(Stroke. 2001;32:52.)
© 2001 American Heart Association, Inc.
Original Contributions |
Stroke in Young Adults in the Community-Based L’Aquila Registry
Incidence and Prognosis
From the Department of Neurology, University of L’Aquila, L’Aquila, Italy.
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Abstract |
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Background and Purpose—Stroke type in the young may influence the outcome and may have a dramatic impact on the quality of life in survivors. This study aimed to evaluate the incidence and prognosis of first-ever stroke in the young and to make comparisons with older patients within a well-defined population.
Methods—All first-ever strokes occurring in the L’Aquila district, central Italy, were traced by active monitoring of inpatient and outpatient health services. Incidence rates were standardized to the 1996 European population according to the direct method. Long-term survival was estimated by the Kaplan-Meier method; outcome in survivors was evaluated by the modified Rankin scale.
Results—Of 4353 patients who had a first-ever stroke, 89 patients <45 years of age (55 men and 34 women) (2%) were identified in a 5-year period. Mean age±SD was 36.1±8.1 years. Twenty patients (22.5%) had a subarachnoid hemorrhage, 18 (20.2%) an intracerebral hemorrhage, and 51 (57.3%) a cerebral infarction. The corresponding proportions in patients >45 years of age were 2.4%, 13.3%, and 83.1%. Neuroimaging studies of the brain detected 14 intracranial aneurysms and 6 arteriovenous malformations in 20 of 38 patients (52.6%) with either subarachnoid (n=17) or intracerebral (n=3) hemorrhage. The crude annual incidence rate was 10.18/100 000 (95% CI, 8.14 to 12.57) and 10.23/100 000 when standardized to the 1996 European population. The 30-day case-fatality rate was 11.2% (95% CI, 6.2 to 19.4). Patients with subarachnoid hemorrhage had the highest proportion of good recovery (60%), patients with intracerebral hemorrhage had the highest mortality (44%), and patients with cerebral infarction had the highest proportion of severe disability (47%).
Conclusions—Stroke patients <45 years of age showed a disproportionate cumulative high prevalence (42.7%) of subarachnoid and intracerebral hemorrhage with respect to older patients (15.7%), mainly (52.6%) due to aneurysms and arteriovenous malformations. Therefore, screening procedures and preventive strategies in the young should also be addressed to subjects at risk of subarachnoid and intracerebral hemorrhage.
Key Words: incidence • prognosis • stroke • young adults
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In Western countries, <5% of all strokes occur in subjects <45 years of age.1 Higher proportions, between 19% and 30%, were reported in developing countries.2 3 Stroke incidence rates in the young were reported by few surveys and were rarely assessed by community-based studies with adequate methodology.1 3 4 5 6 7 8 9 10 Moreover, reported incidence rates had wide CIs because of the small number of incident cases in the young.1 3 4 5 6 7 8 9 10
This study aimed to evaluate the incidence and prognosis of first-ever stroke in the young and to make direct comparisons with patients in the older age group within a well-defined population.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Study Design
The prospective community-based registry of stroke patients residing in the L’Aquila district, central Italy, started on January 1, 1994, and ended on December 31, 1998.11 Stroke was defined as rapidly developing signs of focal or global disturbance of cerebral function, lasting >24 hours or leading to death, with no apparent cause other than that of vascular origin (codes 430 to 434 and 436 to 437, International Classification of Diseases, 9th Revision [ICD-9]).11 12 Codes of the Application of the International Classification of Diseases to Neurology (ICD-10 NA) were also applied to patients who had neuroimaging studies of the brain to define stroke types and pathogenic mechanisms.13 Study population and methodology were detailed elsewhere.11
Among a total resident population of 297 838 individuals, 174 875 (58.7%) were <45 years of age. The proportion of subjects in this age group was stable (+1%) between 1981 and 1991.14 Because of the wide availability of health services in the district, nearly all young stroke patients included in the registry were probably referred to hospitals. All subjects were followed up with quarterly planned visits or a complete phone interview with the patient or the next of kin when appropriate, by means of a semistructured questionnaire, up to June 30, 2000. Outcome events were represented by nonfatal or fatal stroke recurrence and death from either cardiovascular or noncardiovascular causes. Functional outcome was evaluated by means of the modified Rankin scale (mRS) and considered as recorded at the last available follow-up visit.15 The mRS is a 7-point scale that assesses overall function and mortality, because patients who die are scored with the worst possible score (6) in this scale. In the present study, patients were regarded as having a good recovery when the score was between 0 and 2 and severe disability when the score was between 3 and 5.
