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(Stroke. 1996;27:199-203.)
© 1996 American Heart Association, Inc.


Articles

Changed Incidence and Case-Fatality Rates of First-Ever Stroke Between 1970 and 1993 in Tartu, Estonia

Janika Kôrv, MD; Mai Roose, MD, PhD Ain-Elmar Kaasik, MD, PhD

From the Department of Neurology and Neurosurgery, University of Tartu (Estonia).


*    Abstract
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*Abstract
down arrowIntroduction
down arrowSubjects and Methods
down arrowResults
down arrowDiscussion
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Background and Purpose The incidence of stroke has stabilized or increased in several developed countries recently, but few data about the trends are available from Eastern Europe. The study was designed to evaluate the possible changes of stroke incidence in Estonia.

Methods A population-based stroke registry was conducted in Tartu during 1991 through 1993 (mean population, 110 631) to compare it with the study of 1970 through 1973 (population, 90 459). The majority of stroke patients were recorded prospectively, and most were hospitalized and evaluated by a neurologist. All available medical records were reviewed. Only first-ever stroke cases were registered.

Results A total of 667 patients in 1970 through 1973 and 829 patients in 1991 through 1993 were recorded. The total annual incidence per 100 000 rose from 221 to 250 (P=.0173). The total rate for men increased nonsignificantly from 183 to 209 and for women from 258 to 284. Significant increases were observed for men aged 50 to 59 years and for women aged 50 to 69 years; for persons over 70 years, the rates slightly declined. The case-fatality rate at 1 month declined significantly, from 49% to 30%.

Conclusions A remarkable increase in the incidence and decline in the case-fatality rate of first-ever stroke was observed in Tartu, Estonia. The increase of incidence for those younger than 70 years could be due to the increased prevalence of risk factors. The decline in case fatality could theoretically be related to better management of secondary complications.


Key Words: epidemiology • Estonia • incidence


*    Introduction
up arrowTop
up arrowAbstract
*Introduction
down arrowSubjects and Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Acute cerebrovascular diseases are the third leading cause of death in most developed countries. The mortality of stroke has decreased in most industrialized countries in recent decades,1 but in Eastern Europe the mortality rates continue to be high and even increased in some countries. Estonia, one of the three Baltic states, is experiencing an increase as well.2 The reasons for that unfavorable trend have remained unclear. Stroke mortality can decline or increase due to changes in incidence or changes in case-fatality rate over time, as well as changes in risk factors.3 Unfortunately, only a few incidence studies of stroke come from Eastern Europe4 5 6 ; only a recent study from East Germany has investigated the time trends,7 showing an increase in stroke incidence from the 1970s through the 1980s. Although some studies from developed countries have reported the fall in case fatality,8 9 10 the decline in the incidence of stroke has stopped, and some increase has become evident also in Rochester, Minnesota,8 in Denmark,11 and in Sweden12 during the 1980s. The register in Tartu was designed to evaluate the possible temporal changes of stroke incidence and case fatality in Estonia between 1970 and 1993.


*    Subjects and Methods
up arrowTop
up arrowAbstract
up arrowIntroduction
*Subjects and Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
A stroke registry was set up to evaluate and record all stroke patients in Tartu, Estonia, between January 1, 1991, and December 31, 1993, to compare the data with those from the earlier study carried out from January 1, 1970, through December 31, 1973.6

Study Area and Population
Tartu is a university town situated in the eastern part of Estonia. The mean population of Tartu was 90 459 (based on the 1970 census) in 1970 through 1973 and 110 631 in 1991 through 1993 (1989 census). The older age group (over 70 years) constituted 7% of the whole population during the first and 8% during the second study. The age and sex distributions of Tartu, which is the second largest town in Estonia, quite precisely approximate those of the whole country. Most of the population are ethnic Estonians, although genetically rather mixed.

Case Ascertainment
The study area is served by the Department of Neurology and Neurosurgery (DNN) of the University Hospital of Tartu, by five specialized hospitals, and by an outpatient clinic. During the study, the healthcare system in Estonia was quite strict, and the possibility of treating stroke patients outside the study area was minimal. The proportion of neurologists in Tartu is high, and qualified medical care is readily available to the population. Most acute stroke patients in Tartu are routinely admitted to the DNN of Tartu University Hospital.

The studies were carried out using similar case-finding methods and diagnostic criteria. All stroke patients admitted to the DNN were evaluated as soon as possible by the members of the study group, and the first-ever cases were registered. Every available source (interviewing the patients and their relatives, tracing information from their outpatient and hospital records) was used to obtain information about the case history and comorbid diseases.

