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(Stroke. 1999;30:2529.)
© 1999 American Heart Association, Inc.
Original Contributions |
Stable Stroke Occurrence Despite Incidence Reduction in an Aging Population
Stroke Trends in the Danish Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Population
From Glostrup Population Studies, Centre of Preventive Medicine, Glostrup University Hospital, Glostrup, Denmark (P.T., M.S.), and the Danish Institute for Clinical Epidemiology, Copenhagen, Denmark (M.D., H.B.-H.).
Correspondence to Dr Per Thorvaldsen, Department of Neurology, Gentofte University Hospital, DK-2900 Hellerup, Denmark. E-mail brain{at}dadlnet.dk
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Abstract |
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Background and Purpose—A stroke register was established at the Glostrup Population Studies in 1982 with the objective to monitor stroke occurrence in the population continuously during a 10-year period and contribute data to the WHO Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project. The purpose of the current analysis was to estimate temporal trends in stroke occurrence.
Methods—All stroke events in the study population were
ascertained and validated according to standardized criteria outlined
by the WHO MONICA Project. The study population comprised all
subjects 
25 years of age. Stroke was defined by the clinical
presentation. A total of 5262 stroke events in >2 million
person-years were analyzed. Age-adjusted rates for first-ever
stroke and for all stroke events were calculated and temporal trends
estimated by means of Poisson regression.
Results—The overall annual stroke attack rate per 100 000
person-years in the age range 25 years was 272 in men and 226 in
women. Age-adjusted stroke attack rates decreased among men by 3.9%
per year and by 4.1% among women. Age-adjusted stroke incidence rates
declined by 2.9% in men and by 3.1% in women. The trends were
statistically significant in both sexes. However, the proportion of
elderly people in the study population increased during the time period
of the study. Hence the numbers of stroke victims in the population
remained largely unaltered.
Conclusions—Decreasing age-adjusted stroke incidence rates point to a reduction of stroke risk during the time period of the study. Cardiovascular prevention, in particular improved hypertension control, is believed to have contributed to the incidence reduction. However, the burden of stroke on the healthcare system did not substantially diminish. The gain likely achieved from reduction of preventable risk factors was almost counterbalanced by population aging.
Key Words: aging • cerebrovascular disorders • epidemiology • incidence
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Stroke has been studied with increasing interest and effort over the past decades, reflecting the importance of cerebrovascular diseases as a major public health issue. Stroke is the most frequent cause of disability and the third leading cause of death in the industrialized world.
On the basis of population-based stroke mortality data, it was first shown in the United States1 2 that stroke mortality rates had declined for several decades. For the years 1970 to 1985 a decline of stroke mortality rate was observed in 25 countries,3 4 most substantially in Japan, North America, and Western Europe. In most industrialized countries a parallel decline occurred in coronary heart disease mortality rates.5 6 In contrast to the decline in the Western industrialized world, stroke mortality rates increased in Eastern European countries.
Changes have been observed not only in stroke mortality rates but also in stroke morbidity. The trends obtained from national vital statistics on cerebrovascular death have been rather clear. The data on stroke incidence drawn from population-based stroke registers were for a long period of time less clear with respect to temporal trends. A decline in stroke incidence was reported from the United States,7 8 9 Asia,10 11 12 and Europe,13 14 15 but some studies have pointed to a subsequent leveling off of the decline of stroke incidence16 17 and mortality rates.18 In some of the populations studied there were no significant changes,19 20 21 22 23 24 25 or increasing rates were found in women,26 in men,27 or in both sexes.28 29 30 31 Preliminary results from the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) Stroke Project32 have shown a general tendency toward declining stroke incidence rates in most of the populations studied.
