Data Quality ad Statistical Aalysis The registratio form was cetrally desiged with referece to that used i the MONICA project ad distributed to all local ceters. The resposible physicias at the local ceters were traied ad certified cetrally by the Coordiatig Ceter ad were resposible for traiig of the first-level moitors uder the local ceter accordig to a uiform protocol. The evet-missig rate was estimated aually by local ceters usig data obtaied from a door-to-door survey i a radom sample of 5 to 10 of the study populatios. The estimated evet-missig rate was geerally 5. Double etry of data was used at local ceters, ad data submitted to the Coordiatig Ceter were checked for completeess, logical cosistecy, ad duplicatio. I this article, we icluded i our aalysis oly first-ever, defiite stroke evets i subjects 25 years of age. The proportio of stroke subtypes was defied by dividig the frequecy of the stroke subtype by the total frequecy of stroke. s hospitalized icluded those ever treated i a hospital but ot those oly treated i a rural village cliic or i a urba health statio. The 28-day case fatality rate was defied as the frequecy of cases who died withi 28 days after the oset of stroke divided by the total frequecy of stroke. The ratio of ischemic to hemorrhagic stroke (IS/HS) was calculated as the ratio of the frequecy of ischemic stroke to the frequecy of hemorrhagic stroke. The differeces i proportio of stroke subtypes ad i 28-day fatality were tested with the 2 test, ad the treds of the rates with age were tested with the 2 test for a liear tred of proportios. Test results yieldig 2-tail values of P 0.05 were cosidered statistically sigificat. TABLE 2. Proportio of Stroke Subtypes i Differet Years i s >25 Years of Age Amog 12 Populatios From 1991 to 2000 Moitor Year Total SAH, Results Characteristics of First-Ever Stroke s Durig 1991 through 2000, a total of first-ever stroke evets i persos 25 years of age were idetified amog all study populatios. Of these, 59.0 were me, 4.0 were 44 years of age, 41.2 were 45 to 64 years of age, ad 54.8 were 65 years of age. The mea age was 64.9 years for me ad 66.6 years for wome. The umber of cases hospitalized was geerally high, 83.3 o average (higher for developed urba populatios ad lower for rural populatios). The 28-day case fatality was geerally lower i developed urba populatios ad higher i rural populatios ad was 35 o average. The characteristics of the cases are show i detail i Table 1. ICH, Chages i Proportio of Stroke Subtypes ad CT Sca Rate i Chia From 1991 to 2000 Table 2 shows the chages i frequecy ad proportio of stroke subtypes, as well as the CT sca rate over 10 years (from 1991 to 2000), amog 12 populatios that had complete data durig the period. Data clearly showed that the CT sca rate i Chia icreased markedly durig the 10 years, from 50 to 90. As a result, the proportio of UND decreased remarkably from 50 to 10; at the same time, the proportios of both hemorrhagic stroke ad ischemic stroke icreased sigificatly. I 2000, SAH, ICH, CI, ad UND accouted for 1.1, 28.5, 61.9, ad 8.6, respectively, of the overall populatio. Proportio of Stroke Subtypes i Differet Populatios i Chia To miimize the ifluece of CT sca rate o study results, Table 3 limited the aalysis to data from 1996 ad 2000 ad to the populatios with the CT sca rate 75 to aalyze the proportio of differet stroke subtypes. As a result, o average, 1.8 were SAH, 27.5 were ICH, 62.4 were CI, ad 8.3 were UND. The proportios of ICH ad CI varied from populatio to populatio, but SAH did ot vary much. IS/HS raged from 1.1 to 3.9 ad averaged 2.0. Although the variatios i the proportios could ot be explaied fully by CI, UND, Total CT,

4 2094 Stroke September 2003 TABLE 3. Proportio of Stroke Subtypes Amog 10 Populatios With CT Sca Rate >75 From 1996 to 2000 Populatio Total SAH, ICH, CI, UND, IS/HS CT, Mudajiag Xicheg, Beijig Shaghai Shipyard, Guagzhou Shijigsha, Beijig Payu, Guagzhou CISC, Beijig Deyag Yuxia Zhegdig Total the variace i CT sca rate, ischemic stroke was demostrated to be the domiat subtype. Proportio of Stroke Subtypes i Relatio to Age ad Sex To further uderstad the factors besides CT sca rate that may affect the proportios of stroke subtypes, the proportio of stroke subtypes by age ad sex i the 10 populatios with CT sca rate 75 durig the period of 1996 through 2000 is show i Table 4. The proportio of stroke subtypes was similar i me ad wome, but there were more hemorrhagic strokes i the youger group tha i the older group i both sexes. Withi 28 Days i Relatio to Stroke Subtypes, Age, ad Sex