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(Stroke. 1998;29:126-132.)
© 1998 American Heart Association, Inc.

Original Contributions

Long-term Prognosis After a Minor Stroke

10-Year Mortality and Major Stroke Recurrence Rates in a Hospital-Based Cohort

Massimiliano Prencipe, MD; Franco Culasso, PhD; Maurizia Rasura, MD; Alexia Anzini, MD; Mario Beccia, MD; Marina Cao, MD; Franco Giubilei, MD; Cesare Fieschi, MD

From the Departments of Neurological Sciences (M.P., M.R., A.A., M.B., M.C., F.G., C.F.) and Experimental Medicine (F.C.), University "La Sapienza," Rome, Italy.

Correspondence to Massimiliano Prencipe, MD, Dipartimento di Scienze Neurologiche, Universita degli Studi "La Sapienza," Viale dell'Università 30, 00185 Roma, Italy.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose—Determinants of long-term outcome are not well defined in minor stroke patients. This study aims to evaluate which factors are independent long-term predictors of death and major stroke recurrence in a cohort of minor ischemic strokes.

Methods—A cohort of 322 patients with first-ever minor ischemic strokes (mean age, 55 years; 89% were treated with antiplatelet or anticoagulant drugs) with minor (Rankin score=2) or no disability (Rankin score <2) were followed for 10 years, with only 6% lost to follow-up. Death and major stroke recurrence rates were evaluated by Kaplan-Meier analysis. Hazard ratios and 95% confidence intervals (CI) of factors with P<.1 at the log-rank test were evaluated by multivariate Cox analysis.

Results—The 10-year mortality rate was 32%, with a relative risk of 1.7 (95% CI, 1.4 to 2.1) compared with the age- and sex-matched general population. The 10-year recurrence rate of major strokes was 14%. The hazard ratio (95% CI) of death was 1.1 (1.05 to 1.09) for age (1-year increments), 3.4 (2.2 to 5.2) for minor disability, 1.8 (1.1 to 3.1) for myocardial infarction (MI), 2.0 (1.1 to 3.7) for nonvalvular atrial fibrillation, and 1.8 (1.2 to 2.7) for hypercholesterolemia. The hazard ratio (95% CI) of major stroke recurrence was 2.8 (1.3 to 6.2) for recurrent minor strokes, 3.1 (1.9 to 4.6) for nonlacunar stroke, 2.9 (1.3 to 6.8) for MI, and 3.0 (1.4 to 6.4) for hypertension.

Conclusions—In minor ischemic strokes, age, minor disability, MI, nonvalvular atrial fibrillation, and hypercholesterolemia increase the risk of death; recurrent minor strokes, nonlacunar stroke, MI, and hypertension increase the risk of major stroke.

Key Words: disability • lacunar infarction • long-term survival • stroke, minor • stroke recurrence

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Stroke has a huge impact on public health owing to both the high rate of early mortality and the residual disability of stroke survivors. Furthermore, in the 5 years after a stroke, the risk of dying is 45% to 61%^{1 2 3 4 5} and that of stroke recurrence is 25% to 37%.^{1 5 6 7 8} However, recent data point to a shift in the natural history of stroke toward a less fatal and less disabling disease.^{9 10 11 12} These findings are consistent with hospital-based studies reporting that nearly half of all ischemic stroke patients survive with minor or no deficits.^{2 13 14} Obviously, these minor stroke patients have a cumulative mortality rate that is lower than that of stroke patients taken as a whole owing to the fact that they are not affected by deaths caused by either the initial stroke or the complications of immobility.^{8 15} Furthermore, an overview of published data has shown that stroke recurrence rates are lower in minor than in major stroke patients.¹⁶ Finally, the functional prognosis of these patients would be even less severe if we consider that a consistent part of recurrences consists of minor strokes.^{7 17}

Since few studies have evaluated the long-term prognosis of minor strokes, the determinants of long-term outcome are not well defined in this subset of stroke patients.^{18 19} The aim of the present study was to evaluate the risks of death and major stroke recurrence in a cohort of patients with minor ischemic strokes followed up for 10 years.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The study cohort was recruited from stroke patients consecutively admitted to the Neurological Department of the University of Rome between January 1977 and March 1986. The inclusion criteria were as follows: first-ever stroke; admission within 48 hours of stroke onset; cranial CT scan excluding hemorrhagic or other nonvascular lesions; minor or no disability (stroke-related disability resulting in a score <3 on the modified Rankin scale²⁰ ) within 30 days of stroke onset; no life-threatening diseases within 2 years of discharge; residence in Rome or surroundings; and consent to participate.

Patients were considered as stroke cases only if symptoms or signs lasted longer than 24 hours. We excluded all patients who suffered from deficits caused by new strokes, cerebral angiography, or carotid endarterectomy within 30 days of stroke onset. At discharge, stroke patients were classified as affected by minor disability when stroke symptoms led to some lifestyle restrictions (Rankin=2) or by no disability when stroke symptoms did not interfere with the patient's lifestyle (Rankin <2).

