Upsala J Med Sci 84: 235-246, 1979 A Prospective Epidemiological Survey of Cerebrovascular Disease in a Swedish Community Andreas Terent From t h e Department of Internal Medicine, University Hospital, U p p s a l a , S w e d e n ABSTRACT A prospective epidemiological study of cerebrovascular diseases and tran- sient ischemic attacks (TIA) is presented. During a three-year period the an- nual incidence of strokes was 2.90 and of TIA 0.45 per thousand population. This difference in incidence and the disparities in age characteristics favour the hypothesis that TIA precedes only a minority of the strokes. The short-term mortality is high among the stroke patients. INTRODUCTION Chronic illness, such as cardiovascular disorders and malignant neo- plasms, now dominate the panorama of diseases in middle-aged and old people in the industrialized countries (15). In Sweden, as in many other countries, cere- brovascular disease(stroke) is one of the leading causes of death ( 8 , 17). Cerebrovascular disease (0) ranks as the number-one diagnosis on the list of days spent in hospital in the Uppsala region (20). Numerous community-based ( 3 , 4, 5, 10, 11, 12, 16, 18, 23, 24, 27, 30, 35, 41) as well as hospital-based (1, 2, 7, 28, 40) studies of CVD have been pub- lished, but s o far very few have dealt with all kinds of stroke at all ages (27, 41). The aim of the present investigation was therefore to register all strokes in a well-defined area. The prognosis in CVD and factors influencing it were also studied, as well as socio-medical aspects o f the disease, and these results will be reported elsewhere. The information collected should provide a basis for the planning of care of patients with diseases of this group ( Studied area and population The municipality of Sijderhamn consists of 7, 32). a small town with rural surroun- dings. In this self-administered area, of 1,062 sq.km, the population was 32,250 in 1975 at the beginning of the study and 32,000 in 1978 at the end 235 (25). The age distribution was similar to that of the general Swedish popula- tion (Fig. 1 ) . There is only one hospital in the community. The general prac- titioners are usually eight in number and they work in close co-operation with the staffs o f the medical and surgical departments of the hospital. METHODS I n May 1975 a stroke register, for recording of all cases of stroke, both those with long-standing symptoms and those with transitory ischemic attacks (TIA), was set up at the Sijderhamn Hospital, for the purpose of the present 8 y e a r s 90-94 80-84 70-74 60-64 50- 54 40- 4L 30-34 20-24 10-14 0- 4 I 1 I I 1 1500 1000 500 500 1000 1500 No.of i n d i v i d u a l s d P A g e , y e a r s 90-94 8 0-84 7 0-74 6C-64 50-54 40-4L 30-36 20-24 10-14 0 - L I I 1 I I 3bo 200 100 100 200 300 No.of i n d i v i d u a l s . l o 0 0 Fig. 1 A. Fig. 1 B. Fig. 1 . The population by age in Sijderhamn ( 1 A ) compared with the Swedish population ( 1 B ) on 31 December, 1 9 7 4 . 236 study. Before the registration started the diagnostic criteria and the therapy t o be given were defined. Information concerning the stroke registration, including the diagnostic criteria and therapy, was given continuously to all doctors at the hospital, and to the general practitioners in the district. All nursing institutions were repeatedly asked to report definite and suspected cases of stroke. The hospital records were checked daily by the registered nurse. All death certificates for permanent residents of Sijderhamn, issued in the district during the period or obtained from the Institute of Forensic Medicine in Uppsala, were examined. One important function in the study was carried out by a special registered nurse, who was responsible for the tracing and primary registration of new cases and for calling patients for follow-up. The initial physical examination, either in hospital or elsewhere, was performed in all cases by members of the medical staff, with use of a special form. Interviews were conducted and physical examinations performed on admis- sion to hospital, after