Stroke Incidence, Case Fatality, and Mortality in the WHO MONICA Project
Background and Purpose This report compares stroke incidence, case fatality, and mortality rates during the first years of the WHO MONICA Project in 16 European and 2 Asian populations.
Methods In the stroke component of the WHO MONICA Project, stroke registers were established with uniform and standardized rules for case ascertainment and validation of events.
Results A total of 13 597 stroke events were registered from 1985 through 1987 in a total background population of 2.9 million people aged 35 to 64 years. Age-standardized stroke incidence rates per 100 000 varied from 101 to 285 in men and from 47 to 198 in women. The combined stroke attack rates for first and recurrent events were approximately 20% higher than incidence rates in most populations and varied to the same extent. Stroke incidence rates were very high among the population of Finnish men tested. The incidence of stroke was, in general, higher among populations in eastern than in western Europe. It was also relatively high in the Chinese population studied, particularly among women. The case-fatality rates at 28 days varied from 15% to 49% among men and from 18% to 57% among women. In half of the populations studied, there were only minor differences between official stroke mortality rates and rates measured on the basis of fatal events registered and validated for the WHO MONICA stroke study.
Conclusions The WHO MONICA Project provides a unique opportunity to perform cross-sectional and longitudinal comparisons of stroke epidemiology in many populations. The present data show how large differences in stroke incidence and case-fatality rates contribute to the more than threefold differences in stroke mortality rates among populations.
The WHO MONICA (World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease) Project1 2 was initiated in the early 1980s. The aim was to continuously register the occurrence of myocardial infarction and stroke among many populations and to analyze the relation between temporal trends in incidence and mortality rates and changes in major cardiovascular risk factors over time. By use of uniform procedures and methods, stroke event rates were monitored for a 10-year period. Core data for each event were collected and analyzed at the WHO MONICA Data Center in Helsinki, Finland.
In stroke epidemiology, official mortality statistics have long been the most commonly used source for multinational comparisons,3 4 5 6 7 and they are still the source that permits comparisons across the most countries and continents. But the validity of routine statistics has been questioned. Death-certificate coding may vary between countries, and because case-fatality rates vary8 the numbers of cerebrovascular deaths do not uniformly reflect the numbers of stroke survivors and the total burden of stroke in a population.
Stroke registers can provide more accurate estimates of incidence and mortality rates than official routine statistics.9 Data on stroke incidence are widely available10 from community-based stroke studies11 12 13 14 15 and cohort studies16 17 in many countries. These have contributed valuable information on temporal trends within the populations under study, but differences in study design limit the possibilities for comparisons across populations. Exceptions to this are the WHO collaborative study on stroke in the community18 and more recent studies with WHO MONICA criteria for case ascertainment and classification of stroke events.19 20 21 22 23 24
This article compares stroke incidence, case fatality, and mortality rates at baseline among 18 populations in 10 countries for the WHO MONICA Project.
Subjects and Methods
Between 1982 and 1986, 19 of 39 MONICA Collaborating Centers (MCCs) entered the stroke component of the MONICA Project. Four MCCs withdrew from the stroke study after a few years of registration, mainly because of lack of funding and failure to ensure complete coverage. Since some of the remaining 15 MCCs cover more than one study population, the stroke component of the WHO MONICA Project involves 21 populations in 11 countries. Data from three populations (two in Hungary and one in Russia) were omitted from the present comparison because validations of case ascertainment were not completed by the time the data were compiled.
Table 1⇓ shows the average midyear population of men and women aged 35 to 64 years, obtained from population registers, censuses, or intercensus estimates for calendar years 1985 through 1987. The total study population was 2.9 million people. Detailed information on how MONICA populations are defined is given elsewhere.1 2
The protocol for the stroke registers provided detailed instructions for event registration. It included guidelines for case ascertainment, outlined validation procedures, and gave specific coding rules for diagnostic category (definite stroke, unclassifiable, or not stroke), order of event (first or recurrent), and case-fatality rate. Local validations of registration procedures were undertaken because registrations were implemented within widely different health services systems, and, thus, adjustments were required locally by practical, ethical, and medicolegal demands.