In addition to the cranial CT scan, all patients underwent routine blood tests, ECG, and Doppler sonography (DUD 800 equipment, Delalande AHS) of extracranial vessels. Cerebral angiography was performed in 97 patients selected on a case-by-case basis. Since other examinations (echocardiography, nuclear magnetic resonance, anticardiolipin autoantibodies, and fibrinogen) were performed in only some of the patients (13% to 27%), we did not use these data in the present analysis.

CT scans were performed with a Sireton 2000 scanner, providing 8-mm slices. All the CT scans performed within 72 hours of stroke onset were repeated before patients were discharged, and the second scan was used for the analysis. Patients with inappropriate CT ischemic lesions (located in an area not corresponding to the symptoms of index stroke) or multiple CT ischemic lesions (silent brain infarctions) were not considered first-ever strokes and therefore were excluded. For the purposes of this study, lacunar infarcts were classified as CT lesions with an infarctlike density that were small (<1.5 cm in diameter) and subcortical. CT ischemic lesions not fulfilling these criteria were classified as nonlacunar infarcts. Lacunar strokes were classified as cases presenting a lacunar syndrome²¹ and were associated with a lacunar infarct or a negative CT scan.²² The patients not fulfilling these criteria were classified as having nonlacunar strokes. NVAF, prior MI, and other cardiac diseases were diagnosed on the basis of history, clinical examination, and ECG findings.

We analyzed the following risk factors: arterial hypertension (antihypertensive treatment regularly taken before or after stroke), diabetes mellitus (hypoglycemic treatment taken before or after stroke), and hypercholesterolemia (total fasting serum cholesterol levels 2.4 g/L in men and 2.2 g/L in women, observed on at least two separate occasions). We did not analyze data on smoking and alcohol consumption because data available could not be validated by other means. Furthermore, we analyzed data on history of migraine and use of oral contraceptives in the 6 months preceding stroke.

Follow-up visits included a standardized interview with the patient, a review of the interim medical records, and general and neurological examinations. Patients who did not come to the follow-up visits were contacted by telephone and interviewed according to a standardized questionnaire. When patients were unable to answer or were dead, a family member or a proxy was asked to complete the questionnaire. Both the standardized interview and the telephone questionnaire were aimed at identifying the causes of death and at classifying new cerebral events. Data about the time and cause of death were compared with those written on both the death certificates and medical records available. All patients were followed up at least once a year for 10 years or until they had a major stroke (Rankin grade 3), died, or refused the follow-up visit. Recurrent minor strokes were registered but not considered as an end point. Deaths were classified as follows: stroke deaths were deaths that occurred within 30 days of a recurrent stroke, regardless of the final cause of death; cardiovascular deaths were deaths that occurred within 30 days of a cardiovascular event such as MI, ruptured aortic aneurysm, or other cardiac diseases; in the absence of other evident causes, sudden deaths were considered cardiovascular; nonvascular deaths were those due to other well-defined causes such as cancer, surgery, accidents, or pneumonia; unclassified deaths were those in which the information available was insufficient to classify them.

Mortality rates and stroke recurrence rates were estimated by the Kaplan-Meier method. In the mortality rate analysis, patients suffering from nonfatal major strokes were censored at the time of their new stroke. In the stroke recurrence rate analysis, patients who died from causes other than stroke were censored at the time of their death. Average annual rates were calculated according to the formula suggested by Hankey et al.²³ Relative risk of death was calculated by comparing our mortality rates with those of the age- and sex-matched general population taken from Italian life tables.²⁴ The CI of relative risk was computed by assuming a Poisson distribution. The univariate analysis was performed with the log-rank test. The independent association between each variable and either death or stroke recurrence was estimated by means of the Cox proportional hazard model. We included in the initial model only variables with a log-rank test value of P<.1. This set of variables was reduced by backward elimination until only those significant at P<.05 remained in the model.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Of the 322 stroke patients fulfilling the inclusion criteria, 244 (76%) were men. The median age of participants was 55 years (56 years for men and 53 years for women; Mann-Whitney U test, P=.62). All patients were admitted within 48 hours of stroke onset, and 299 (93%) of them were admitted within 24 hours. The CT scan was negative in 66 (20%) of the 322 patients. Table 1 shows the baseline characteristics of the cohort. The 3 patients with undetermined vascular territory had a negative CT scan. All the patients with either >70% stenosis or occlusion of the symptomatic carotid artery were submitted to cerebral angiography. Nineteen of the 35 patients with stenosis 70% underwent surgery. Four of the 8 carotid occlusion cases were dissections. Of the 115 patients diagnosed as having a lacunar stroke, 36 (31%) had a negative CT scan. Of the 185 patients with no disability at 30 days, 65 (20% of the cohort) had a Rankin score of 0, and 120 (37% of the cohort) had a Rankin score of 1. Among the 16 patients with other cardiac diseases, there were 2 patients with valvular diseases, 5 with first-degree atrioventricular block, and 4 with ventricular and 5 with atrial premature contractions. Seven patients (2 men and 5 women) were affected by migraine. In 5 of these cases other potential causes for ischemic stroke were present as well, and 1 of the 2 remaining patients was taking oral contraceptives. In addition to this patient, 4 other women were taking oral contraceptives when they had the stroke. We did not find any associated disease in 38 patients (12%), 27 of whom were younger than 55 years.

