(Stroke. 1995;26:1787-1793.)
© 1995 American Heart Association, Inc.
Articles |
From the Section of Neuroepidemiology, Neurological Clinic, University of Ferrara (G.L., I.C.); the Division of Neurology, General Hospital of Belluno (M.G., G.F.) and Feltre (G.C.); the Division of Medicine and Geriatrics, General Hospital of Belluno (G.A., R.C., M.M.); and the Division of Medicine, General Hospital of Agordo (P.O.), Auronzo (F.A., C.B.), Lamon (A.C.), and Pieve di Cadore (D.M.) (Italy).
Correspondence to Giuseppe Lauria, MD, Clinica Neurologica, Università di Ferrara, via Della Giovecca, 203, 44100, Ferrara, Italy.
| Abstract |
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Methods We undertook a prospective population-based study in the territory of the 1st, 2nd, 3rd, and 4th local health units in the province of Belluno, an area located in northeast Italy (population, 211 389).
Results In the first year of the study (June 1, 1992, to May 31, 1993), 474 cases of first-ever stroke were registered. The crude annual incidence rate was 2.24/1000 (2.01/1000 for men and 2.45/1000 for women). After adjustment to the European population, the incidence rate for first stroke was 1.70/1000 per year. The pathological diagnosis was confirmed by a CT scan in 89.5% of cases. Cerebral infarction accounted for 319 cases, while 93 patients suffered a primary intracerebral hemorrhage, 12 patients a subarachnoid hemorrhage, and 50 patients a stroke of unknown origin. The overall 30-day case-fatality rate was 33%, and the mortality within the first week from stroke onset was 23%. The recurrence rate after 1 month was 1.9%. After 1 month, 46% of our patients were functionally independent in activities of daily living.
Conclusions Our first-year results confirm the fairly high risk for stroke in central and northern Italy and support European findings regarding risk factors for stroke.
Key Words: epidemiology incidence Italy prognosis
| Introduction |
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| Subjects and Methods |
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All the residents are served by six general hospitals, with two wards of neurology (USLs 3 and 4), 168 general practitioners, and 14 first-aid stations. In every hospital without a neurology ward patients are admitted to internal medicine units and assisted by neurologists operating in the neurological divisions of the province with a weekly service. The local hospitals are also interconnected by a 24-hour helicopter service supplied by an emergency unit.
Diagnostic Criteria
The diagnosis of stroke was defined, according to World Health
Organization criteria, as rapidly developing clinical symptoms and/or
signs of focal, and at times global, loss of cerebral function, with
symptoms lasting more than 24 hours or leading to death, with no
apparent cause other than that of vascular origin.4
Case Collection and Ascertainment
One or more physicians of the wards of neurology, medicine, and
geriatrics of Belluno General Hospital (USL 3), the wards of neurology
and medicine of Feltre General Hospital (USL 4), and the wards of
medicine of the Hospitals of Auronzo and Pieve di Cadore (USL 1),
Agordo (USL 2), and Lamon (USL 4) participated in the study.
All the participant physicians were provided and trained to fill a study protocol for recording data on all suspected patients with acute cerebrovascular disease who were either admitted to their division or were inpatients on other wards. The physicians of the various wards and some of the authors (G.L., M.G., G.F.) organized meetings once every 2 weeks to discuss the case ascertainment of each patient and to state the inclusion of all the new cases in the study. All discharge diagnoses were also reviewed. All general practitioners and first-aid station physicians were notified of the study and asked to refer all suspected cases. All the patients, including those who were treated at home, had a neurological assessment as soon as possible, within 12 hours after the event. This clinical evaluation was repeated 24 hours after the onset of the symptoms to identify the cases of TIA. Both the CT archives present in the study area (USLs 3 and 4) and the death certificates were systematically screened every month to obtain information regarding fatal/nonhospitalized cases or patients who were subsequently transferred to hospitals outside the province. All available medical documents and data were collected, and casebooks for the same patients, from the aforementioned sources, were compared and stored in a computerized database, so that the recruitment of all putative cases would be as complete as possible.