three months and then once a year. In the event of a new stroke the procedure was started from the beginning again. After exactly three years the registration was stopped but the follow-up, including the examinations mentioned above, is still continuing. The same doctor (the author) was responsible for the final registration, throughout the study period. De f in i t ions The definitions of stroke and TIA are in accordance with the recommenda- tions of WHO. Thus, stroke was defined as "rapidly developed clinical signs of focal (and/or global) disturbance of cerebral function, lasting longer than 24 hours or leading to death with no apparent cause other than vascular". The term "global" mainly applies to the cases of subarachnoid hemorrhage. TIA was defined as "rapidly developed clinical signs of focal cerebral - dysfunction of presumed vascular origin not lasting more than 2 4 hours". The term recurrent stroke was used for a new stroke taking place more than three weeks after an initial stroke. I n the case of TIA recurrence meant a new attack after a symptom-free interval of more than 2 4 hours. Comments on diagnoses The diagnosis was based mainly on clinical observations. A diagnosis of hemispheric lesion was given if one o r more of the follow- ing were observed: hemiparesis, Grasset's phenomenon, hemisensory l o s s , apha- sia, facial nerve paresis of the central type, eye deviation, homonymous anop- sia, abnormal finger-to-nose test of the non-atactic type, or unilateral posi- tive plantar reflex. 237 A brainstem lesion was indicated by cranial nerve deficits of the lower motor neuron type. Doll's eye (loss of eye movements when the head is quickly rotated) or unilateral loss of the pupillary reflex was also taken as a sign of a brainstem lesion. Cerebellar lesions are known to present with a large variety of symptoms, but a combination of typical tremor in the finger-to-nose test, dysdiadochoki- nesis and nystagmus were primarily regarded as signs of cerebellar dysfunction. A macroscopically hemorrhagic cerebrospinal fluid (CSF) indicated intracerebral breakthrough-bleeding or subarachnoid hemorrhage, depending on the presence or absence of localizing symptoms. An embolic infarction was suspected in patients with mitral valve disease with atrial fibrillation, patients with paroxysmal atrial fibrillation of other causes and in patients with infarction. Exclusions Patients who were unconscious at the onset of other recent myocardial neurological symptoms were excluded from the TIA group because of the possibility of the attack being an epileptic seizure. Migraine patients, who sometimes fit the definition of TIA, were naturally not included. Drop attacks or vertigo without any other symptoms were not sufficient for a diagnosis of TIA because of difficulties in the differential diagnosis. Treatment design The patients were treated according to the relevant principles of the medical department, which meant that no intensive care was available except for a few cases. Neither was it the rule to use vasodilators, edema-reducing agents or low-molecular weight dextran as a regular procedure. Early mobilization was prescribed, except in the case of subarachnoid hemorrhage. Anticoagulant treatment with warfarin sodium was given to patients with TIA or stroke due to embolism. The TIA patients received this treatment for two years. No time limits were set for the embolism patients. The TIA patients with unilateral symptoms who showed corresponding carotid lesions at angiography were consi- dered for surgery. Stat is t ics The incidence density (ID, in the text simply called incidence) is expres- sed as the number of new cases per 1,000 population and year. The five-yearly increase of the incidence was estimated by adjusting the formula ID = a . k to the stroke and the TIA groups, respectively. "t" stands for the number given to each consecutive five-year age group in which stroke cases were registered; the lowest age group in which stroke appeared being No. 1. Thus, when t increa- t 238 sed one unit, there was a