Definitions of Stroke and Diagnostic Categories
Stroke was defined as rapidly developed signs of focal (or global) disturbance of cerebral function lasting >24 hours (unless interrupted by surgery or death), with no apparent nonvascular cause; this category included patients presenting with clinical signs and symptoms suggestive of subarachnoid hemorrhage, intracerebral hemorrhage, or cerebral ischemic infarction. Hence, the study is based on clinical diagnoses, which have been shown to be reliable.25 During the years covered by this report, diagnostic procedures permitting valid classification of stroke subtypes (eg, neuroimaging) were available to only a limited extent in several populations and not at all in some.
The WHO MONICA Project is concerned with events, not persons. Events are classified as first or recurrent and as fatal or nonfatal. A period of 28 days was used to define the case-fatality rate and to distinguish between events. Diagnostic criteria were applied to symptoms, clinical findings, and investigations undertaken within 28 days of onset. Transient ischemic attacks and silent brain infarctions (cases without clinical symptoms or signs) were not included. Neither were events associated with trauma, blood disease, or malignancy.
Events were categorized as “definite stroke,” “not stroke,” or “unclassifiable.” Criteria for definite stroke were fulfilled when the available information permitted a clinical diagnosis of stroke. Unclassifiable was used when no diagnosis other than stroke was present to explain the event but the available information was insufficient for determining whether symptoms and duration fully met the MONICA criteria for definite stroke. The term unclassifiable was, with few exceptions, restricted to fatal events.
All events that occurred in the study population were registered and assigned to a diagnostic category, irrespective of survival status and place of occurrence and management. Death certificates were the major source of identification for fatal events. All death certificates with an International Classification of Diseases (ICD) code of 430 to 434 or 436 were registered and validated according to MONICA criteria. The MCCs used the eighth or ninth revised version of the ICD; both these versions use the same codes for acute cerebrovascular diseases, including codes for subarachnoid hemorrhage, intracerebral hemorrhage, thromboembolic ischemic brain infarction, and ill-defined stroke. In most centers, death certificates within a wider range of ICD codes were scrutinized because diagnoses other than acute stroke also indicated stroke events categorized as definite or unclassifiable according to MONICA criteria.
Hospitalized patients were identified from hospital admission lists (“hot pursuit”) or discharge diagnoses (“cold pursuit”). All ICD codes from 430 to 434 and code 436 were searched and validated. A wider range of diagnoses was required for the initial part of the study; diagnoses that did not contribute to the registration were subsequently omitted from the search profile.
Events were validated on the basis of medical records specific to the admission relating to the event. Records from previous admissions, outpatient clinics, and other medical services were scrutinized when available and pertinent to the determination of diagnostic category or order of event.
For identification and validation of cases managed outside the hospital, various procedures adjusted to conform with local conditions were applied. The main source of information was general practitioners, who reported cases managed at home or in institutions other than hospitals, either spontaneously or on request from the MONICA team.
The term “stroke attack rate” refers to both first and recurrent events (all strokes), whereas “incidence rate” is restricted to only the first stroke. “Case fatality rate” is defined as the proportion of events that are fatal within 28 days of onset. “Mortality rate” is the number of fatal events that occurs within 28 days per a population of 100 000 people.
Age-standardized stroke attack, incidence, and mortality rates were calculated on the basis of patients ranging from 35 to 64 years old divided into groups according to age (5 years per group): 35 to 39, 40 to 44, 45 to 49, 50 to 54, 55 to 59, and 60 to 64 years old. Weights of 6, 6, 6, 5, 4, and 4, respectively, were derived for each group from the age distribution of Segi’s world population.26
Age-standardized case-fatality rates were calculated on the basis of 10-year age groups of 35 to 44, 45 to 54, and 55 to 64 years old, with weights of 1, 3, and 7, respectively, reflecting the age distribution of all stroke events. Confidence intervals were calculated with the relation between Poisson and χ2 distributions to derive confidence intervals for weighted sums of Poisson parameters.27
For this article, small study populations in some MCCs were combined to obtain sufficiently large numbers of events for stable descriptive statistics.