A detailed family and personal history and a thorough neurological examination were conducted on each patient by a study neurologist. A quantitative evaluation that used the Canadian Neurological Scale5 and disability status, determined according to the modified Rankin6 scale7 8 used in the Oxfordshire Community Stroke Project,3 were assessed on admission, every other day during hospitalization, and after 1, 6, and 12 months during the follow-up. Furthermore, during the follow-up all deaths and recurrent strokes were registered.
We recorded clinical and anamnestic information from the patients or from their relatives about the following risk factors: hypertension (anamnestic, on admission, and assessed during the follow-up; >160 mm Hg systolic and >95 mm Hg diastolic on at least two occasions), atrial fibrillation, heart diseases (coronary, valvular, congestive failure), previous TIAs, alcohol abuse (>60 g/d for men and >40 g/d for women), diabetes mellitus, cigarette smoking (regular smoking at the onset of the stroke), hyperlipidemia, peripheral arteriopathies, therapy with anticoagulant drugs (warfarin, heparin), and use of oral contraceptives.
Diagnosis was based on CT findings and cerebrospinal fluid examination (when subarachnoid hemorrhage was suspected). Most patients were submitted to standard blood and urine tests, luetic serology, electroencephalography, 12-lead electrocardiography, and chest roentgenography. Selected groups of patients underwent duplex scanning of cervical vessels, transcranial Doppler scanning of intracerebral arteries, two-dimensional and/or transesophageal echocardiography, 24-hour Holter monitoring, MRI, cerebral angiography, and single-photon emission CT. Other diagnostic studies were performed on an individual basis.
Statistical Analysis
We computed the 95% CIs assuming a Poisson
distribution.9 We calculated the adjusted rates by the
direct method using 10-year age groupings with the European
population10 as a standard. Student's t test
was used to compare the differences between averages and the
z test to compare two rates. Comparisons between frequencies
were evaluated by the
2 test.
Survival curves were obtained by the Kaplan-Meier product limit method11 for the diagnostic groups of intracerebral hemorrhage and cerebral infarction in relation to the onset of stroke. Comparisons between subgroups were evaluated by the log-rank statistic.12 Using this technique, we assessed the effect on survival of stroke-related factors (location and impaired consciousness) and of some risk factors associated with cerebrovascular disease (age, hypertension, heart disease, diabetes mellitus). A multivariate analysis was performed with the use of Cox's proportional hazards model.13
| Results |
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A CT scan was performed within 30 days from onset in 424 patients (89.5%) of the 474 who had suffered a first-ever stroke. Of these 474 patients, 434 (91.6%) were admitted to study area hospitals, 6 (1.3%) were admitted to hospitals outside the province, 29 (6.1%) were treated at home, and 5 (1%) died before admission. Four of these were recruited from information by general practitioners and emergency services files, and only 1 was detected from death certificates. A postmortem examination confirmed the diagnosis in all cases.
The pathological diagnoses for first stroke were as follows: 319 cases of cerebral infarction (67.3%), 91% in the carotid and 9% in the vertebrobasilar territory; 93 cases of intracerebral hemorrhage (19.7%), 80.6% of which were supratentorial and 19.4% infratentorial; and 12 cases of subarachnoid hemorrhage (2.5%). In 50 patients (10.5%) this classification was not possible because neither the CT nor the necropsy data were available (stroke of unknown origin).