simultaneous increase in ID by (k - 1 ) * 100 %. The chi-square test was used when testing variables within the stroke and the TIA groups, respectively. When testing for differences between these two groups the variables studied, e.g. mean age, were thought to have a normal distribution due to the large number of observations (the central limit theorem). The cri- tical value for A at the 95 % significance level was - 1.645 in one-sided tests. I I 15 10 5 A g e . years 90-9d 80-8L 70-76 - 6 0 - 6 4 50-5C 40-44 30-34 I I I 5 10 15 A g e , I 30 20 10 10 20 30 I I 1 1 I No. of p a t i e n t s Fig. 2. A Fig. 2 B. ?ig. 2. The sex and age distribution of cases of stroke (2 A) and TIA (2 B ) in jijderhamn 1975 - 1978. 239 RESULTS Between 1 May 1975 and 30 April 1978, a total of 338 strokes and 51 TIAs were registered, of which 57 strokes and 7 TIAs were recurrences (Table 1). The number of strokes and TIAs were almost identical in each year of the study. The sex and age distribution are shown in Fig. 2. The mean age in the stroke group was 71.1 + 1.7 years for men, 75.4 + 1.7 years for women for both sexes combined. Up to the age of 80 years there tely large number of men (x2 = 10.85 to be compared to - - obs and 73.1 z 1.2 years was an unproportiona- L x o.95(4) = 9.488). Table 1. Number of cases of stroke and TIA, Soderhamn, 1975-78. New stroke Recurrence New TIA Recurrence First year 92 6 14 2 Second year 95 23 16 3 Third year 94 28 14 2 28 1 57 44 7 In the TIA group the mean age for men was 67.7 z 5.2, for women 66.7 z 3.7 and for the whole group 67.2 3.6. There was no significant sex difference in this group with respect to age. On the other hand, there was a significant age difference (A 0.95 group. = -11.20) between the total stroke group and the total TIA The relative risks of stroke and TIA were found to increase exponentially with age (Fig. 3), but some differences were found between them. Firstly, there were no TIA patients below the age of 40 years, whereas there were three stro- kes in this age group (one cerebellar hemorrhage and two subarachnoid hemorr- hages). Secondly, the incidence of stroke increased by 55 % per 5-year interval compared with 36 % for TIA. The overall incidence of stroke was 2.90/1000/year and that of TIA 0.451 1000/year. After correction for differences in age and sex, the corresponding incidences in the total Swedish population are calculated to be 2.50/1000/year and 0.39/1000/year, respectively. Up to 30 April, 1978, 130 (46 % ) of the stroke patients and 3 (7 X ) of the TIA patients had died. During the same period of time 4 TIA patients developed completed stroke, including one of those who died. A history of TIA was found in 39 (14 %) of the patients with completed stroke. Lumbar puncture was performed in 60 'Z of all patients. The other diagnos- tic procedures are listed in Table 2 and the different types of stroke in Table 3. 240 Table 2 . Diagnostic procedures besides clinical examination and lumbar punc- ture. No. of patients Stroke TIA Computed tomography 3 0 Cerebral arteriography 56 10 Isotope-encephalography and EEG 22 2 Isotope-encephalography 10 4 EEG 32 4 X-ray of skull or echoencephalo- 76 4 graphy 50- 10- 5- Table 3. Types of stroke. CSF exami- Total nation Autopsy No. z Cerebral infarction 1 2 8 4 132 4 7 . 0 Intracerebral hemorrhage 4 0 9 49 1 7 . 4 Subarachnoid hemorrhage 12 3 15 5 . 3 Unclassified - - 85 3 0 . 3 281 100.00 IoLog incidence A A A h A A A 0 A 0 A 0 A A 0 A A 00 0.1 %O 40 50 60 70 80 90 n - I 1 1 I I I I Fig. 3 . The age-specific incidence of stroke (triangles) and TIA (circles) in Sijderhamn in the pe- riod 1975 - 1 9 7 8 . Age, years 241 It is expected that some, at least, of the patients in the 'unclassified' group in Table 3 will be assigned to one of the other three groups when the results of all diagnostic procedures have been analysed. This will be reported in a future communication. During the study 31 cases of suspected stroke were excluded. The most common reason was the demonstration of a cerebral tumor or an extradural hemorr- hage. Other