The purpose of the current analyses was to describe temporal trends in stroke occurrence in the Danish MONICA Population.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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A stroke register was established at the Glostrup Population Studies in 1982 with the objectives to monitor stroke events in the community for a 10-year period and to contribute data to the WHO MONICA Project. When collecting data for the MONICA Project we additionally registered stroke events among those older than the upper age limit for the MONICA Project. This is considered of particular importance because the vast majority of strokes occur in the elderly. The methods for case ascertainment and validation developed by the MONICA Project33 34 35 were applied. Core data for events in the age range 25 to 74 years were reported to the MONICA Data Center, and some of the data have previously been used in collaborative analyses of stroke occurrence in the subpopulation 35 to 64 years of age.32 36 37 38
Study Population
The study population was defined as all residents (
330 000)
of 11 municipalities in Copenhagen County. Stroke events were
registered for the subpopulation 25 years of age (210 000). The
population was dynamic in the sense that subjects entered the
population by reaching age 25 years or by moving into the area.
Likewise, subjects left the population when they moved out of the area
or died.
There was a shift toward higher age in the study population during 1982
through 1991. The proportion of individuals 65 years of age increased
from 10% to 14% among men and from 14% to 18% among women. The mean
age increased by 2.2 years in men and by 2.9 years in women.
Case Ascertainment
The study was community based, and all events in the population
were registered and validated irrespective of survival status and place
of occurrence and management. The major source of fatal events was
death certificates. All deaths with a stroke diagnosis in the death
certificate or that otherwise could have been caused by stroke were
registered and the cause validated. Hospitalized cases were identified
from hospital discharge diagnoses. All suspected stroke cases were
retrieved and validated. Events were validated on the basis of medical
records for 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.
Twelve percent of the events were managed at home or in institutions other than hospitals. Two thirds of these events were fatal. Only six percent of all nonfatal stroke events were managed outside hospitals. The high frequency of cases registered as managed in the hospital is partly due to the organization of health services and partly to coding practice because cases referred to the hospital for specialist evaluation on an outpatient basis within 28 days of the onset have been registered as hospitalized events. The hospitalization frequency is also in agreement with the medical tradition in Denmark and made possible by the infrastructure of the survey area, having 3 university hospitals providing practically all neurological specialist services and all neuroimaging.
Definition of Stroke
Stroke was defined as rapidly developing signs of focal (or
global) disturbance of cerebral function lasting >24 hours
(unless interrupted by surgery or death), with no apparent nonvascular
cause; it included patients with clinical signs and symptoms suggestive
of subarachnoid hemorrhage,
intracerebral hemorrhage, or cerebral
infarction. Hence the study is based on clinical diagnoses, which have
been shown to be reliable.39 In this article we report
cases with ICD codes 430 to 34 or 436 (8th Revised Version of the
International Classification of Diseases).
Stroke events have been subdivided into first or recurrent and into fatal or nonfatal. A period of 28 days was used to define case fatality and to distinguish one event from another.
Transient ischemic attacks and silent brain infarction (cases without clinical symptoms or signs) were not included. Neither were events associated with trauma, blood disease, or malignancy.
Diagnostic Procedures and Stroke Subtypes
The proportion of events investigated by computed
tomographic (CT) scan increased from 25% during the first 3 years to
46% during the last 3 years of the study period. The proportion of
fatal events in which necropsy was done fell from 49% in the beginning
to 33% by the end of the period as a result of legislative changes.
The net result of changes in diagnostic procedures was a
gradual increase in the numbers of events with sufficient
diagnostic information for stroke subtype classification
from 28% to 50%. Overall, the stroke subtype was determined in 36%
of the events. This proportion is too small for valid analyses
of temporal trends in relation to particular types of stroke.
Statistical Methods
Stroke attack rate refers to all strokes, both first and
recurrent events, whereas stroke incidence refers to first events only.
Case fatality is defined as the proportion of events fatal within 28
days of onset.
Attack and incidence rates were calculated per 100 000 person-years on the basis of 5-year age groups for subjects >24 years of age. Stroke mortality rates were calculated on the basis of fatal events. The age-adjusted rates were calculated by the direct method by use of the Danish 1990 population as reference. Trends in annual rates were evaluated by means of Poisson regression.40 Age-adjusted case-fatality rates were calculated with the use of the age distribution of the registered stroke cases as reference.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The total number of person-years studied exceeded 2 million. During the study period from 1982 through 1991, a total of 5262 events were registered and classified as stroke after the standardized validation procedure. Table 1
shows the annual population size for men and women and the numbers of
registered stroke events.