A range of quality-control measures for data collection procedures and coding practices was introduced. Series of test-case histories were circulated and completed by the MCCs for evaluation of coding practice.28 Data submitted to the MONICA Data Center were checked for completeness, logical consistency, and deviant distributions of key variables. Registration of fatal events was assessed for completeness by comparison with official mortality statistics for the MONICA populations. No uniform external source was available for nonfatal events. Assessment of the completeness of registration included detailed checking and explanations of any deviant distributions from the MCCs concerned. Details of the data quality assessment have been reported elsewhere.29
In men and women aged 35 to 64 years, 13 597 total definite and unclassifiable stroke events occurred from 1985 to 1987. The numbers of events by sex and population and the percentages of events classified as definite, recurrent, or fatal are shown in Table 2⇓.
Overall, <1% of all nonfatal events was unclassifiable. This proportion did not exceed 5% in any population, and in 11 populations no such events were recorded. The proportion of unclassifiable fatal events was >10% in populations from the former East Germany (German Democratic Republic) and West Germany (Federal Republic of Germany) and was as much as one fifth in the Warsaw, Poland, and both Moscow, Russian Federation, populations. In the remaining populations, this proportion was <10%.
The median proportion of recurrent stroke among populations was 20%, ranging from 8% in Göteborg, Sweden, to 26% in Beijing, China (Table 2⇑). In nine MONICA populations, this proportion was between 18% and 22%. The proportion of nonfatal events of unknown order (first or recurrent) was <2% on average and <5% in all populations. Approximately one third of the fatal events were of unknown order among the Göteborg population, the two Moscow populations, and the Warsaw population, but this proportion did not exceed one fifth in the remaining 14 populations.
The average annual stroke attack rates for first and recurrent strokes are shown in Table 3⇓. There was a threefold differential among men in the population with the highest stroke attack rate (Kuopio, Finland) versus those in the population with the lowest stroke attack rate (Friuli, Italy). In women, the stroke attack rate was five times higher in the population from Novosibirsk, Russian Federation, than that from the Rhein-Neckar region of Germany (formerly part of West Germany). If the Novosibirsk population is disregarded, the variation among populations was the same for men and women. In general, stroke attack rates were lower in western than in eastern Europe for both men and women.
Fig 1⇓ shows age-standardized incidence rates for definite first occurrences of stroke. The range of variation for incidence rates between populations and geographical distribution was not substantially different from that of stroke attack rates.
Stroke attack and incidence rates were higher among men than women in all populations. The ratio of men to women for age-standardized incidence rates varied from 1.2 in Novosibirsk to 2.4 in North Karelia, Finland. In six populations, the rates among men were more than twice those among women.
Table 4⇓ shows incidence rates for definite stroke according to 10-year age groups, population, and sex. Stroke incidence rates increased steeply with age in all populations.
The average case-fatality rate at 28 days was 30% and varied threefold among populations, ranging from 15% to 49% among men and from 18% to 57% among women (Table 2⇑). The lowest case-fatality rates were reported from populations in the Nordic countries (Denmark, Finland, and Sweden), West Germany, Lithuania, and Novosibirsk, Russian Federation, whereas case-fatality rates were high in most of the eastern European populations (that of Warsaw, Poland, in particular) and in Italy. Case fatality rates were higher among women than men in all populations except the Kaunas, Lithuania, and the Novosibirsk populations.
Data submitted to the MONICA Data Center included the official numbers of cerebrovascular deaths (ICD codes 430 to 438), which were derived from routine statistics and reported by population, sex, and age group.
Age-standardized mortality rates calculated on the basis of fatal events validated and registered for the WHO MONICA Project were similar to official routine mortality rates for the same age ranges among most MONICA populations (Fig 2⇓). In some populations, the official mortality rates were notably higher than the rates based on MONICA criteria. Among the three MONICA populations in the former East Germany, official mortality rates were lower than those derived by use of MONICA criteria.