diagnoses giving reason for exclusion were Bell's palsy, Parkinson's disease and peripheral neuropathy. Of the patients registered, 90.7 Z were examined and treated at the medi- cal department from the time of onset of symptoms. Thus, less than 10 Z of the patients were primarily treated in their own home or an old people's home, or were found dead from a stroke. Except in the last case they were all examined, mostly several times, by the same doctor who was responsible for the final registration. DISCUSSION The choice of a small and very well-defined geographical area has the advantage that it diminishes the risk of patient l o s s . A final check-up showed that during the three-year period less than 10 per cent of the patients with stroke had been treated or had been found dead before admission to hospital. This figure is well at a level with those reported by other investigators ( 4 , 16, 36). By using the WHO definitions for stroke and TIA, a comparison with other results is possible. On the other hand, there i s still a lack of simple and safe methods for diagnosing different types of strokes. I n some comparable studies (3, 35) the diagnosis of a hemorrhagic lesion was based on the same criteria as were used here, and a similar definition was also used by Kannel (22) in the Framingham study. The diagnosis of thrombotic or embolic lesions has been made without any uniformity. The only factor in common in previously presented epidemiological studies has been an exclusion diagnosis with absence of evidence of intracrsnial bleeding (9). I n the present study the lesion was considered of thrombo-embolic origin if the CSF was non-hemorrhagic or if autopsy showed cerebral infarction. However, 30 Z of the cases still remain unclassified. The TIA diagnosis is solely clinical (16). Although the great majority of the TIA population have arteriographically visible lesions in the neck vessels (31, 36, 38, 39), TIA patients lacking these have the same prognosis (39). I n spite o f exclusion of some cases with a difficult differential diagnosis, TIA as a whole i s more unreliable as a diagnostic entity than stroke, as the fin- dings may have disappeared at the clinical examination. 242 The frequency of autopsy was low in this material, owing to the traditions in this area. However, even in the case of a high autopsy rate it may be diffi- cult to draw firm conclusions from the autopsy in every case (21, 24, 27). Thus, Jorgensen and Torvik (21) found evidence of CVD in 320 patients, of whom only 196 had had previous clinical signs. Recently the combined use of computed tomography and CSF spectrophotometry has been reported to increase the diagnos- tic reliability (37). The precision of the measurement must be high to permit an extrapolation of the incidence rates from Sijderhamn to other communities (29). Although the population of Sijderhamn is rather small, this precision is certainly increased by the fact that a three-year period was used for the study. The incidence of new strokes in the present material, 2.9/1000/year, may by compared with that found previously in other countries. In Finland (4) an incidence of 1.42/1000/ year has been reported, while in Denmark (7) it has been estimated to be 2.2/1000/year for males, and 2,5/1000/year for females. These seemingly large differences between the Finnish figure, on the one hand, and the figures from the Danish and the present study, on the other, are reversed if the annual age- -specific incidences are calculated (Table 4). In this case the incidence is highest in Finland and lowest in Denmark, with the Sijderhamn figures in the intermediate position. This again illustrates the great influence of the age composition of the population on the incidence (25). The proportion of the population above 65 years in the Finnish study was 5.2 per cent, while the corresponding figures for the Danish and the present study were 21 and 18.2, respectively. In Gothenburg, one study with stroke registration in people up to 66 years of age has been published (16). The incidence of