Incidence and Trends of Stroke and Its Subtypes in China

    the Department of Neuroepidemiology (B.J., W.-Z.W., S.-P.W., X.-L.D., Q.-J.B.), Beijing Neurosurgical Institute, China
    Department of Neuroepidemiology (Z.H.), Institute of Neurology, Huashan Hospital, Medical College of Fudan University, Shanghai, China
    Department of Neuroepidemiology (Q.-D.Y.), Institute of Neurology, Xiangya Hospital, Medical College of Zhongnan University, Changsha, People’s Republic of China
    Epidemiology Branch, National Institute of Environmental Health Sciences (H.C.), Research Triangle Park, NC.

    Abstract

    Background and Purpose— To examine the incidence and trends of stroke and its major subtypes during the 1990s in 3 cities in China.

    Methods— Stroke cases registered between 1991 to 2000 were initially identified through the stroke surveillance networks established in Beijing, Shanghai, and Changsha, and then confirmed by neurologists.

    Results— The age-standardized incidence rates per 100 000 person years of overall first-ever stroke were 135.0 (95% CI, 126.5 to 144.6) in Beijing, 76.1 (70.6 to 82.6) in Shanghai, and 150.0 (141.3 to 160.0) in Changsha during the 1990s. Incidence of ischemic stroke (IS) was highest in Beijing, followed by Changsha and Shanghai; for intracerebral hemorrhage (ICH), the highest rate was found in Changsha, followed by Beijing and Shanghai. The same order as ICH was also observed for subarachnoid hemorrhage. The age-adjusted incidence of overall stroke and ICH for individuals 55 years of age in our populations was generally higher than that from Western populations. During the 1990s, ICH incidence decreased significantly at a rate of 12.0% per year in Beijing, 4.4% in Shanghai, and 7.7% in Changsha; in contrast, except for Changsha, IS incidence increased in Beijing (5.0% per year) and Shanghai (7.7%).

    Conclusions— There is a geographic variation in the incidence of stroke and its subtypes among these 3 cities, but the incidence of overall and hemorrhagic stroke in China is generally higher than that in the Western countries. Interestingly, the decrease in ICH and increase in IS during the past decade may reflect some underlying changes of risk factors in Chinese populations.

    Key Words: epidemiology  stroke  incidence

    Introduction

    In China, the incidence of stroke is higher than that of coronary heart disease,1 and the proportion of hemorrhagic stroke is also high.2,3 These epidemiological features are very different from those of Western countries1–5 and may imply different risk factor profiles.

    Stroke is not a homogeneous condition but rather a mix of clinically distinct subtypes that have different etiological and epidemiological characteristics. Although ischemic stroke (IS) and hemorrhagic stroke share some common risk factors such as age and hypertension, the population-attributable risks from these individual risk factors vary by stroke subtypes, and thus the prevention strategies are also different. Therefore, from a public health perspective, it is important to understand the incidence and secular trends of stroke subtypes in rapidly developing areas such as China.

    In the 1990s, we conducted a large-scale community-based stroke prevention trial in Beijing, Shanghai, and Changsha, 3 cities with high stroke incidence.6,7 Intervention included community-based health education and management of high-risk population in the intervention communities but no special intervention in the control communities. For this trial, we established community-based stroke surveillance networks in all research communities. Here, by taking advantage of the stroke surveillance data in the control communities, we examined the incidence and trends of stroke and its major subtypes in these 3 cities.

    Subjects and Methods

    Study Populations

    Beijing, Shanghai, and Changsha are 3 cities located respectively in the northern, eastern, and central southern parts of China. The design and method of the intervention trial have been published previously.7 Briefly, 2 communities, each with 50 000 residents of similar age and gender distributions, were selected in each city as either the intervention or control community. The current investigation was limited to the control populations. Annual demographic information on age and gender distributions of each community was obtained from local police stations during 1991 to 2000. Temporary residents and individuals who registered in the local police stations but did not actually reside in the communities were excluded.

    Stroke Report Network

    At the beginning of the intervention trial, community-based stroke surveillance networks were established in all research communities to identify incident stroke cases.7 Three centers, the Beijing Neurosurgical Institute, the Institute of Neurology at Huashan Hospital in Shanghai, and the Institute of Neurology at Xiangya Hospital in Changsha, collaborated in the study design and data collection. Doctors of the preventive medicine departments in local community hospitals, which provide basic and comprehensive medical and public health services to local residents in China, were recruited in this project as our grassroots network. They established close ties with directors of local residents committees (RCs) and building gate volunteers who were trained to identify and report stroke cases.