The stroke patients staying at home were provided with medical attention at the outpatient clinic. As a rule, most patients treated at home are examined by a neurologist in Tartu. Before the study started, all neurologists in Tartu were informed about the project, and they were asked to send all stroke patients to the DNN. During 1970 through 1973, the nonhospitalized patients were identified by checking the home-call registers and through personal contacts; during the recent study, they were identified with the help of a computerized home-call register kept for health statistics in the outpatient clinic. The cases were searched for and retrieved under codes 430 to 436 of the International Classification of Disease (from records containing the patient's name, address, diagnosis, doctor's name, and date). All outpatient records of suspected first-ever stroke were reviewed, and those meeting the diagnostic criteria were registered. Additionally, the neurologists of the outpatient clinic were personally contacted as necessary.

Most of the stroke patients whose strokes occur while they are inpatients in other departments of the Tartu University Hospital and other hospitals of Tartu are routinely evaluated by the consulting neurologists of the DNN. In 1970-1973, the stroke cases were identified mainly through personal contacts with consulting neurologists. During the recent study, the information was retrieved from the computerized registers kept at the hospitals, identical to those of the outpatient clinic. Additionally, the discharge lists of other departments and hospitals were checked once a month during both study periods.

The general practitioner at the nursing home was notified of the register, and all acute stroke patients were evaluated by one of the authors. Milder stroke patients were taken to the DNN for more precise examination, and more severe patients were treated at the nursing home. The records from smaller hospitals around the town were reviewed to find cases of stroke among permanent residents of Tartu who might have been admitted to these institutions.

Death certificates and autopsy protocols for fatal cases outside the hospital were regularly checked; in the case of a clinical diagnosis of stroke, clinical records were reviewed. Only cases with definite clinical diagnosis of stroke were included. All more complicated stroke cases causing diagnostic problems were discussed at the regular meetings of our study group. In addition, all available information from outpatients' records was collected, especially about the patients who were not personally contacted to verify the diagnosis and case history.

The patients were followed up with a questionnaire sent to them after 6 months and by checking their data from the Address Bureau of Estonia after 1 year.

Diagnostic Criteria
The diagnosis of stroke was based on clinical evaluation using the World Health Organization (WHO) criteria, defined as "rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than vascular origin." We registered all first-ever stroke cases and transient ischemic attacks, but only first-ever stroke cases were considered when calculating the incidence. First-ever cases were defined as those occurring for the first time during the patient's lifetime.

In 1970-1973, the subtypes of stroke were classified at first by autopsy, secondarily by lumbar puncture, and finally by clinical evaluation.

During the second study period, the subtyping of stroke was primarily based on autopsy, CT, or MRI, secondarily on lumbar puncture, and last on clinical examination. The data on stroke subtypes will be discussed subsequently.

Statistical Methods
The data are presented in 10-year age groups (starting from 0 to 49 years, 50 to 59 years, etc) as was done previously.6 Unfortunately, the original data file of the first study period was not available for technical reasons; therefore, we were not able to present the data using standard age groups. For cross-national comparisons, the data will be reported in a following article. The incidence rates were age- and sex-adjusted by the direct method to the average population of the last study and to the 1990 Estonian population. The 95% confidence intervals (CIs) were calculated by the standard method based on Poisson distribution. The Cochran-Mantel-Haenszel z test, stratified by age when appropriate, and the {chi}2 test were used when analyzing the difference between two groups; P<.05 was considered significant. The statistical analysis was performed with the Statistica program.13


*    Results
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up arrowSubjects and Methods
*Results
down arrowDiscussion
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Altogether, 1496 first-ever stroke cases were registered during the study periods (667 in the first and 829 in the second period). The mean age of patients for both studies was 70 years. The mean age for men was 63 years for the first and 64 years for the second period; for women it was 74 years for the first and 73 years for the second period.

Of patients admitted to the DNN, 34% were admitted during 1970-1973 and 72% during 1991-1993. In the second period, 158 patients (19%) were cared for at home. As a rule, in the early 1970s only the patients below the age of 60 years were routinely admitted with acute stroke. However, in addition to the patients admitted to the DNN, almost all patients treated at home were personally evaluated by the study neurologist. The diagnosis was verified at autopsy in 137 cases (21%) and supported by lumbar puncture in 126 cases (19%) in 1970-1973. The rest of the patients were evaluated only clinically.