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The overall proportion of recurrent events was 21% among men and 19% among women. Six percent of those who survived 28 days after a first-ever stroke during the first 9 years of the study period had a second (recurrent) stroke within 1 year after the first stroke.
The mean age at first stroke onset was 65 years (SD 12.8) in men and 71 years (SD 14.4) in women. The aging of the study population was reflected in the mean age of patients with stroke increasing by 3 years among men and by 2.2 years among women from 1982 to 1991.
The overall annual stroke attack rates per 100 000 study
population (age 25 years) were 272 in men and 226 in women. The
corresponding rates for first-ever stoke were 217 in men and 184 in
women. Table 2 shows age-specific stroke
incidence rates for 10-year age groups. Stroke was twice as frequent in
men between 45 and 64 years of age as in women of the same age. There
was no such clear difference in the younger part of the population, and
among the oldest individuals stroke incidence was somewhat higher in
women than in men.
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Figure 1 shows temporal trends in
age-adjusted stroke attack rates; Figure 2 shows the trends in first-ever stroke.
The annual changes in age-adjusted stroke attack, incidence, and
mortality rates in different age groups are shown in Table 3. Overall, age-adjusted stroke incidence
and attack rates declined significantly in both sexes without
significant differences between age groups. Crude stroke attack rates
declined by 1.5% per year in men (P=0.02) and by 1.0% in
women (P=0.1). Crude stroke incidence rates fell less than
one-half percent per year (NS) in both sexes. Hence there were only
slight changes in the actual numbers of stroke events in the study
population.
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Figure 3 shows estimates of
temporal trends in stroke attacks in men and women together for 3
different scenarios. The upper line shows the increase in stroke
attacks that was expected in the absence of stroke risk reduction,
given the actual aging of the population during 1982 through 1991. The
middle line shows the trend in observed numbers of stroke events in the
study population, that is, the combined effect of aging and declining
stroke rates. The lower line shows the yearly expected numbers of
strokes when controlling for the effect of aging, that is, the expected
numbers of strokes if the population had not grown older.
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Overall, 1558 (30%) events were fatal within 28 days of onset. The overall case-fatality rate was significantly higher after recurrent events (35%) than after first stroke (28%) (P<0.05). Case-fatality rate increased significantly with increasing age in both men and women. Female stroke victims were older than male stroke victims, and their 28-day survival rate was poorer (34% vs 26%) but age-adjusted case-fatality rates were higher among women (32%) than among men (28%). The proportions of fatal events among all stroke events by calendar year varied between 20% and 35% in men and between 27% and 42% in women. In contrast to stroke incidence, age-adjusted annual case-fatality rates increased by 2.7% per year in men (P=0.08) and by 0.8% in women (P=0.54).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Stroke incidence rates showed a clear decrease by
3% per year
in the Danish MONICA population during 1982 through 1991. The results
are in agreement with several studies showing declining
cardiovascular and cerebrovascular disease morbidity
and mortality rates in many Western countries. The MONICA study of
coronary heart disease in the same study
population41 has similarly shown a clear fall in the
incidence of myocardial infarction. Also, stroke mortality rates
decreased. The changes were statistically significant in women but not
in men. The numbers of fatal events were smaller and the statistical
power correspondingly lower as compared with all events. The changes in
age-adjusted mortality rates follow the trend in attack rates and
reflect the changes in stroke occurrence. Decreasing mortality rates do
not per se indicate any change in the course of disease. The current
study does not comprise clinical data on stroke severity. The
case-fatality rates do not indicate any favorable change in stroke
severity as far as survival is concerned. The results indicate that
changes in population health factors have reduced the risk of
cardiovascular diseases but do not point to any
significant alleviation of the burden of stroke, neither on society nor
on the individual once a stroke victim. A reduced risk of stroke is inferred from the decline found in age-adjusted rates for all strokes and for first-ever stroke. Declining stroke rates have been attributed in part to improved hypertension control. The attributable risk for stroke from clinical hypertension is more than one third42 and the attributable risk associated with isolated systolic hypertension has been estimated to be 30%.43 Data from a series of cohorts drawn from the same background population as the Danish MONICA study population and investigated since the 1970s indicate that the prevalence of hypertension as well as population mean systolic and diastolic blood pressure fell markedly before and in the beginning of the time period of the current study.44 On this background we find it justified, viewing the decline of stroke as a likely result of primary prevention of cardiovascular diseases, in particular improved hypertension control. The current data do not permit conclusions on the effect of secondary prevention in stroke victims. About one fifth of the events were recurrent events, and this proportion did not change significantly during the years of the study.
