Background and Purpose Stroke incidence has increased in some countries and decreased in others. After 20 years of intensive antihypertensive treatment the latter could be expected, and we have evaluated the sex-specific temporal trends in stroke incidence using 17 years of follow-up in the Copenhagen City Heart Study.
Subjects and Methods Our cohort comprised 19 698 subjects living in Copenhagen, Denmark. They were invited for health examinations in the following time periods: 1976 through 1978, 1981 through 1983, and 1992 through 1994. Trends are presented for all persons who attended at least one of the two first examinations as well as the total cohort including nonresponders. Subjects between 45 and 84 years of age were followed from March 1, 1976 until March 1, 1993. Changes in age-specific stroke incidence were calculated by means of Poisson regression analysis.
Results For subjects aged 45 to 64 years, no significant trends were observed, with an annual incidence rate ratio of 1.00 (95% confidence interval [CI], 0.97 to 1.03) and 1.04 (95% CI, 0.99 to 1.08) for men and women, respectively. In subjects aged 65 to 84 years a significant decrease in stroke incidence was found in men, whose annual rate ratio was 0.97 (95% CI, 0.95 to 0.99), but not in women, whose annual rate ratio was 0.98 (95% CI, 0.95 to 1.00). Throughout four observed periods the stroke incidence among men remained significantly higher than that for women.
Conclusions During the period from 1976 to 1993 there has been a decline in incidence of stroke in men and women aged 65 to 84 years that was significant only in men, whereas no changes were found for persons aged 45 to 64 years.
Previous reports on the incidence of stroke among men and women from the Copenhagen City Heart Study found that the incidence rate did not change significantly between 1976 and 1988 either in men or in women.1 2 Several factors may have influenced stroke incidence during the last couple of decades. The antihypertensive treatment, which became a well-established therapy in Denmark as in most Western countries in the early 1970s, may have caused a reduction in incidence. Furthermore, public awareness of lifestyle factors and physiological factors predisposing to cardiovascular diseases may have led to a lower incidence of stroke. We are now able to evaluate 17 years of follow-up of the study population to investigate trends in incidence for the period 1976 through 1993.
Subjects and Methods
The Copenhagen City Heart Study is a prospective population study comprising a cohort of 19 698 subjects who have been followed since 1976. The persons were selected from a defined district in Copenhagen (two thirds from Østerbro and one third from Nørrebro). Less than 2% of the population was of non-Caucasian origin, and socioeconomically the majority was middle class. The selection of participants was random within age- and sex-strata, with a greater sample proportion of the study population being persons between 40 and 60 years of age at the first examination. This was done to ensure that the study could provide sufficient information about risk factors for and end points of cardiovascular disease. Everybody has had the same opportunity to consult their general practitioner and to obtain medical treatment in highly specialized hospitals, since such services are free of charge in Denmark. All subjects were invited to three examinations held from 1976 through 1978, from 1981 through 1983, and from 1992 through 1994. A total of 15 499 persons attended at least one of the two initial examinations and are hereafter referred to as responders; the remaining 3828 are referred to as nonresponders. Before the first examination 371 persons died, and 178 had had a stroke before the study started, and they were excluded from the analyses. The follow-up period for persons who participated only in the second examination was restricted to the time after participation.
To enable exclusion of subjects with stroke before the onset of the study period, participants were asked at the examinations if they had ever suffered from a cerebrovascular event, regardless of whether they were hospitalized or treated at home. If they answered positively, they underwent a neurological examination by neurologists. In cases in which doubt remained about the diagnosis, additional information was acquired from the general practitioner, family, or nursing home. For nonresponders, the exclusion of persons with cerebrovascular events before the onset of the observation period is restricted to hospitalized cases. The procedures and the complete questionnaire used at the examinations have been described previously.3
For all participants, responders as well as nonresponders, information about death and cerebrovascular disease was obtained from the National Health Service Register of Causes of Death and the Danish National Hospital Discharge Register, which contains all discharge diagnoses from all hospital admissions. The search criteria were defined as World Health Organization’s International Classification of Disease, Eighth Revision (ICD 8), diagnosis codes 430 through 438. Discharge letters or patient files were retrieved to validate whether the person had suffered from stroke. In cases where this material did not provide sufficient information, for example in the description of neurological deficits to support the diagnosis of stroke, all hospital records and additional information from the patient’s general practitioner, family, or nursing home were collected.