In 1991-1993, the diagnosis was first based on autopsy in 68 cases (8%) and on CT or MRI on 157 cases (19%). In 323 cases (39%), the diagnosis was based on lumbar puncture and finally in 281 cases (34%) on clinical diagnosis. Seventy-nine patients of the latter group (28%) were seen only by a general practitioner and 3 (1%) by an ambulance doctor. In total, the patients were evaluated by a neurologist in 737 cases (89%).

Incidence of Stroke
The total age-adjusted (to the 1991-1993 population of Tartu) incidence rate of first-ever stroke increased significantly from 221 to 250 per 100 000 annually (Table 1Down). The total age-adjusted rate for men increased from 183 to 209 (Table 2Down) and for women from 258 to 284 (Table 3Down), but the changes were not significant. For men, the increment of incidence rates was limited to those <70 years: for age groups 0 to 49 and 60 to 69 years it was nonsignificant, whereas the age group 50 to 59 years showed an increase of 231%. For older men (>=70 years), the incidence rates were somewhat lower during the recent study period. In women, the changes followed a similar pattern: the incidence rise in women occurred solely due to the increase in younger women. A statistically significant increase became evident in the age groups 50 to 59 and 60 to 69 years; for the youngest group the rise was quite slight. For older women, by contrast, the rates during the recent study did not change. For both studies, the age-specific incidence rates increased steeply with age. After adjustment by age and sex, the rate for men in 1970-1973 was a third higher (P<.0001) than that for women: 262 (95% CI, 226 to 298) and 201 (95% CI, 182 to 221), respectively. During 1991-1993, the incidence rate for men (274; 95% CI, 243 to 305) was a fifth higher (P<.001) than that for women (227; 95% CI, 207 to 247).


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Table 1. Age-Specific Incidence Rates of First-Ever Stroke for Both Sexes (Per 100 000 Annually) in Tartu, Estonia


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[in a new window]
 
Table 2. Age-Specific Incidence Rates of First-Ever Stroke for Men (Per 100 000 Annually) in Tartu, Estonia


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Table 3. Age-Specific Incidence Rates of First-Ever Stroke for Women (Per 100 000 Annually) in Tartu, Estonia

After adjustment by age and sex to the 1990 Estonian population, the incidence rates for 1970-1973 were 214 (95% CI, 197 to 230) for both sexes combined, 254 (95% CI, 219 to 288) for men, and 194 (95% CI, 157 to 212) for women. The corresponding rates in 1991-1993 were 244 (95% CI, 227 to 261) for all, 269 (95% CI, 239 to 299) for men, and 221 (95% CI, 201 to 240) for women.

Case-Fatality Rates
The case fatality of first-ever stroke at 30 days was 49.2% (95% CI, 44.1 to 54.8) during the first period and 30.2% (95% CI, 26.6 to 34.1) during the second period. Between the studies, the total case-fatality rate at 1 month significantly decreased ({chi}2=56.39, P<.0001).


*    Discussion
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowSubjects and Methods
up arrowResults
*Discussion
down arrowReferences
 
A remarkable increase of the incidence of first-ever stroke has occurred between 1970-1973 and 1991-1993 in Tartu, Estonia. The rise occurred solely due to the significant increase of the rates in people younger than 70 years. The most pronounced increases were observed for the age groups 50 to 59 years in men and 50 to 69 years in women. The declining trend for those older than 70 years was rather mild and appeared exclusively in older men. In older women, the rates were unchanged. The age-adjusted incidence rates were higher for women than for men. As for the whole population of Tartu, in older age groups (>=70 years) the female-to-male ratio was 3.1 in 1970-1973 and 2.5 in 1991-1993. Hence, after adjustment for age and sex, a significant predominance for men during the studies remained stable. Although the total incidence rates increased, the case fatality at 30 days decreased significantly.

When designing an incidence study, several criteria should be met for the study to be considered "ideal."14 Besides several others, two important factors for an ideal study are complete case ascertainment and accurate diagnosis of stroke, especially among the elderly who may not be admitted or may even die before seeing a physician. Generally, the traditions of Tartu University Hospital go back to the 1920s and influence the whole healthcare system of Tartu; the high proportion of neurologists and the readily available qualified health care considerably facilitate the case ascertainment in Tartu. Stroke patients staying at home and not contacting the doctor, mainly with mild stroke, represent a potential source of bias in most population-based studies.15 During the studies, we made special efforts to identify all nonhospitalized cases and the cases from other hospitals with overlapping methods. More complicated stroke cases were discussed in detail at our meetings. However, if some cases remained unregistered (probably among the elderly), it is unlikely that this shortcoming was limited to the second period only. We believe that these few possible missed cases probably did not affect the total incidence numbers. Because of the similar case-finding systems used in the studies, we assume that the decreased rate in older men during the recent period was not due to a systematic mistake of selectively missing more cases in older men than women. Furthermore, the incidence rates for older women were comparatively stable between the periods.