The decrease in stroke incidence was more pronounced in women older than 54 years, among whom 84% of the events occurred, but among those younger the smaller number of events has inevitably reduced the statistical power. In populations with increasing stroke rates, such trends have been attributed to deteriorating lifestyle factors.28 The prevalence of smoking has gone down in Denmark among men since the 1960s but it increased among women, and the prevalence of heavy smokers was higher among younger than older women.45 It is possible that a generally less favorable development in lifestyle factors among younger women has limited the impact of stroke prevention in this subpopulation.
Stroke incidence rates declined steeper among men in the youngest age group than among those older. Previous studies of stroke incidence in Denmark have not been consistent with respect to stroke incidence trends in men. In 1 study, stroke incidence increased between 1972 and 1990 in men 65 to 84 years of age,27 whereas in another there was a significant decrease in men of the same age.46 Data from the Northern Sweden MONICA Stroke Register19 showed an annual decline of stroke rates of the same magnitude as in the current study in men younger than 65 years but increasing stroke incidence in those older.
A main topic in cardiovascular disease prevention
has been hypertension control, but the risk associated with
hypertension is reportedly not the same in all age groups. In men 45 to
54 years of age the percentage of strokes attributable to hypertension
was 50%, whereas it was 18% in those 65 years of
age.47 Consequently, the impact of prevention may be less
pronounced in men above middle age, who have a high risk of stroke. If
improved hypertension control was the major cause of the stroke
incidence decline in our study population it could be expected that the
preventive effect would diminish with increasing age.
The study was population based, and it was considered to be complete because of unlimited access to medical records and diagnosis registries in all sectors of the Danish healthcare system. Procedures for data collection and event validation were kept constant throughout the study period, which is a prerequisite for trend analyses. Internal validation of case ascertainment has shown that 96% of all strokes could be reliably identified from central registers of diagnosis and causes of death because of the unique central person number system. Other and theoretically less reliable sources used to identify nonhospitalized, nonfatal events contributed <5% of the material. No apparent systematic variation in this smaller proportion of events was found, and the possibility of bias from this source is considered negligible. Stroke was defined by the clinical presentation, and this definition was applied throughout the study period. Therefore, case ascertainment in principle should not be affected by the increasing use of computed tomography. This unfortunately does not guarantee that the results were unconfounded by the introduction of new diagnostic procedures. The decline in stroke rates could be slightly underestimated because neuroimaging improved case finding. On the other hand, this could be balanced by improved specificity of the early diagnosis.
The present indication of reduced stroke risk in the population is encouraging for continuing cardiovascular prevention. However, the total benefit of preventive efforts was not immediately apparent from the actual occurrence of stroke in the population studied. The as-yet nonmodifiable risk associated with age almost counterbalanced the effect of improved prevention. Individuals who had strokes were not significantly reduced in number, as predicted from the regression model using age-adjusted rates because of the shift toward higher age in the population. Consequently, the healthcare services experienced no substantial alleviation of the burden of stroke on the system. On the other hand, the number of stroke events did not increase to the extent that it would have, had there not been a significant reduction in the overall stroke risk. In many industrialized countries the populations are aging, and the situation may be similar to what we have found in the Danish MONICA Population. Hence we find it pertinent to stress that preventive measures should be considered successful even if they merely prevent things from getting worse.
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Acknowledgments |
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The DAN-MONICA Stroke Project was supported in part by grants from the Danish Heart Foundation. The authors wish to acknowledge the work done by all members of the Danish MONICA team and the support received from collaborating institutions and organizations.