    Case Ascertainment and Quality Control

    During the study period, possible stroke cases were initially reported to the 3 collaborating centers through the public health workers, who got the information from directors of RCs or building gate volunteers when doing their daily routines. The centers then sent a neurologist or neurosurgeon to visit the patient at home or hospital as soon as possible. Detailed clinical information on each case, including clinical signs and symptoms, previous medical history, medication, and computerized tomography (CT)/MRI results, was obtained during the visit. Cases that did not go to the hospital or died at home (5.2% of first-ever stroke) were also identified during medical workers’ routines and supplemented by our annual door-to-door inquiries to the RCs directors and building gate volunteers for each building. Such surveys were conducted annually from January to March by the research group, and the research team would pay a home visit immediately if a case was identified during the survey. Fatal stroke patients who died at home were obtained from eyewitnesses (patients’ relatives) and monthly review of death certificates. In China, all deaths are legally required to be reported by patients’ relatives to the local medical workers for cremation and household cancellation.

    To ensure the quality of information collection, all staff members, including the public health workers, received annual training on how to survey and register incident stroke patients according to our standard operational manual. Further, investigators from all 3 centers met annually to review research progress and to resolve problems encountered during study.

    Stroke Diagnosis and Classification

    The diagnosis and classification of stroke were performed according to a slightly revised version of the one used in the Atherosclerosis Risk in Communities (ARIC) Study.8 Briefly, the minimum criteria for a definite or probable stroke diagnosis included evidence of sudden or rapid onset of neurological symptoms lasting for >24 hours or leading to death in the absence of evidence for a nonstroke cause. Exclusions included major brain trauma, neoplasm, coma attributable to metabolic disorders or disorders of fluid or electrolyte balance, vasculitis involving the brain, peripheral neuropathy, hematologic abnormalities, or central nervous system infections. Transient ischemic attacks and silent brain infarctions (cases without clinical symptoms and signs) were not included.

    Stroke subtypes were defined according to published criteria8 and then grouped into 3 major types: IS (including thrombotic brain infarction, cardioembolic stroke, and lacunar infarcts), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage. Cases that fell in 2 different diagnostic categories or did not go to the hospital or died at home were assigned as undetermined stroke.

    Statistical Analysis

    The incidence of first-ever stroke and its major subtypes was calculated by dividing the number of incident cases by person years of follow-up. The incidence of overall age groups was directly standardized to the 5-year age distribution of the Segi’s world population. The 95% CIs for all incidence rates were also calculated.9 The incidence of stroke for participants 55 years of age in these 3 urban populations was compared with that from other populations and standardized to the 10-year age distribution of the Segi’s world population.

    The average annual change in stroke incidence was calculated by using a regression model: log(Rt)=+·t. Annual percentage change equals 100·(exp–1), where  is the maximum likelihood estimate of the slope parameter and exp estimates the relative risk associated with 2 consecutive years. Because (exp–1) approximates  for small changes, 100· percent of the incidence rate at time t is given to denote the instantaneous change rate per year at time point t. Age-standardized incidence was used in this analysis.1

    Results

    Patient Characteristics

    During 1 505 176 person years of follow-up, we identified a total of 3015 patients with a first-ever stroke in the 3 urban communities, including 1643 (54.5%) cases of cerebral infarction, 1157 (38.4%) ICHs, 34 (1.1%) subarachnoid hemorrhages, and 181 (6.0%) unclassifiable. Among these cases, there were more men (n=1577; 52.3%) than women (n=1438; 47.7%). The average age at onset was 70.2±9.9 years (men 69.6±10.2; women 70.9±9.6), with 93.7% of the cases 55 years of age. Stroke subtypes were confirmed by CT/MRI neuroimaging in 2462 cases (81.7%). Nearly all patients (94.8%) were hospitalized for the condition. The proportion of ICH was the highest in Changsha (51.5%), followed by Shanghai (34.6%) and Beijing (26.7%). The characteristics of the study populations and registered first-ever stroke cases in the first and last year of follow-up are presented in Table 1.