In the 1970s, before the era of CT, most stroke cases were verified primarily by autopsy, secondarily supported by lumbar puncture, and finally evaluated by clinical examination. In Estonia, CT was introduced in the middle of the 1980s and has been more routinely used for the evaluation of stroke patients since 1993. Although the proportion of CT in 1991-1993 was relatively low, one might suspect that the incidence increased because of more successful case ascertainment with CT during the second study. A recent study from Rochester supports the impact of CT on case ascertainment.8 In Rochester, the incidence rates stabilized and even increased with the concomitant fall of the case-fatality rate, presumably due to the better detection of milder cases in the 1980s. Similar to others, our study excluded the cases identified only by CT,7 10 11 and the diagnosis of stroke was based strictly on the WHO clinical definition.

At first sight, the noteworthy decrease in case-fatality rate between the studies could be due to the inclusion of milder cases in 1991-1993 that might have remained unregistered in 1970-1973. These omitted cases could have reduced the case-fatality rate. The fact that both studies were designed to identify all transient ischemic attack cases in addition to strokes to prevent mild strokes from confounding with transient ischemic attack speaks against that argument. Another source of artificial decline of the case-fatality rate could be the possibly unregistered severe stroke cases in 1991-1993, since some older stroke patients might not have sought medical care at all before they died and could have been omitted from the register. The fact that health services are readily available and free for the population probably diminished the latter possibility to very few cases. However, we did not make a point of blind recording the data because one of the authors of the previous study (M.R.) participated in the last study also, and all cases of patients found unconscious were discussed. In addition, we used several overlapping methods, and we believe that the case ascertainment system was accurate.

The available data from population-based studies show that the trends of stroke incidence in different age-specific groups are not similar between the studies. A recent study from East Germany7 reported an increase of first-ever stroke in men in all age groups from 25 to 74 years. In women between the ages of 55 and 64 years, the rates significantly declined; in age groups 25 to 54 and 65 to 74 years, the rates increased. Unfortunately, the population older than 75 years of age, in whom the majority of stroke cases occur, was not included in the study. The increasing rates could be associated with deteriorating lifestyle factors among the population of East Germany, especially in men. A Danish study11 comparing two registers of Frederiksberg from 1972 through 1974 and 1989 through 1990 reported an increasing incidence in men aged 65 to 84 years concurrent with increased treatment of hypertension in the whole country. The authors supposed that the increased incidence of stroke in men might be followed by increased rates in women. The previous study from Tartu6 found crude incidence rates for 1970-1973 (184/100 000) similar to those in Rochester (194/100 000) for 1945 to 1954,16 but the changes over several decades have been completely different. In Rochester, the incidence rates experienced a decline of 46% between 1950 and 1979 and a 17% rise in 1980 through 1984 compared with the previous quinquennium. The rates changed markedly for the oldest age groups. Unfortunately, no information about the secular trends of stroke incidence is available for Tartu, but at present the total incidence rate of Tartu greatly exceeds that of Rochester.

Our data reflecting decreased incidence rates in the elderly are quite similar to those from a recent study from Auckland,10 where the rates in women younger than 75 years rose by a fifth; in younger men the rise was nonsignificant. In older men (over 75 years) rates fell by a third, while the rates for older women declined only slightly. Furthermore, the decline in case fatality within 1 month was noted as well. In contrast, in Söderhamn, Sweden,12 comparison of the 1-month death rates from 1975 through 1978 and 1983 through 1986 showed no trend. The study reported an increase of the total rate for women of 38%, which occurred mainly because of the increase of incidence in middle-aged women. For both men and women older than 85 years, the rates somewhat increased. No clear reason for the rise is given, although it is assumed to be affected by changes in risk factor levels. Another Swedish study conducted in Göteborg from 1971 through 19879 based on registration of first-ever stroke among the population 15 to 64 years of age found no change in the incidence, but there was a decline in case-fatality rates.

The decrease of the rates in men older than 20 years in Tartu might be associated with the fact that "stroke-prone persons" die of ischemic heart disease before they reach the age at which they would have a stroke.17

This assumption is in line with the increase in mortality from ischemic heart disease and myocardial infarction according to the official statistics.2 Another possible explanation might be that the first stroke is occurring at younger ages, especially in men.

The increased stroke incidence in younger men and women is not easy to explain. It is unlikely that the rise is due to the decrease of coronary heart disease, since no decrease of that disease has been documented in Estonia.