Statistical Analysis
Average crude incidence rates were calculated over
the study period. Ninety-five percent CIs for incidence rates were
calculated assuming the Poisson
distribution.16 The expected
number of patients missed by all the case-finding sources was estimated
by a log-linear model including inpatient, outpatient, and death
certificate sources, together with their second-order interaction
terms.11 17 All
data used for comparisons were standardized for age and sex by the
direct method to the 1996 European
population.18 Student’s
t test was used to compare
group means. Survival after stroke was estimated by the Kaplan-Meier
method, and comparisons among stroke types were performed by means of
the log-rank test. Two-sided values of
P<0.05 were considered to
indicate statistical
significance.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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During the study period, we identified 171 patients <45 years of age with clinical signs attributable to stroke. After comprehensive evaluation, 82 patients were excluded because of stroke due to head trauma (n=55; 67%), residence out of the district (n=17; 21%), perinatal intracerebral hemorrhage (n=3; 4%), transient ischemic attack (n=6; 7%), and recurrent stroke (n=1; 1%). The proportion of first-ever strokes in subjects <45 years of age was 2%, ie, 89 of 4353 patients. Fifty-five were men (61.8%) and 34 women (38.2%); mean age±SD was 36.1±8.1 years. It was estimated that
2 patients (2.2%) were missed by the
capture-recapture technique. All patients but 1 were hospitalized,
either within (n=79) or out of the district (n=9). Mean duration of
hospital stay was shorter
(P=0.03) in subjects <45 years
of age (10.4±11.4 days) than in those >45 (13.0±10.6 days). All
patients underwent brain CT (n=63), MRI (n=22), or both (n=4) at least
once. Mean duration of follow-up was 49.7 months (range, 19.2 to 78.9
months).
Table 1
shows the distribution of stroke types
according to the ICD-9 compared with the ICD-10 NA classification.
Twenty patients (22.5%) had a subarachnoid hemorrhage,
18 (20.2%) an intracerebral hemorrhage, and 51
(57.3%) a cerebral infarction. The corresponding proportions for
patients >45 years old were 2.4%, 13.3%, and 83.1%, with 1.2% of
ill-defined cerebrovascular disease. The cumulative proportion of
patients with subarachnoid and intracerebral
hemorrhage was 42.7% in patients <45 years of age and 15.7%
in patients >45 years. In 20 of 38 young patients (52.6%) with either
subarachnoid (n=17) or intracerebral (n=3)
hemorrhage, neuroimaging studies of the brain detected 14
intracranial aneurysms and 6 arteriovenous
malformations.
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In patients <45 years of age
(Table 2), the crude annual incidence rate of first-ever
stroke was 10.18/100 000 (95% CI, 8.14 to 12.57). Incidence rates
increased steeply with age, with 30.3% of the events occurring in
patients <35 years of age. Annual crude incidence rates were
2.29/100 000 for subarachnoid hemorrhage,
2.06/100 000 for intracerebral hemorrhage, and
5.83/100 000 for cerebral infarction. The incidence rate was
10.23/100 000
(Table 3) when standardized by age and sex to the 1996
European population and was within the range of the rates reported in
comparable registries (9.7 to 13.8/100 000).
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Ten patients died within 30 days of stroke onset. Six were
men and 4 women; 7 patients had an intracerebral and
3 a subarachnoid hemorrhage; 9 were comatose since
stroke onset; and 5 had arterial hypertension and 4
diabetes mellitus. The 30-day case-fatality rate was 11.2% (95% CI,
6.2 to 19.4). The 1-year case-fatality rate did not change because of
the absence of any further event. The 30-day case-fatality rate for
patients >45 years was 25.0%. Long-term survival was better in
patients <45 years of age (n=89) than in those >45 years (n=4264)
(P<0.0001; log-rank test)
(Figure 1). One patient who had recovered from an
intracerebral hemorrhage died of pneumonia
after 3 years, and 1 patient who suffered a cerebral infarction had a
nonfatal stroke recurrence after 3 months.