The overall annual crude incidence rate for first stroke was 2.24/1000
inhabitants (95% CI, 1.76 to 2.33) (2.01/1000 for men [95% CI, 1.83
to 2.20] and 2.45/1000 for women [95% CI, 2.39 to 3.07]), a
significant difference (z=2.14; P<.05). After
adjustment by the direct method to the European
population,10 the annual incidence rate was 1.70/1000
population. Table 1
shows the age-specific
incidences for first stroke: the rates increase progressively with age,
reaching a maximum at 85 years and older in both sexes. In all except
the group aged 85 years and older, incidence rates were higher for men
than for women; the difference was significant (z=2.90;
P<.01) for those aged 65 to 74 years. The crude incidence
rates according to pathological diagnosis, shown in Table 2
, were 1.50/1000 population for cerebral infarction
(95% CI, 1.33 to 1.68), 0.43/1000 for intracerebral
hemorrhage (95% CI, 0.34 to 0.52), 0.05/1000 for
subarachnoid hemorrhage (95% CI, 0.02 to 0.08), and
0.23/1000 for stroke of unknown origin (95% CI, 0.17 to 0.30). The
incidence rates for cerebral infarction increased with age in both
sexes and were higher for men than for women in each age group except
those aged 85 years and older. When adjusted by the direct method to
the European population,10 the rates decreased to
1.10/1000 for cerebral infarction, 0.33/1000 for
intracerebral hemorrhage, 0.04/1000 for
subarachnoid hemorrhage, and 0.17/1000 for stroke of
unknown origin.
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On admission, we found 235 hypertensive patients (50.8%), excluding
the cases of subarachnoid hemorrhage. However,
hypertension, anamnestic or assessed during the follow-up (>160
mm Hg systolic and >95 mm Hg diastolic on at least two
occasions) was found in 172 patients (54%) with a diagnosis of
ischemic stroke and in 36 patients (39%) with an
intracerebral hemorrhage
(
2=6.068; P=.014), with an overall
proportion of 45%. We noted that almost 50% of anamnestic
hypertensive patients were not following the antihypertensive therapy
with good compliance. The prevalence of atrial fibrillation was
significantly higher (
2=12.924;
P<.0001) in cerebral infarction (77 patients; 24%) than in
intracerebral hemorrhage (6 patients; 7%). A
significantly higher prevalence (
2=5.415;
P=.02) of peripheral arteriopathies was also
found in cerebral infarction (44 patients; 14%) than in
intracerebral hemorrhage (4 patients; 4%).
Fifty-seven patients with a diagnosis of cerebral infarction (18%)
and 24 patients with a diagnosis of intracerebral
hemorrhage (25%) were current cigarette smokers, a
nonsignificant difference. Only 3 patients were oral contraceptive
users. Table 3
shows the prevalence of the other risk
factors.
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The overall 30-day case-fatality rate for patients who had suffered
a first stroke was 33% (158 of 474 patients). A higher mortality was
observed in patients with intracerebral
hemorrhage (34.4%) than in those with cerebral infarction
(26.4%); the difference was not statistically significant. The
mortality rates found in both patients with cerebral infarction and
those with intracerebral hemorrhage were higher
than in those with subarachnoid hemorrhage (8.3%),
with a significant difference (z=2.05, P<.05 and
z=2.53, P<.05, respectively). The mortality
within the first week from onset of symptoms for all the pathological
groups of stroke was 23.2% (110 cases) and again was nonsignificantly
higher in those with primary intracerebral
hemorrhage (20.4%) than in those with cerebral infarction
(17.2%). Finally, 82% of the patients with a stroke of unknown origin
died within the first month and 60% during the first week from the
onset of symptoms. These figures were significantly higher
(P<.01) compared with all the other pathological groups for
both periods used to calculate mortality rates. At 1 month after
stroke, 145 patients (46%) were independent in activities of daily
living (Rankin score,
2), and the recurrence rate was 1.9%
(6 of 316).
The cumulative probability of survival at 30 days
(Figure
) was higher after cerebral infarction than
primary intracerebral hemorrhage
(P<.05). In both patients with a diagnosis of cerebral
hemorrhage and patients with a diagnosis of cerebral
infarction, the probability of survival at 30 days was related to
impaired consciousness on admission (P<.0001). In patients
with cerebral infarction a further relation to atrial fibrillation was
found (P<.001). Increasing age and infratentorial location
adversely affected survival in both groups, but not significantly. We
did not find any sex difference for 1-week and 30-day survival. Other
risk factors, including hypertension, had no significant effect.