    Incidence Rates of Stroke Subtypes

    The overall age-adjusted stroke incidence was the highest in Changsha (150.0 per 100 000 person-years; 95% CI, 141.3 to 160.0), followed by Beijing (135.0; 126.5 to 144.6) and Shanghai (76.1; 70.6 to 82.6; Table 2). Changsha also had the highest ICH incidence among the 3 cities, whereas Beijing had the highest rate in IS; interestingly, for both subtypes, Shanghai had the lowest rates. Generally, women had lower incidence of stroke than men, and similar geographic ranking in the incidence of stroke and its subtypes was found in both men and women. Additional information on the age-specific incidence of stroke and its major subtypes are presented in supplemental Tables I through IV, available online at http://stroke.ahajournals.org.

    The Figure compared the age-adjusted incidence for individuals 55 years of age in our study populations with that of other populations from published literature.10–22 The incidence of overall stroke and ICH was substantially higher in Beijing and Changsha than in Western populations.

    Age-adjusted incidence rates (per 100 000 person years) for first-ever-in-a-lifetime by stroke type in people 55 years of age from populations worldwide.

    Trends of Stroke Subtypes

    During the 1990s, ICH incidence decreased consistently in all 3 cities at an annual rate of 12.0% in Beijing, 4.4% in Shanghai, and 7.7% in Changhsha. In contrast, except for Changsha, the incidence of IS increased at 5.0% per year in Beijing and 7.7% in Shanghai (Table 3.

    Discussion

    Participants of this study included residents from 3 clearly geographically-defined urban communities with easy accesses to medical service in 3 large metropolitan cities of China. The Chinese traditional family structure with 3 generations living together made it possible for most stroke patients to be readily identified and sent to hospitals. Their neighbors were often notified and offered additional help. All possible stroke cases were initially identified through stroke report networks established in these communities, supplemented by annual door-to-door inquiries, and were subsequently confirmed by our study neurologists according to standard diagnostic criteria. The final diagnoses of stroke and its subtypes were uniformly made based on available clinical and neuroimaging information. Cases with death certificate only or identified only by CT/MRI during medical examinations without clinical symptoms and signs were excluded from the analysis after being reviewed by 3 participating neurologists. This alleviates some of our concerns that the increasing trend of IS was a result of increasingly used neuroimaging technology over years.

    Consistent with a previous report,23 we found stroke incidence was the highest in Changsha, followed by Beijing and Shanghai. Despite the general geographic gradient with a higher incidence of stroke in the north than south in China,1,24 there is evidence that the southern city of Changsha has an unexpectedly high rate of stroke incidence,3,23–24 and the reasons for this exception should be further investigated.

    Previous population-based studies found that 45.5% to 75.9% of all strokes in China were IS2 compared with 67.3% to 80.5% in Western countries,5 and the numbers for hemorrhagic stroke were 17.1% to 55.4% in China2,3 and 6.5% to 19.6% in Western populations.5 Consistent with these previous findings, the current study found that proportionally Chinese populations had relatively more hemorrhagic strokes and fewer ISs. These differences were also obvious when the incidence was compared. Compared with Western populations, the age-adjusted stroke incidence among individuals 55 years of age in Beijing and Changsha was among the highest reported; this was particularly true for hemorrhagic stroke. Interestingly, in all 3 cities, the incidence of hemorrhage stroke was decreasing and ischemic was increasing during the past decade, suggesting that the stroke subtypes of Chinese populations are rapidly adopting a Western pattern. Although genetic reasons could not be excluded in explaining the Chinese–Western difference in stroke incidence and compositions, our trend analysis indicates a role of environmental factors.

    With the economic booming in China, Chinese populations are rapidly adopting Western lifestyle and dietary habits, including increased energy intake, fat intake, and alcohol consumption, and decreased physical activity and cigarette smoking.25,26 These changes may have resulted in increased prevalence of obesity, hypertension, diabetes, and hypercholesterolemia in Chinese populations6,25 and may also help explain the increasing trend of IS as observed in this study. Uncontrolled hypertension and high prevalence of smoking might partially explain the hemorrhagic stroke predominance among Chinese in the past, and the increasing awareness of hypertension control and decrease in cigarette smoking26 may have contributed to its decrease in the past decade. On the other hand, the increasing prevalence of hypercholesterolemia, which is inversely associated with the risk of hemorrhagic stroke but positively associated with the risk of IS in eastern Asian populations,27 might have also contributed to the changing pattern of stroke subtypes.