Table 5 gives the umber ad rate of death at 28 days for first-ever stroke cases by subtype of stroke, age of oset, ad sex. O average, 33.3 of the first-ever SAH stroke cases TABLE 4. Frequecy ad Proportio of Stroke Subtypes by Sex ad Age i Populatios With CT Sca Rate >75 From 1996 to 2000 Age Group Total SAH, ICH, CI, UND, Me P for tred Wome P for tred All me All wome Total died withi 28 days, 49.4 of ICH cases, 16.9 of CI cases, ad 64.6 of UND cases. The 28-day fatality rate icreased sigificatly with age for both CI ad ICH i both sexes, icreased sigificatly for SAH i wome, but did ot vary much with age for UND. Discussio Geeralizability of Our Fidigs Populatio-based epidemiological studies o stroke are scarce i Chia; multiceter studies are eve fewer. I fact, there were oly 2 populatio-based multiceter studies of stroke that used WHO MONICA diagosis criteria. 20 Because CT sca became popular oly very recetly (as show by our data), it made our study uique, with accurate data from multiple populatios to clarify the proportio of stroke subtypes i Chiese populatios. Furthermore, a uiform protocol ad registratio form ad cetral traiig were used i all study populatios from start to ed, which allowed the comparability i differet populatios i the preset study. Although the study populatios were ot radomly selected from the whole atio, they were selected after careful cosideratio of mai residetial districts, major stratums of socioecoomic developmet, ad dietary lifestyles. Some idustrial residetial areas were selected to take advatage of their admiistratio systems to icrease the feasibility of coductig the study, but the whole populatio was put ito the case registratio system of the study. Thus, fidigs from our study should well reflect the curret actual pictures i Chia with differet populatios at differet stages of social developmet. What is the Domiat Subtype of Stroke i Chia? Our data from 1996 to 2000 i populatios with CT sca rate 75 demostrated that the proportios of CI raged from 49.3 to 75.9, ad IS/HS ratios were all 1. O average, oe third were hemorrhagic ad two thirds were ischemic. Thus, we cocluded that ischemic stroke was the domiat subtype i terms of quatity of icidet cases i Chiese populatios, as log as high-quality data were available. This fidig was similar to those reported elsewhere i the world 7 16 but cotradicted fidigs from some studies i Chiese populatios 6 i which hemorrhagic stroke was reported to accout for as much as The reasos for the differece betwee our study ad the previous studies iclude differeces i methodology, CT sca rate, age limitatios of study populatio, etc. O the other had, our data idicated that the 28-day fatality was 20 for ischemic stroke but as high as 60 for hemorrhagic (ICH ad SAH) stroke. Thus, i terms of risk of mortality (by multiplyig proportio of stroke subtype with the 28-day fatality), the 2 types of stroke were almost idetical i Chiese populatios. This implies that the prevetio ad treatmet of hemorrhagic stroke are as importat as that of ischemic stroke from the public health poit of view. Stroke Subtypes i Chiese Populatios Compared With Wester Populatios Racial-ethic differeces i the subtypes of stroke have previously bee reported betwee Asias ad whites. 7 16

5 Zhag et al Proportio of Differet Subtypes of Stroke i Chia 2095 TABLE 5. ad Sex The 28-Day Rates of Differet Stroke Subtypes by Age SAH ICH CI UND Death, Death, Death, Death Age Group, y Me P for tred Wome P for tred All me All wome Total Previous studies i Chia, Hog Kog, Taiwa, ad Japa geerally foud that 23 to 52.2 of strokes were hemorrhagic, 3 6,21 25 i cotrast to oly 9 to 18 i whites I the preset study, 29.6 of stroke cases overall i 2000 were hemorrhagic i Chiese populatios, which supported the above idea that a ethic differece existed betwee Easter ad Wester populatios. Further aalysis showed that the proportio of hemorrhagic stroke amog all strokes varied from 19.4 to 42.2 i the 10 populatios, although all the study populatios came from the same race, Ha people. I compariso, a populatio-based study i Australia 7 foud that 18.8 were hemorrhagic stroke. This suggested that racialethic differeces i stroke subtypes idetified previously may actually uderlie differeces i lifestyles, diet, ad other evirometal factors rather tha geetics. Factors Associated With the Variace of Subtypes of Stroke Our study is the first i the world to fid a great variace i the proportio of stroke subtypes amog differet populatios with the same ethic backgroud ad withi the same coutry. Thus, the differece iduced by geetic