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Multivariate analysis confirmed that depressed consciousness on admission significantly adversely affected the prognosis in either primary intracerebral hemorrhage (RR, 10.288; 95% CI, 4.059 to 26.076) or cerebral infarction (RR, 5.737; 95% CI, 3.658 to 8.989). Patients with vertebrobasilar territory infarction had a probability of survival at 1 month that was significantly worse than those with carotid infarction (RR, 2.535; 95% CI, 1.234 to 5.207), while no significant difference in survival emerged between patients with supratentorial and infratentorial hemorrhage. Finally, advancing age was of slight statistical significance (RR, 1.045; 95% CI, 1.018 to 1.071) only in the group of patients with cerebral infarction, while atrial fibrillation lost statistical significance.
| Discussion |
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Diagnostic criteria were applied by a study neurologist as soon as possible, within 12 hours after the stroke. The clinical assessment of all the patients, including those who were cared for at home, was repeated after 24 hours from the onset of the symptoms. In this way we could distinguish between TIA and stroke, and we recruited nine "supposed" cases of TIA as stroke cases. Our collaboration with the wards participating in the study was as good as that with the primary care physicians, and our surveillance of all the mentioned sources was active. Moreover, in the present study the proportion of patients undergoing a CT scan within 30 days from stroke onset was high (89.5%). Similar CT rates were reported in the community-based stroke studies performed in northern Sweden14 (90%) and in Australasia15 (86%). Few stroke registries16 17 used routine CT scanning, but only one, carried out in Dijon, France,18 19 was population-based. In Akita, Japan,16 and in the Lehigh Valley, Pa,17 all the diagnoses were confirmed by CT scanning, but both of these studies were hospital-based. In most of the other population-based studies,3 20 21 22 23 24 25 26 diagnoses were confirmed by CT or necropsy in a more limited number of cases. All these factors as well as the large and well-defined denominator allowed us to meet almost all the criteria proposed by Malmgren et al1 for an ideal stroke incidence study and to provide reliable and comparable results.
In the present study the proportion of nonhospitalized first-ever stroke cases was lower (6.1%) than that reported in other studies. In particular, in the study conducted in Aosta, Italy,22 18% of the patients suffering a first-ever stroke were cared for at home. Higher proportions of patients managed at home by their general practitioners were also reported in the communities of Auckland, New Zealand15 (27.6%); Perth, Australia15 (22%); Copenhagen, Denmark20 (25%); and Oxfordshire, England27 (59%). In contrast, in the first Italian population-based study performed in Umbria21 in 1986 to 1987, the proportion of nonhospitalized patients suffering a first-ever stroke was 8.3%, a figure only slightly higher than that we reported for Belluno. High admission rates were also registered in the studies conducted in Dijon18 (90%); Finland23 (92%); Warsaw, Poland24 (90%); and Malmö, Sweden26 (95%). The high proportion of inpatients registered in these various studies can reflect different admission policies and diverse degrees of public awareness of acute cerebrovascular diseases in addition to disparities in socioeconomic status and the age structure of the population among the various communities. In our experience, because of the easy accessibility of health services even for the people living farther away from hospital facilities, almost all acute stroke patients were referred to the emergency units of the territory or to their general practitioners. Possibly, the presence since 1984 of a section devoted to cerebrovascular diseases inside the Division of Neurology of Belluno General Hospital and the good working relations established over time with the general practitioners and with the physicians operating in the various hospitals of the province contributed to increase the admission rate of first-ever stroke patients.