The present cross-sectional study, done at baseline for the WHO MONICA Project, has demonstrated differences in stroke incidence and case-fatality rates of greater than threefold between populations. This study also has shown that official mortality statistics on stroke are reliable in several countries. Our observations support the observations of marked variations in stroke mortality rates reported in previous multinational comparisons.
The present study comprises only two populations outside Europe and is therefore geographically more limited than the previous WHO study on stroke18 and other comparisons of stroke incidence10 and of official mortality statistics.3 4 5 6 7 Within the present geographic range, a pattern is recognized, with very high attack, incidence, and mortality rates among the Finnish population studied and with higher attack, incidence, and mortality rates among the populations of eastern Europe than among those in western Europe. These results agree with those from studies of stroke mortality based on routine statistics, and the geographic distribution for these rates resembles that for rates of coronary heart disease morbidity and mortality.30
High 28-day case-fatality rates combined with relatively low stroke attack rates were seen in two populations (those in Warsaw, Poland, and Friuli, Italy) suggesting incomplete coverage of nonfatal cases. However, detailed validations in both centers failed to document substantial numbers of events not ascertained by the WHO MONICA registers.29
Death certificates were scrutinized in all populations. In addition to this, sources identifying the stroke onset (eg, hospital records) also indicated fatal events. Consequently, the registration of fatal events was probably less sensitive to differences among case-finding procedures, since many such events were retrievable from more than one source. On the other hand, fatal events were more often than nonfatal events unclassifiable or of unknown order. Thus, the precision of the estimates for fatal events was influenced by the quality of the available information, whereas the estimates of nonfatal events were more sensitive to case ascertainment procedures per se.
In several populations, the stroke mortality rate calculated from official routine statistics was higher than that measured by the stroke registers. This may be due in part to more deaths being attributed to cerebrovascular disease (stroke or late sequelae of stroke) after the 28th day of stroke onset or to an excess number of cases that for other reasons did not fulfill MONICA criteria for stroke. Obviously, less-specific criteria will permit a larger contingency. This may be of particular relevance for the high mortality figures previously reported from the population in China. In China, autopsy is rarely performed (WHO MONICA Project, unpublished data, 1994); as a consequence, stroke deaths may be overestimated by official routine statistics for the Chinese population. Similar discrepancies between official mortality statistics and WHO MONICA stroke register data seem to be present for populations in the Russian Federation and the former Yugoslavia. In one country, the former East Germany, the contrary was observed; routine statistics underestimated the true number of stroke deaths. Among most MONICA populations, however, there was very good agreement between mortality rates by official statistics versus the stroke registers. Thus, official mortality statistics may be used for comparisons of international populations in which validation has been undertaken.
The case-fatality rate at 28 days varied markedly (threefold) between populations. Whether this variation is due to differences in case ascertainment, stroke severity, or the result of different management of acute stroke cannot be answered by the present data. The relative frequency of stroke subtypes will influence the overall case-fatality rates, since cerebral hemorrhage is fatal more often than is ischemic brain infarction.12 However, the present data do not permit analyses of stroke subtypes. Future analyses of more recent MONICA Project stroke data and from selected populations may help clarify this issue. Such analyses may also help clarify whether differences in medical services available to men versus women contribute to the consistently higher case-fatality rate among women in the MONICA populations.
The stroke component of the WHO MONICA project was optional, and only half of all MCCs established registers to monitor stroke events in addition to coronary events. Thus, the present study covers mainly European populations of middle-aged subjects. Despite these limitations, the WHO MONICA Project provides a unique opportunity to perform cross-sectional and longitudinal comparisons of stroke epidemiology among many populations, and, once completed, the study will have compiled data on what is probably the most stroke events ascertained in a comparable manner in recent years.
Sites and Key Personnel of Contributing MONICA Centers
China. Beijing Heart, Lung, and Blood Vessel Research Institute: Wu Zhaosu (Principal Investigator) and Wu Yingkai (Former Principal Investigator).
Denmark. Glostrup Population Studies, Glostrup University Hospital: M. Schroll (Principal Investigator), H. Kirkby, S. Henriksen, D. Jeppesen, G. Vincents, and P. Thorvaldsen.