Received July 12, 1999; revision received September 20, 1999; accepted September 20, 1999.
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 J. F. Meschia, T. G. Brott, R. D. Brown Jr, B. M. Kissela, J. A. Hardy, W. M. Brown, S. S. Rich, and for the Siblings With Ischemic Stroke Study Invest Correlation of proband and sibling stroke latency: The SWISS Study Neurology, March 22, 2005; 64(6): 1061 - 1063. [Abstract] [Full Text] [PDF]
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J. Sivenius, J. Tuomilehto, P. Immonen-Raiha, M. Kaarisalo, C. Sarti, J. Torppa, K. Kuulasmaa, M. Mahonen, A. Lehtonen, and V. Salomaa Continuous 15-Year Decrease in Incidence and Mortality of Stroke in Finland: The FINSTROKE Study Stroke, February 1, 2004; 35(2): 420 - 425. [Abstract] [Full Text] [PDF]
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C. Sarti, B. Stegmayr, H. Tolonen, M. Mahonen, J. Tuomilehto, and K. Asplund Are Changes in Mortality From Stroke Caused by Changes in Stroke Event Rates or Case Fatality?: Results From the WHO MONICA Project Stroke, August 1, 2003; 34(8): 1833 - 1840. [Abstract] [Full Text] [PDF]
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R. Fogelholm Editorial Comment--Explanations for International Trends in Stroke Mortality Stroke, August 1, 2003; 34(8): 1840 - 1841. [Full Text] [PDF]
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A. Terent Trends in Stroke Incidence and 10-Year Survival in Soderhamn, Sweden, 1975-2001 Stroke, June 1, 2003; 34(6): 1353 - 1358. [Abstract] [Full Text] [PDF]
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 T. H. Rainer, L. K.S. Wong, W. Lam, E. Yuen, N. Y.L. Lam, C. Metreweli, and Y.M. D. Lo Prognostic Use of Circulating Plasma Nucleic Acid Concentrations in Patients with Acute Stroke Clin. Chem., April 1, 2003; 49(4): 562 - 569. [Abstract] [Full Text] [PDF]
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T. Truelsen, N. Nielsen, G. Boysen, and M. Gronbaek Self-Reported Stress and Risk of Stroke: The Copenhagen City Heart Study Stroke, April 1, 2003; 34(4): 856 - 862. [Abstract] [Full Text] [PDF]
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H. Pessah-Rasmussen, G. Engstrom, I. Jerntorp, and L. Janzon Increasing Stroke Incidence and Decreasing Case Fatality, 1989-1998: A Study From the Stroke Register in Malmo, Sweden Stroke, April 1, 2003; 34(4): 913 - 918. [Abstract] [Full Text] [PDF]
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 M Hollander, P J Koudstaal, M L Bots, D E Grobbee, A Hofman, and M M B Breteler Incidence, risk, and case fatality of first ever stroke in the elderly population. The Rotterdam Study J. Neurol. Neurosurg. Psychiatry, March 1, 2003; 74(3): 317 - 321. [Abstract] [Full Text] [PDF]
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S. E. Vermeer, T. den Heijer, P. J. Koudstaal, M. Oudkerk, A. Hofman, and M. M.B. Breteler Incidence and Risk Factors of Silent Brain Infarcts in the Population-Based Rotterdam Scan Study Stroke, February 1, 2003; 34(2): 392 - 396. [Abstract] [Full Text] [PDF]
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S. Bak, S. H. Sindrup, T. Alslev, O. Kristensen, K. Christensen, and D. Gaist Cessation of Smoking After First-Ever Stroke: A Follow-Up Study Stroke, September 1, 2002; 33(9): 2263 - 2269. [Abstract] [Full Text] [PDF]
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H. Bronnum-Hansen, M. Davidsen, and P. Thorvaldsen Long-Term Survival and Causes of Death After Stroke Stroke, September 1, 2001; 32(9): 2131 - 2136. [Abstract] [Full Text] [PDF]
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C. Fieschi and A. Falcou Keynote address Neurology, September 1, 2001; 57(90002): S82 - 86. [Abstract] [Full Text]
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