Our incidence for first-ever stroke was fairly high and supports the rates reported in the other two similar Italian studies. In Umbria, during the period 1986 to 1987 Ricci et al21 found a crude annual incidence rate for first-ever stroke of 2.20/1000 inhabitants, whereas in the survey of the Valle d'Aosta22 during 1989 the corresponding rate was 2.23/1000 population. Hence, our finding confirms no regional variations within central and northern Italy. Similar rates were also found in the community of Copenhagen20 (2.14/1000), Malmö26 (2.25/1000), and Finland23 (2.22/1000). The Oxfordshire Community Stroke Project28 reported an incidence of 1.60 cases of first-ever stroke per 1000 inhabitants, similar to those found in Dijon18 (1.63/1000), Warsaw24 (1.70/1000), and Rochester, Minn29 (1.54/1000; 1980 to 1984).
Since strokes, chiefly cerebral infarction, are most common in those aged 65 years and older in both sexes, differences in incidence rates may reflect dissimilarities in the age structure of the population. In fact, Warsaw24 and Benghazy, Libya,30 where the proportion of people aged 65 years and older (7% and 6%, respectively) was far lower than that of most of the other study populations, had the lowest incidence rates for first-ever stroke. In these studies, only 40% and 62% of stroke patients, respectively, were aged 65 years and older. In contrast, we noted that as many as 75% of stroke cases were in the group aged 65 years and older, as described in other studies18 21 22 28 29 that have identified cases of all ages.
The incidence rates for cerebral infarction and primary intracerebral hemorrhage do not differ substantially from those reported in previous European community-based studies,18 20 23 26 28 31 particularly from those performed in Italy.21 22 We recorded a low proportion of subarachnoid hemorrhage patients, resulting in a rate of 0.05/1000 inhabitants per year. Similar rates were also noted in Umbria21 (0.08/1000), Valle d'Aosta22 (0.05/1000), Malmö26 (0.06/1000), and Oxfordshire28 (0.08/1000), whereas higher rates were reported in Finland23 (0.28/1000) and Akita16 (0.29/1000). The proportion of strokes of unknown origin (10.5%) was lower than that reported in Valle d'Aosta22 (17.7%), Warsaw24 (31%), and Malmö26 (38%), where CT, as in our study, was the only diagnostic criterion. This figure, however, was higher than that found in Umbria21 (7%) and in Oxfordshire28 (4.6%), where in addition to CT, which was performed on a more limited percentage of patients, a diagnostic score was applied. As already reported,3 there is evidence that both community and hospital-based studies that had not used CT extensively had underestimated the incidence of primary intracerebral hemorrhage, particularly of the milder cases. Hence, the 89.5% CT rate either satisfied the original aim of our study or provides reliable results regarding the accuracy of the pathological diagnoses and the interpretation of prognostic data.
Table 4
compares the overall and age- and
sex-specific incidence rates for first-ever stroke reported in
other studies performed throughout the world. Our findings did not
differ substantially from those reported in Oxfordshire28
and fell in the middle of the values previously reported in
Italy.21 22 We noted that the incidence of stroke
increased with age in both sexes and was higher in men than in women in
each age group younger than 85 years. Because the proportion of women
was higher than that of men in the Belluno population, mostly in the
group aged older than 65 years, the overall incidence rate for stroke
was higher in women than in men, even though the difference was not
significant. A similar difference was also described in
Warsaw,24 Malmö,26 and
Oxfordshire,28 whereas other
authors18 20 22 29 30 reported higher incidence rates for
first-ever stroke in men than in women. However, when the same age
groups for men and women were compared, higher incidence rates were
found in men than in women in all except the extreme age group, in
accordance with data previously
published.18 20 22 24 26 28 29 30
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Cerebrovascular disease still represents the most common cause of severe disability in the western world.33 Although epidemiological studies14 29 have shown that stroke mortality has been declining over time, the proportion of people among age groups at higher risk is progressively increasing because of the changing demographic structure. As in most of the communities15 18 21 22 26 28 29 in which epidemiological studies were performed during recent years, we found that more than 75% of the patients were aged 65 years or older. This trend is likely to be strengthened in the future and will have important implications for both social and scientific organizations. Therefore, healthcare facilities should be planned to take into account the changes in the age structure of the population for both the acute treatment of stroke and its secondary complications (eg, aspiration pneumonia, pulmonary thromboembolism, sepsis) and the long-term management of disabilities resulting from stroke. Moreover, as Broderick et al29 emphasized, the potential impact of strict inclusion criteria by age on patient recruitment in stroke therapeutic trials, which are still focused on younger people, would lead to the exclusion of at least 50% of possible candidates.