Finland. National Public Health Institute, Helsinki: E. Kaarsalo, E.V. Narva, T. Nuottimäki, P. Puska (Former Principal Investigator), K. Salmi, V. Salomaa, C. Sarti, J. Sivenius, J. Torppa, and J. Tuomilehto (Principal Investigator).
Germany. Department of Clinical and Social Medicine, University Medical Clinic, Heidelberg: E. Nüssel (Principal Investigator) and E. Ostör-Lamm (Co-Principal Investigator); Centre for Epidemiology and Health Research, Berlin: W. Barth (Principal Investigator), L. Heinemann (Principal Investigator), and D. Eisenblätter.
Italy. Institute of Cardiology, Regional Hospital, Udine: G.A. Feruglio (Principal Investigator).
Lithuania. Institute of Cardiology, Kaunas Medical Academy: J. Bluzhas (Principal Investigator).
Poland. Department of Cardiovascular Epidemiology and Prevention, National Institute of Cardiology, Warsaw: S.L. Ryvik (Principal Investigator), M. Polakowska (Co-Principal Investigator), G. Broda (Co-Principal Investigator), B. Jasinski (Responsible Officer).
Russian Federation. National Research Centre for Preventive Medicine, Moscow: T. Varlamova (Principal Investigator); Institute of Internal Medicine, Academy of Medical Sciences, Novosibirsk: Y. Nikitin (Principal Investigator) and V. Feigin.
Sweden. Östra Hospital Preventive Cardiology Unit, Göteborg: L. Wilhelmsen (Principal Investigator); Department of Internal Medicine, Kalix Lasarett, Kalix: F. Huhtasaari (Principal Investigator) and V. Lundberg; Department of Medicine, Umeå University Hospital: P.O. Wester (Principal Investigator), K. Asplund, and B. Stegmayr.
Yugoslavia. Novi Sad Health Centre: M. Planojevic (Principal Investigator) and D. Jacovljevic (Former Principal Investigator).
MONICA Management Center World Health Organization, Geneva, Switzerland. I. Gyarfas (Responsible Officer), Z. Pisa (Former Responsible Officer), S.R.A. Dodu (Former Responsible Officer), S. Böthig, I. Martin, M.J. Watson, and M. Hill.
MONICA Stroke Advisory Group. K. Asplund, R. Bonita, D. Eisenblätter, S. Hatano, M. Schroll, P.O. Wester, Wu Zhaosu, H. Tunstall-Pedoe, and J. Tuomilehto.
MONICA Data Center. National Public Health Institute, Helsinki, Finland: K. Kuulasmaa (Responsible Officer), J. Tuomilehto (Former Responsible Officer), V. Moltchanov, A.-M. Rajakangas, E. Ruokokoski, V. Molchanov, and J. Torppa.
MONICA Quality Control Center for Event Registration. University of Dundee, Scotland: H. Tunstall-Pedoe (Responsible Officer), K. Barret, and C. Brown.
MONICA Steering Committee. S. Sans (Chair), A. Evans (Chair, Publications Subcommittee), M. Hobbs, H. Tunstall-Pedoe (Rapporteur), I. Gyarfas, K. Kuulasmaa, and A. Shatchkute; Consultants: A. Dobson, Z. Pisa, O.D. Williams; previous Steering Committee: F. Gutzwiller, S.P. Fortmann, A. Menotti, P. Puska, S.L. Rywik, U. Keil, R. Beaglehole, and former Chiefs of CVD WHO (Geneva, Switzerland) V. Zaitsev (WHO, Copenhagen) and J. Tuomilehto; and former Consultants: M.J. Karvonen (Helsinki, Finland), R.J. Prineas (Minneapolis, Minn), M. Feinleib (Bethesda, Md), and F.H. Epstein (Zürich, Switzerland).
The authors are indebted to Dr Ruth Bonita for reviewing the manuscript.
- Received July 28, 1994.
- Revision received November 21, 1994.
- Accepted December 16, 1994.
- Copyright © 1995 by American Heart Association
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