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The long-term functional outcome evaluated by means of the
mRS varied according to stroke type
(Figure 2). Patients with subarachnoid
hemorrhage had the highest proportion of good recovery (n=10;
60%), with a mortality rate of 15% (n=3); patients with
intracerebral hemorrhage had the highest
mortality (n=8; 44%) and the lowest proportion of severe disability
(n=3; 17%); and patients with cerebral infarction had the highest
proportion of severe disability (n=24; 47%) and no
deaths.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In subjects <45 years of age, the annual crude incidence rate of first-ever stroke was low (10.18/100 000). The cumulative proportion of patients with subarachnoid and intracerebral hemorrhage was higher (42.7%) than in patients >45 years of age (15.7%).1 5 19 The 30-day case-fatality rate was lower (11.2%) than in patients >45 years of age (25.0%). Intracerebral hemorrhage was associated with the highest mortality, and cerebral infarction was associated with the most severe disability.19 20 Hospital stay was shorter for the younger (10.4 days) than for the older (13.0 days) patients because of less comorbidity and different distribution of the stroke types.20
The strength of the present study relies on the inclusion of a number of cases allowing precise estimates of incidence and outcome of stroke in the young within a well-defined and stable population. Thoroughness of case ascertainment, together with a very high rate of hospitalization of the young patients, allowed unbiased diagnoses and comprehensive follow-up.11 Nevertheless, the number of patients included might have been too small to analyze associations with more rare risk factors and comorbid conditions. In addition, because the study was designed as a community-based study, the diagnostic protocol did not evaluate uncommon stroke causes. Any exhaustive investigation of pathogenetic determinants was beyond the scope of the study.
In comparisons with other studies, our incidence rate was within the range of comparable registries from Western countries (9.7 to 13.8/100 000) that used a similar methodology and included patients in the same age range6 7 8 9 10 and within the range of most of the other studies.1 3 4 5 20 Higher rates were reported by a few studies with less accurate identification of the study population.2 21 22 The cumulative proportion of subarachnoid and intracerebral hemorrhage in young patients, although high (42.7%), was within the range found in previous studies (33.3% to 57.5%).1 5 6 7 8 9 10 The prevalence of aneurysms and arteriovenous malformations in patients with subarachnoid and intracerebral hemorrhage was also relevant (52.6%), although in the range reported by other studies (49% to 75%).1 5 19
Stroke was a rare event in the young; the annual incidence rate was 10.18/100 000, representing 2% of all strokes. Stroke was even rarer in patients <35 years old; only 30.3% of our young patients with a first-ever stroke belonged to this age group. However, because of the longer expected survival at this age, young patients accounted for as much as 20% of the years of potential life lost because of the stroke.23 The high proportion of subarachnoid and intracerebral hemorrhages in patients <45 years old mandates tailored preventive strategies. In addition, because 52.6% of the subarachnoid and intracerebral hemorrhages were due to aneurysms or arteriovenous malformations, some events might have been prevented by means of invasive and expensive screening strategies applied to asymptomatic patients.24 Screening protocols that focused on the relatives of patients who suffered from subarachnoid hemorrhage might potentially be cost-effective.25 It is worth mentioning the exclusion from our study of a relevant number of patients who suffered a stroke related to head trauma.
Although the 30-day case-fatality rate in patients <45 years of age was less than half of that reported in patients >45 years (11.2% versus 25.0%), stroke in the young does not represent a benign event.23 The role of arterial hypertension in comatose patients with early death might have depended on previous reduced compliance with antihypertensive treatment, whereas any interpretation of the role of diabetes mellitus requires further study. As already shown, however, stroke type was the most important predictor of mortality. In addition, it should be emphasized that in our study, the low case-fatality rate was attributable primarily to the lack of short- and long-term mortality in young patients with cerebral infarction. Disability after the first stroke was inversely related to mortality, at variance with other studies.20
The question of whether appropriate diagnostic procedures might identify a larger proportion of subjects at risk of subarachnoid and intracerebral hemorrhage remains unanswered and should be addressed by future research. Nevertheless, the proper identification and evaluation of factors that might influence outcome and especially return to work after stroke is mandatory to reduce the global burden of this disease, which, although rare, maintains a relevant social impact in the young.
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Acknowledgments |
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This study was supported by a grant (CNR 96.03027.CT04) from the Consiglio Nazionale delle Ricerche, Rome, Italy.
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Footnotes |
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Reprint requests to Carmine Marini, MD, Clinica Neurologica, Dipartimento di Medicina Interna e Sanità Pubblica, Università degli Studi di L’Aquila, 67100 L’Aquila-Coppito, Italy.
Received August 10, 2000; revision received September 11, 2000; accepted September 20, 2000.
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