new strokes in that city was 0.52/1000/year, compared with 0.53/1000/year in the same age group in Sijderhamn. Thus, there seems to be no difference in this respect between a big city and a small town. One retrospective investigation of hospital records in Table 4. Annual incidence of stroke in some Scandinavia communities, per 1,000 population. Commun it y Study Males Females years Age (years) Age (years) 55-64 65-74 75-84 55-64 65-74 75-84 Fredriksberg 1971-73 4.5 8.6 14.9 1.9 5.1 14.2 Denmark (35) Espoo-Kauniainen 1972-73 4.9 12.2 26.8 2.5 9.5 21.5 Finland (3) Sijderhamn 1975-78 3.4 10.6 22.7 1.0 7.3 17.2 Sweden 17-792856 243 t h e Uppsala r e g i o n i n 1964 r e v e a l e d an i n c i d e n c e of 2 . 3 / 1 0 0 0 / y e a r , i n c l u d i n g some c a s e s (18 X ) n o t s a t i s f y i n g t h e s t r o k e c r i t e r i a and some w i t h T I A ( 3 3 ) . I n a n o t h e r r e t r o s p e c t i v e s t u d y of h o s p i t a l i z e d p a t i e n t s , F r i t h z (13) c a l c u l a t e d t h e i n c i d e n c e of s t r o k e below 70 y e a r s of a g e t o b e 0 . 3 6 / 1 0 0 0 / y e a r . T h i s i n c i - d e n c e i s based on f i g u r e s from 1967 t o 1971. The p r e s e n t c o r r e s p o n d i n g f i g u r e i n Sijderhamn i s 1 . 0 / 1 0 0 0 / y e a r . A d e c l i n e w a s r e p o r t e d f o r t h e two d e c a d e s up t o 1971 ( 6 , 1 4 ) , a f t e r which t h e l e v e l remained unchanged up t o 1976 ( 1 9 ) . Though t h e r e h a s been a s h i f t towards a l a r g e r p r o p o r t i o n of o l d p e o p l e between t h e two p e r i o d s 1967 - 1971 and 1975 - 1978, t h i s c a n n o t p o s s i b l y e x p l a i n t h e d i f f e r e n c e between 0.36 and 1.0. T h i s d i s c r e p a n c y p o s s i b l y r e f l e c t s t h e d i f f i - c u l t i e s of c a s e - f i n d i n g i n r e t r o s p e c t i v e s t u d i e s . The T I A i n c i d e n c e i n Sweden i s s o f a r unknown. The i n c i d e n c e i n Sijderhamn, 0 . 4 5 / 1 0 0 0 / y e a r , c a n o n l y be compared w i t h f i n d i n g s i n t h e USA ( T a b l e 5 ) . I n T a b l e 5 . Annual i n c i d e n c e o f T I A and s t r o k e i n v a r i o u s communities, p e r 1,000 p o p u l a t i o n . Community Age T I A S t r o k e y e a r s Sijderhamn A 1 1 0.45 2.90 R o c h e s t e r ( 2 7 , 41) A l l 0.31 1.54 S e a l Beach (12) - > 52 1 . 1 7 . 1 R o c h e s t e r ( 4 1 ) t h e i n c i d e n c e of T I A a t a l l a g e s w a s 0.31/1000/year. I n S e a l Beach ( 1 2 ) , w i t h a p o p u l a t i o n above t h e age of 55 y e a r s i t was 1 . 1 / 1 0 0 0 / y e ~ r , compared w i t h 1 . 0 / 1 0 0 0 / y e a r i n t h e same a g e c l a s s e s i n Sijderhamn. Thus, s t r o k e seems t o be a b o u t s i x t i m e s more f r e q u e n t t h a n T I A . Our f i n d i n g s , as w e l l a s r e p o r t s of o t h e r a u t h o r s ( T a b l e 6 ) , show t h a t a h i s t o r y of T I A i s known i n o n l y 15 - 20 p e r c e n t of t h e s t r o k e p a t i e n t s ( 3 , 1 6 ) . There i s one e x c e p t i o n , namely t h e s t u d y from R o c h e s t e r ( 2 7 ) . Here 73 p a t i e n t s o u t of 7 7 7 w i t h presumed c e r e - b r a l i n f a r c t i o n had e x p e r i e n c e d T I A , c o n s t i t u t i n g o n l y 5.9 p e r c e n t of t h e T a b l e 6 . H i s t o r y of T I A i n s t r o k e p a t i e n t s i n v a r i o u s s t u d i e s . No. of Age No. w i t h P e r c e n t a g e Community p a t i e n t s y e a r s T I A w i t h T I A Sijderhamn 2 8 1 A 1 1 39 13.9 Espoo-Kauniainen ( 9 ) 286 A 1 1 44 15.4 Harlem (23) 328 A 1 1 41 12.5 R o c h e s t e r ( 3 , 41) 1245 A l l 73 5.4 244 total number of 1,245 stroke patients. This latter low figure supposedly ref- lects the difficulties in identifying this diagnosis retrospectively. In Saderhamn the youngest cases with stroke come at a lower age than those with TIA. In contrast, however, the mean age is lnwer in the TIA group. A l s o , the incidence of TIA increases more slowly than that of stroke. 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