As described, the case ascertainment is more complete for responders, because information about nonhospitalized events is available. Hence, the results for all the data from the registries as well as for the responders alone are both presented. By this means, information is obtained about how persons who participate in a cohort study may differ from the background population with regard to stroke incidence.
Stroke cases that had led to death without prior hospitalization were found in the National Health Service Register of Causes of Death. Only cases with cerebrovascular disease listed as the first or second cause of death were included in our analysis as stroke.
In this report only first-time strokes are included. The World Health Organization’s definition of stroke was used to determine whether the person’s symptoms were likely to be caused by stroke. Stroke is defined as an acute disturbance of focal or global cerebral function with symptoms lasting more than 24 hours or leading to death of presumed vascular origin (ie, sudden onset of unconsciousness with no known prior disease that can explain the condition; where the blood pressure remains stable or increased; and where there is no evidence of metabolic disturbances or poisoning). The definition enables distinction between stroke and transient ischemic attack.4 Persons with a history of transient ischemic attack before the observation period were not excluded. The cases were divided into hemispheric stroke, ischemic infarction in the hemispheres, intracerebral hemorrhages, subarachnoid hemorrhages, stroke in the brainstem, or unspecified stroke. Subarachnoid hemorrhages were identified and evaluated like the other stroke types but were not included in the analysis, and persons with diagnosed subarachnoid hemorrhages were censored from the day of the diagnosis. To distinguish between ischemic infarction, intracerebral hemorrhage, and subarachnoidal hemorrhage either CT or MR scan, autopsy, spinal fluid examination, or operation description was necessary. If infarction could not be visualized by CT scanning but the person had symptoms consistent with stroke, a diagnosis of ischemic infarction was made.5 The diagnosis of stroke was not applied in cases where a scan had revealed signs of prior cerebrovascular disease but without history of any symptoms.
Poisson regression was used to analyze changes in incidence rates between the four periods (the start and ending of study periods being the March 1 and February 28/29) 1976 through 1980, 1980 through 1984, 1984 through 1988, and 1988 through 1993.6 This method enables a thorough control for differences in age in the periods being compared; adjustment for the confounding effect of age was done by dividing into 2-year age groups. Furthermore, the method makes it possible to estimate the trend between the study periods as the annual incidence rate ratio, assuming the incidence rate is stable for the years constituting one period. In all the analyses we tested at the 5% level by using the likelihood ratio test if a nonlinear description of the trends would be more accurate. The calculations were carried out using the statistical software package STATA.7
From March 1, 1976 to February 28, 1993, 1101 stroke cases were identified among subjects aged 45 to 84 years, of which 882 occurred among responders. Because of the limited number of cases and person-years in the outer age bands, we chose to report the time trend for only subjects aged 45 to 84 years. The crude age- and sex-specific rates for those aged 45 to 84 years are shown in Table 1⇓. The mean age of this age group at the beginning of the study period was 51.6 years for male responders and 51.4 years for nonresponders, while for female responders it was 51.6 years and for nonresponders 53.9 years.
The stroke types were classified as follows: 34.3% nonspecified hemispheric strokes, 38.7% hemispheric infarctions, 7.0% intracerebral hemorrhages, 4.1% brainstem strokes, and 15.9% nonspecified strokes.
In men 627 cases were observed (56.9%), while in women 474 cases were observed (43.1%).