diversity, if it exists, may ot play a major role i the large variace amog Chiese populatios ad may play oly a small role i the differece betwee Easter ad Wester populatios. To explore the factors that may explai the above variace i stroke subtypes i Chiese populatios, we first aalyzed the associatio of the IS/HS ratio to CT sca rate amog these populatios. The results showed that the correlatio coefficiet was 0.26 (P 0.46). Ad i populatios with the CT sca rates 90, the ratio still varied sigificatly. So, the variace i CT sca rate could ot explai the variace i IS/HS. Aother explaatio may ivolve the icompleteess of case ascertaimet. I rural populatios, medical resources were iadequate, ad the rate of hospitalizatio was cosiderably lower (as show by our data), so less severe or silet cases presetig miimum symptoms or sigs or cases who died before beig admitted to a hospital ad without autopsy might be missed; this might lead to a higher proportio of hemorrhagic stroke i rural populatios. However, this could ot be the mai reaso because, i our study, a populatiobased case-reportig system istead of a hospital-based registratio was used, ad the evet-missig rates were mostly 5, withi a acceptable limit. We compared the hospitalized cases ad uhospitalized cases i terms of age ad sex distributio ad foud o differeces. I additio, there was still sigificat variatio just i the developed urba populatios. Further aalysis idicated that there were more hemorrhagic strokes i the youger group tha i the older group. The age-stadardized proportios of stroke subtypes, however, still varied to about the same extet as the ustadardized proportios. Thus, the age differece amog these populatios caot be the mai reaso for such a variatio. The most probable reasos were the differeces i stroke risk factor profiles betwee the populatios studied. Our previous study 26 idicated that high serum cholesterol ad body mass idex would icrease the risk of ischemic stroke but ot hemorrhagic stroke, which was i accordace with fidigs from other studies. 3 Studies i Chia also showed that serum cholesterol was higher i urba tha i rural populatios ad higher i orther tha i souther populatios. 17,27 The preset study also showed a higher proportio of ischemic stroke ad a lower proportio of hemorrhagic stroke i urba ad orther populatios i Chia. Compared with Wester populatios, Easter populatios like Chiese ad Japaese have a lower level of serum cholesterol ad body mass idex, mostly because of their very differet lifestyle ad dietary patters, ad have relatively more hemorrhagic strokes. This hypothesis ca explai ot oly the variace amog Chiese populatios but also the differece betwee Chiese ad Wester populatios.

6 2096 Stroke September 2003 I summary, our study foud that ischemic stroke was more frequet ad the proportio was higher tha hemorrhagic stroke i Chiese populatios. Although hemorrhagic stroke was ot the predomiat subtype of stroke i Chiese, it was more frequet i Chiese tha i Wester populatios. The differece i stroke subtypes betwee Chiese ad Wester populatio ad betwee Chiese populatios may be due maily to differet cardiovascular risk factor profiles iduced by lifestyles, dietary patters, ad other evirometal factors. Ackowledgmets This work was supported by the Natioal Nith Five-Year Pla Sciece ad Techology Key Projects i People s Republic of Chia (grat ). Local pricipal ivestigators of the Collaborative Research Group of Chia Multiceter Study of Cardiovascular Epidemiology were as follows: Yi-He Li, Xiao-Qig Liu, Guagdog Provicial Cardiovascular Istitute, Guagdog Provice; Xue-Hai Yu, CISC Geeral Hospital, Beijig; Xiu-Zhe Tia, Shijigsha Istitute of Chroic Diseases Prevetio, Beijig; Li- Mi Liu, Shu-Yig Xia, Zhejiag Medical Uiversity, Zhejiag Provice; Lia-Sheg Rua, Putuo Health Bureau, Zhousha, Zhejiag Provice; Hai-Ya Wag, Wei-Chog Qia, Jiagsu Provicial People s Hospital, Jiagsu Provice; Li-Guag Zhu, Guagxi Medical Uiversity, Guagxi Provice; Dog-Shuag Guo, Yuxia People s Hospital, Shaxi Provice; Ju Yag, Hazhog Cardiovascular Istitute, Shaaxi Provice; Qi-Yu Yi, CISC Qia-a Mier s Hospital, Hebei Provice; Yig-Ru Gou, Huaxi Hospital, Sichua Provice; Zhe Hog, Hua-sha Hospital, Shaghai, Jia-Bo Lu, Hebei Cardiovascular Istitue, Hebei Provice; Chag- Ju Chu, Ji-Da Gu, Chagdao People s Hospital, Shadog Provice; Hog Yu, Yi Yag, Mudajiag People s Hospital, Heilogjiag Provice; Yu-Chu Yag, Harbi Medical Uiversity, Heilogjiag Provice; Zhao-Su Wu, Gui-Xia Wu, Beijig Istitute of Heart, Lug, ad Blood Vessel Diseases, Beijig. 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