Change in the effects of risk factors is one of the major determinants that influence incidence rates directly or case fatality indirectly by influencing the natural history of the disease.3

In most parts of the world, the population risk-factor levels have generally declined. By contrast, limited data suggest that risk-factor levels in Eastern Europe are worsening.18 The data on cardiovascular risk-factor levels in Estonia are scarce, but those available show high blood pressure levels among the middle-aged population and high prevalences of cigarette smoking and a cholesterol-rich diet.19 According to the risk-factor survey in the 1980s of all WHO MONICA project centers,20 the mean levels of known cardiovascular risk factors in Kaunas, Lithuania, were high and probably related to the high incidence and mortality rates of stroke.4 This coincides with our findings of high incidence and mortality, and we suspect that the risk-factor levels in Estonia might not be very different from those in Lithuania, another Baltic state that regained its independence recently. Speculation leads us to conclude that in Estonia the undetected and untreated hypertension, cigarette smoking, and heavy alcohol use are a greater problem in the young and the middle-aged than among the elderly. Other factors, such as poor socioeconomic level and severe psychoemotional stress, that were assumed to influence the stroke incidence in other studies9 21 probably play a role among the population of Estonia as well. In contrast, the decline of the incidence among the elderly and the decline of the case-fatality rate for all might theoretically be associated with the more active prestroke treatment of hypertension introduced in Estonia in the 1970s. Part of the stroke decline in Rochester in the 1960s and 1970s was probably related to the decreasing prevalence of hypertension, particularly for persons >=75 years.22 Although no evidence exists about the real situation of the treatment of high blood pressure in Tartu, the decrease in incidence for the oldest group between the studies could be explained by more adequately controlled hypertension in the elderly than in younger age groups. Thus, the risk factors of stroke and their trends in Estonia would need further research.

The decline in case-fatality rates might be associated with changes in the natural history of stroke or better management of stroke in the acute stage. Verification of the former possibility needs more precise measures of changes in the severity of the disease. As for the management of stroke, the early mortality of stroke depends predominantly on the prevention of secondary complications rather than on the direct therapeutic effect on acute brain damage.8 23 We speculate that the case-fatality rate might have declined because of the shift toward more effective intensive care during the acute period of stroke in Tartu, and we possibly succeeded in avoiding these complications. Also, the proportion of hospitalization to the special neurological and neurosurgical services rose from 34% to 72%, respectively, during the first and second study. Compared with other studies,8 9 10 12 15 the early case-fatality rate is high.

In conclusion, the finding of increased incidence rates and considerably high case-fatality rates in 1991-1993 is in accordance with the high mortality numbers for cerebrovascular diseases found in Estonia. We have to be concerned about the increased incidence in the younger and middle-aged population and pleased about the decreased incidence among the elderly. As suggested by other investigators,7 8 9 10 11 12 the trend of stroke incidence for the next century will not be very positive. Nevertheless, the data on risk-factor levels for stroke are scarce, and the information about the trends of these levels is missing in Estonia. The results of this study demonstrate the need for more effective primary prevention of stroke, especially among the younger population.


*    Acknowledgments
 
This study was supported by a grant from the Estonian Science Foundation.


*    Footnotes
 
Reprint requests to Janika Kôrv, MD, Department of Neurology and Neurosurgery, University of Tartu, 2 L Puusepp St, EE2400 Tartu, Estonia. E-mail Janika@cut.ee.

Received August 8, 1995; revision received October 24, 1995; accepted October 26, 1995.


*    References
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up arrowAbstract
up arrowIntroduction
up arrowSubjects and Methods
up arrowResults
up arrowDiscussion
*References
 

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  11. Jørgensen HS, Plesner A, Hübbe P, Larsen K. Marked increase of stroke incidence in men between 1972 and 1990 in Frederiksberg, Denmark. Stroke. 1992;23:1701-1704. [Abstract/Free Full Text]
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Stroke in Lund-Orup, Sweden: Improved Long-Term Survival Among Elderly Stroke Patients
Stroke, June 1, 2002; 33(6): 1624 - 1629.
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B. Johansson, B. Norrving, and A. Lindgren
Increased Stroke Incidence in Lund-Orup, Sweden, Between 1983 to 1985 and 1993 to 1995
Stroke, February 1, 2000; 31(2): 481 - 486.
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P. Thorvaldsen, M. Davidsen, H. Bronnum-Hansen, and M. Schroll
Stable Stroke Occurrence Despite Incidence Reduction in an Aging Population : Stroke Trends in the Danish Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Population
Stroke, December 1, 1999; 30(12): 2529 - 2534.
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