The trends of stroke incidence are illustrated in the Figure⇓. In men and women aged 45 to 64 years, no significant trends were observed, with annual rate ratios of 0.99 (95% confidence interval [CI], 0.97 to 1.03) and 1.04 (95% CI, 0.99 to 1.08), respectively. In subjects aged 65 to 84 a significant decline in stroke incidence was found in men but not in women, with annual rate ratios of 0.97 (95% CI, 0.95 to 0.99) and 0.98 (95% CI, 0.95 to 1.00), respectively. In all four periods (1976 through 1980, 1980 through 1984, 1984 through 1988, and 1988 through 1993), the incidence rates were significantly higher for men than for women as shown in Table 2⇓.
The trends of stroke incidence among responders showed the same pattern as in analyses of all the data from the registries: for men aged 45 to 64 years the annual rate ratio was 1.00 (95% CI, 0.97 to 1.04), for women aged 45 to 64 years the annual rate ratio was 1.04 (95% CI, 0.99 to 1.09), for men aged 65 to 84 years the annual rate ratio was 0.97 (95% CI, 0.94 to 0.99), for women aged 65 to 84 years the annual rate ratio was 1.00 (95% CI, 0.97 to 1.03). Among responders men had a significantly higher incidence rate than women, also shown in Table 2⇑.
In women, nonresponders had a higher annual rate of stroke than responders, relative risk 1.58 (95% CI, 1.26 to 1.97); whereas in men, there was no statistically significant difference between nonresponders and responders, relative risk 0.99 (95% CI, 0.80 to 1.21).
The annual changes in incidence of stroke between men and women are also shown in Table 2⇑, and the rate ratio between male and female responders aged 65 to 84 years decreased significantly. Neither in the analyses of all participants aged 65 to 84 years nor in subjects aged 45 to 64 (all participants as well as responders) did we find significant changes in rate ratio between men and women.
In all groups we tested at the 5% level using the likelihood ratio test if a nonlinear description of the trends would be more accurate, but this approach did not give a significantly better description of any of the changes in rates.
This study shows that stroke incidence remained stable from 1976 through 1993 in Copenhagen among men aged 45 to 64 years and women aged 45 to 84 years, whereas a significant decrease was found in men aged 65 to 84 years.
The Copenhagen City Heart Study does not involve general practitioners, thus detection of nonhospitalized cases depends upon the information given by the responders at the examinations. This may lead to an underestimation of the occurrence of stroke in the study population, and therefore there may be a tendency to underestimate the true incidence. On the other hand, the ascertainment of fatal cases and hospital admissions can be assumed to be complete, and the uniform procedures that have been used throughout the years enable analysis of temporal trends.
Reported trends of stroke incidence from different parts of the world show different tendencies, as shown in Table 3⇓. In Rochester, Minnesota, the postwar period decrease has been replaced by a slight increase since the beginning of the 1980s, and increment of stroke incidence was also reported from the former East Germany from the 1970s through the 1980s.8 9 10 In Auckland, New Zealand, no overall change in stroke incidence was found comparing the years 1981 and 1991, although the rate rose among women younger than 75 years and fell in men of 75 years or older.11 In two Japanese regions, a decline was reported for the two periods 1961 to 1976 and 1965 to 1983.12 13 The Honolulu Heart Program reported a decline in men aged 45 to 68 years observed in the period 1969 to 1988.14 From Novosibirsk, Russia, a region with high incidence rates, a decline was reported over the years 1982 to 1992, and in Finland a decline in stroke incidence was also evident between 1983 and 1992.15 16 Furthermore, sex-specific changes have been reported. In a study from Söderhamn, Sweden, the male incidence was four times higher than that for females from 1975 to 1978; but in the period 1983 to 1986 the incidence was almost equal because of a marked increment in stroke incidence in women.17 The Swedish report, however, is not representative of changes in Sweden because a study from Göteborg found no significant changes in stroke incidence rates for men and women aged 15 to 65 years.18 In a study from China the reported decline in stroke incidence occurred almost exclusively in males.19
In previous analyses of stroke incidence in the Copenhagen City Heart Study, from the period 1976 to 1988, no significant decrease was observed among responders, but analyses pooling responders and nonresponders were not performed.2 In the present study we did those analyses and we found no significant decline in the period 1976 to 1988 in the pooled data either in men or women (results not shown).