    The use of neuroimaging techniques makes it easier to identify mild stroke cases and to accurately classify its subtypes. The increasing use of neuroimaging techniques in our study populations for stroke diagnosis may potentially contribute to the observed increase of IS incidence. However, this cannot explain the decreasing trend of hemorrhagic stroke. On the contrary, the simultaneously increasing use of neuroimaging and decreasing incidence of hemorrhagic stroke suggest a real decline in the incidence of hemorrhagic stroke.

    With the rapid aging of Chinese populations in the years to come, the public health burden associated with stroke will increase substantially. This will be accompanied by a Westernization of stroke subtype composition probably as a result of the adoption of Western diet and lifestyle by the Chinese. These behavioral changes will not only result in more IS but also may contribute to increasing incidence of other chronic diseases such as diabetes, cardiovascular diseases, and cancer. Therefore, there is an utmost urgency to face these challenges and to launch appropriate public health campaigns to prevent the occurrence of these chronic diseases.

    Acknowledgments

    This study was supported by funds from the National Scientific and Technical Committee and the Ministry of Health, People’s Republic of China. The serial numbers of grants were 85-916-01-03 (1991 to 1995) and 96-906-02-20 (1996 to 2000), respectively. H.C. was supported by the intramural program of the National Institute of Environmental Health Sciences.

    References

    Wu Z, Yao C, Zhao D, Wu G, Wang W, Liu J, Zeng Z, Wu Y. Sino-MONICA Project: a collaborative study on trends and determinants in cardiovascular diseases in China, part I: morbidity and mortality monitoring. Circulation. 2001; 103: 462–468.

    Zhang LF, Yang J, Hong Z, Yuan GG, Zhou BF, Zhao LC, Huang YN, Chen J, Wu YF. Proportion of different subtypes of stroke in China. Stroke. 2003; 34: 2091–2096.

    Yang QD, Niu Q, Zhou YH, Liu YH, Xu HW, Gu WP, Tian FF, Xie YQ, Zhang L, Xia J. Incidence of cerebral hemorrhage in the Changsha community. Cerebrovasc Dis. 2004; 17: 303–313.

    Tunstall-Pedoe H, editor. Prepared by Tunstall-Pedoe H, Kuulasmaa K, Tolonen H, Davidson M, Mendis S; with 64 other contributors for the WHO MONICA Project. MONICA Monograph and Multimedia Sourcebook. Geneva, Switzerland: World Health Organization; 2003. ISBN 92 4 156223 4 (NLM classification: WG 16).

    Feigin VL, Lawes CMM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol. 2003; 2: 43–53.

    Jiang B, Wang WZ, Wu SP, Du XL, Bao QJ. Effects of urban community intervention on 3-year survival and recurrence after first-ever stroke. Stroke. 2004; 35: 1242–1247.

    Li SC, Wu XG, Wang WZ, Wu SP, Gu DF, Xie LY, Yang QD, Zhou B, Liu YH. The basic design and method of community-based comprehensive prevention trial of cardio-cerebro-vascular diseases. Zhonghua Yu Fang Yi Xue Za Zhi (Chin J Prev Med). 1998; 32 (suppl): 5–7.

    Rosamod WD, Folsom AR, Chambless LE, Wang CH, McGovern PG, Howard G, Copper LS, Shahar E. Stroke incidence and survival among middle-aged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort. Stroke. 1999; 30: 736–743.

    Fay MP, Feuer EJ. Confidence intervals for directly standardized rates: a method based on the gamma distribution. Stat Med. 1997; 15: 791–801.

    Mihalka L, Smolanka V, Bulecza B, Mulesa S, Bereczki D. A population study of stroke in West Ukraine: incidence, stroke services, and 30-day case fatality. Stroke. 2001; 32: 2227–2231.

    Feigin VL, Wiebers DO, Nikitin YP, O’Fallon WM, Whisnant JP. Stroke epidemiology in Novosibirsk, Russia: a population-based study. Mayo Clin Proc. 1995; 70: 847–852.