Regarding prevention, hypertension and heart diseases were the most common risk factors for stroke, supporting data reported in previous studies.15 22 26 30 34 Since stroke can affect blood pressure levels,35 we excluded from the analysis on risk factors the patients who were hypertensive only on admission. In effect, 5.7% of hypertensive patients on admission returned to normal and stable blood pressure levels during the follow-up. The prevalence (54%) of hypertension among the patients with cerebral infarction was similar to those reported in Valle d'Aosta22 (54%) and Oxfordshire36 (52%) but lower compared with that registered in the Framingham Study37 (70%). In contrast to the data found in these studies, hypertension was significantly more frequent in cerebral infarction patients than in cerebral hemorrhage patients. After hypertension, nonvalvular atrial fibrillation was the most common risk factor in patients with cerebral infarction, confirming the consistent association with an increased risk of ischemic stroke assessed in previous prospective studies.38 39 Cigarette smoking is recognized as an important modifiable risk factor for stroke.40 In the present study, 18% of the patients with cerebral infarction and 25% of the patients with primary intracerebral hemorrhage were current smokers at the onset of the disease, resulting in an overall prevalence of 17.5%, a figure similar to those previously reported in other European analyses.22 26 A heavy daily alcohol intake was reported by 15.8% of stroke patients, a proportion slightly lower than that reported in Valle d'Aosta.22 However, comparisons among the various studies are particularly difficult, primarily because of the different alcohol consumption habits in the various countries.
The overall 30-day case-fatality rate (33%) for patients with a diagnosis of first-ever stroke was similar to that reported in Valle d'Aosta22 (31%), East Germany41 (34%), and Espoo-Kauniainen42 (34%) but was higher compared with 19% in Oxfordshire,3 23% in Auckland and Perth,15 21.5% in Dijon,18 18% in Umbria,21 15% in Malmö,26 and 17% in Rochester.29 As expected, the fatality rate in intracerebral hemorrhage patients (34%) was higher than that found in cerebral infarction patients (26%). Nevertheless, among the cases of intracerebral hemorrhage we found fewer deaths than those registered in Oxfordshire3 (50%), Valle d'Aosta22 (47%), and Malmö26 (37%). In contrast, compared with these studies we noted a higher case-fatality rate in patients with a diagnosis of cerebral infarction (26% versus 10%, 13%, and 10%, respectively). These features might represent, at least in part, the consequence of a wider use of CT for either elderly people or mild strokes, which allowed us to allocate cases to the different diagnostic categories with a greater degree of precision.
Prognosis was related to coma on admission in all the pathological groups of stroke, indicating that level of consciousness represents the most important predictor of short-term survival, in agreement with previous studies.22 42 Patients with vertebrobasilar territory infarction fared worse than those with carotid territory infarction in the first month after stroke. A similar finding was reported by Chambers et al43 in the first 10 days after stroke, but by 30 days the difference had disappeared. Furthermore, as already described,43 we found that hypertension had only a weak nonsignificant adverse influence on survival in contrast to data from the Framingham Study,44 which was conducted in the early years of hypertensive therapy.
To summarize, our incidence rates confirm the fairly high risk for stroke in central and northern Italy and support data from other European surveys. Case-fatality rates were somewhat higher compared with other studies throughout the world. We detected that hypertension and heart diseases represent the most common risk factors for stroke, in accordance with other authors.38 43 Finally, we emphasize again the usefulness of a stroke registry as an important tool for both research and epidemiological studies on cerebrovascular disease.
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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Received February 20, 1995; revision received May 5, 1995; accepted June 16, 1995.
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