In another suburb of Copenhagen, known as “Frederiksberg,” an increase in stroke incidence was reported for men aged 65 to 84 years, when comparing the two periods 1972 to 1974 and 1989 to 1990.20 The rates for men and women aged 65 to 84 years in the period 1989 to 1990 and our corresponding rates in the period 1988 to 1993 are very similar (results from the Frederiksberg study: The incidence rates per 1000 years were 11.90 and 15.72 in men aged 65 to 74 and 75 to 84 years, respectively; whereas for women the incidence rates per 1000 years were 3.96 and 11.98 in subjects aged 65 to 74 and 75 to 84 years, respectively). The incidence rates for the period 1972 to 1974 were lower in the Frederiksberg study than in the Copenhagen City Heart Study, however, and we have no explanation for this difference.
Like most Western countries, widespread use of antihypertensive treatment was well established in Denmark in the beginning of the 1970s, and a significant reduction in the incidence of stroke could be expected. In a study of antihypertensive treatment and stroke incidence, there were no changes in men until 10 years after improvement in the control of blood pressure.21 It is possible that the effect in men in this study could be a delayed result of primary prevention. For subjects aged 45 to 64 years no significant changes were observed in either sex, which may reflect that younger people with hypertension have been treated from onset of the disease, and thereby avoided a long period of high blood pressure, in contrast to older people.
The changes in stroke incidence among subjects aged 65 to 84 years are not identical in men and women. While the decrease in stroke incidence can be found in men both in analyses performed on the total male cohort as well as on only responders, in women the decrease is not significant in either analysis. Between the two examinations in the two periods 1976 to 1978 and 1981 to 1983, the proportion of men aged 75 to 79 and more than 80 years old who received antihypertensive treatment increased relatively, by 57% (11.5% to 18.0%) and 134% (6.8% to 15.9%), respectively; whereas in women at the same ages the increases were 24% (20.5% to 25.5%) and 32% (27.3% to 36.1%), respectively.3 Thus, a change in the treatment of hypertension is not likely to be the sole explanation for the observed changes.
Smoking habits may also have had an impact on the incidence of stroke. In recent years the proportion of Danish men aged 65 years or older who smoke has been stable or decreased, whereas the proportion of Danish women aged 65 years or older who smoke has increased.22 The effect of smoking and cessation of smoking on risk of stroke has been investigated in different studies.23 24 25 26 In the present article we have not assessed the effect of changes in smoking habits, but it has previously been shown that between 50% and 60% of both males and females in the study population were current smokers.27
In our data there is a significantly higher incidence of stroke among female nonresponders as compared with female responders, whereas the difference is not significant in men. Furthermore, whereas the mean ages for male responders and nonresponders are very similar, the mean age for female nonresponders is more than 2 years higher than that for responders. That may reflect a sex-specific selection in cohort studies, ie, men and women have different reasons for not participating.
In conclusion, 17 years’ follow-up of stroke incidence among the participants in the Copenhagen City Heart Study showed a decline in subjects aged 65 to 84 years significant only in men, whereas for men and women aged 45 to 64 years no significant changes occurred.
This study was supported by funds from the Danish Heart Foundation, the Health Insurance Fund, King Christian the 10th Foundation, the Danish National Board of Health, and the Danish Research Council. We are grateful to G. Jensen, J. Nyboe, and M. Appleyard who initiated and conducted the Copenhagen City Heart Study.
- Received February 19, 1997.
- Revision received June 23, 1997.
- Accepted June 24, 1997.
- Copyright © 1997 by American Heart Association
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