    Morikawa Y, Nakagawa H, Naruse Y, Nishijo M, Miura K, Tabata M, Hirokawa W, Kagamimori S, Honda M, Yoshita K, Hayashi K. Trends in stroke incidence and acute case fatality in a Japanese rural area: the Oyabe Study. Stroke. 2000; 31: 1583–1587.

    Carolei A, Marini C, Napoli MD, Gianfilippo GD, Santalucia P, Baldassarre M, Matteis GD, Drio F. High stroke incidence in the prospective community-based L’Aquila registry (1994–1998): first year’s results. Stroke. 1997; 28: 2500–2506.

    Ellekjaer H, Holmen J, Indredavik B, Terent A. Epidemiology of stroke in Innherred, Norway, 1994 to 1996: incidence and 30-day case-fatality rate. Stroke. 1997; 28: 2180–2184.

    Lauria G, Gentile M, Fasseta G, Casetta I, Agnoli F, Andreotta G, Barp C, Caneve G, Cavallaro A, Cielo R, Mongillo D, Mosca M, Olivieri P. Incidence and prognosis of stroke in the Belluno province, Italy: first-year results of a community-based study. Stroke. 1995; 26: 1787–1793.

    Jorgensen HS, Plesner AM, Hubbe P, Larsen K. Marked increase of stroke incidence in men between 1972 and 1990 in Frederiksberg, Denmark. Stroke. 1992; 23: 1701–1704.

    Smadja D, Cabre P, May F, Fanon JL, Rene-Corail P, Riocreux C, Charpentier JC, Fournerie P, Saint-vil M, Ketterle J. ERMANCIA. Epidemiology of stroke in Martinique, French West Indies, part I: methodology, incidence, and 30-day case fatality rate. Stroke. 2001; 32: 2741–2747.

    Thrift AG, Dewey HM, Macdonell RAL, McNeil JJ, Donna GA. Incidence of the major stroke subtypes: initial findings from the Northeast Melbourne Stroke Incidence Study (NEMESIS). Stroke. 2001; 32: 1732–1738.

    Vemmos KN, Bots ML, Tsibouris PK, Zis VP, Grobbee DE, Stranjalis GS, Stamatelopoulos S. Stroke incidence and case fatality in southern Greece: the Arcadia stroke registry. Stroke. 1999; 30: 363–370.

    Corbin D, Poddar V, Hennis A, Gaskin A, Rambarat C, Wilks R, Wolfe C, Fraser H. Incidence and case fatality rates of first-ever stroke in a black Caribbean population: the Barbados register of strokes. Stroke. 2004; 35: 1254–1258.

    Kolominsky-Rabas PL, Sarti C, Heuschmann PU, Graf C, Siemonsen S, Neundoerfer B, Katalinic A, Lang E, Gassmann KG, Stockert TR. A prospective community-based study of stroke in Germany, the Erlangen stroke project (ESPro): incidence and case fatality at 1, 3, and 12 months. Stroke. 1998; 29: 2501–2506.

    Stewart JA, Dundas R, Howard RS, Rudd AG, Wolfe CDA. Ethnic differences in incidence of stroke: prospective study with stroke register. BMJ. 1999; 318: 967–971.

    Cheng XM, Ziegler DK, Lai Y-HC, Li SC, Jiang GX, Du XL, Wang WZ, Wu SP, Bao SG, Bao QJ. Stroke in China: 1986 through 1990. Stroke. 1995; 26: 1990–1994.

    He J, Klag MJ, Wu ZL, Whelton PK. Stroke in the People’s Republic of China: I, geographic variations in the incidence and risk factors. Stroke. 1995; 26: 2222–2227.

    Du SF, Lu B, Wang ZH, Zhai FY, Popkin BM. Transition of dietary pattern in China. Journal of Hygiene Research. 2001; 30: 221–225 (in Chinese).

    Jiang B, Wang WZ, Wu SP, Hong Z, Huang MS, Yang QD, Liu YH, Du XL, Bao QJ, Liu HM. Changes of both knowledge levels and health-related behaviors of preventing cardio-cerebro-vascular diseases in population after intervention. Journal of Hygiene Research. 2002; 31: 199–202 (in Chinese).

    Eastern Stroke and Coronary Heart Disease Collaborative Research Group. Blood pressure, cholesterol, and stroke in eastern Asia. Lancet. 1998; 352: 1801–1807.