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics of the 322 Patients With Minor Stokes

As shown in Table 2, the proportions of most of the baseline characteristics differ in the four age subgroups. The proportions of men did not differ significantly in these subgroups. In addition to age and sex distribution analysis, we found that the proportion of patients with minor disability was significantly higher (² test, P<.001) in nonlacunar (59%) than in lacunar (13%) strokes. Differences between lacunar and nonlacunar strokes in all the other baseline characteristics were not significant. The proportions of hypertensive subjects were significantly higher in patients with than without minor disability (62% and 48%, respectively; ² test, P=.02), diabetes (72% and 50%, respectively; ² test, P=.005), and hypercholesterolemia (66% and 45%, respectively; ² test, P<.001). Of the 35 patients with prior MI, 23 (66%) were affected by hypertension, 11 (31%) by diabetes, and 16 (46%) by carotid stenosis. Of the 22 NVAF patients, 14 (64%) were affected by hypertension, 6 (27%) by diabetes, 6 (27%) by carotid stenosis, and 1 (5%) by carotid occlusion.

View this table: [in this window] [in a new window]   Table 2. Baseline Characteristics by Age Groups

Of the 322 patients, 242 (75%) were treated with antiplatelet drugs and 27 (8%) with oral anticoagulants, and 19 (6%) were submitted to carotid endarterectomy and subsequently treated with antiplatelet drugs; the remaining 34 patients (11%) did not take oral anticoagulants or antiplatelet drugs because of contraindications or refusal to be treated. Of the 22 NVAF patients, 10 (45%) were chronically treated with oral anticoagulants. Furthermore, both hypertensive and diabetic patients were regularly treated for their disease.

We lost 19 patients (6%), 8 before and 11 after the fifth year of follow-up. The median age was 44 years in lost patients and 56 years in those who completed the follow-up (Mann-Whitney U test, P=.36). There was no difference in the proportion of male participants and male lost patients (76% and 74%, respectively; ² test, P=.9). Twenty-one patients (6.5%) who refused to be visited were interviewed by telephone. Because six of them were unable to answer, the questions were answered by proxy.

By the end of the follow-up period, there were 96 deaths, 39 (41%) due to cardiovascular events (19 were sudden deaths), 24 (25%) to recurrent strokes, 31 (32%) to other diseases (13 caused by cancer), and 2 (2%) to unknown causes. As shown in Fig 1, the 10-year cumulative mortality rate was 32% for stroke patients and 17% for the age- and sex-matched general population. The relative risk between observed and expected deaths was 1.7 (95% CI, 1.4 to 2.1). The average annual mortality rates were 0.4% for the group aged <45 years, 2.4% for the group aged 45 to 54 years, 5.1% for the group aged 55 to 64 years, and 8.1% for the group aged 65 years; the cumulative survival curves stratified according to the four age groups are shown in Fig 2. At the univariate analysis, the risk of death was significantly associated not only with age but also with nonlacunar stroke, minor disability, prior MI, NVAF, hypertension, and diabetes (Table 3). In addition to the variables shown in Table 3, patients with a Rankin score of either 0 or 1 had similar 10-year mortality rates (17% and 19%, respectively; log-rank test, P=.66). For nonlacunar strokes, the 10-year mortality rate was 47% in those with minor disability and 19% in those with no disability (log-rank test, P<.001). For lacunar strokes, the 10-year mortality rate was 69% in patients with minor disability and 18% in those with no disability (log-rank test, P<.001). At the multivariate analysis, the risk of death was significantly and independently associated with age, minor disability, prior MI, NVAF, and hypercholesterolemia (Table 3).

View larger version (18K): [in this window] [in a new window]   Figure 1. Kaplan-Meier survival curves for minor ischemic strokes and age- and sex-matched subjects taken from the general population.

View larger version (21K): [in this window] [in a new window]   Figure 2. Kaplan-Meier survival curves for minor ischemic strokes stratified according to age. Patients suffering from major stroke were censored at the time of stroke.

View this table: [in this window] [in a new window]   Table 3. 10-Year Mortality Rates in 322 Patients With Minor Ischemic Strokes

By the end of the follow-up period, 69 patients had new cerebral events, but only 37 (54%) were major strokes. Of these 37 major strokes, 24 (65%) were fatal, 22 (59%) occurred in the same territory as the first stroke, and 8 (22%) were preceded by a minor recurrence. The major recurrences were ischemic in 18 and hemorrhagic in 1 of the 19 patients who underwent a CT scan. The cumulative 10-year recurrence rate of major strokes was 14%, with an average annual recurrence rate of 1.5%. At the univariate analysis, the risk of stroke recurrence was significantly associated with nonlacunar stroke (Fig 3), recurrent minor strokes, minor disability, prior MI, NVAF, and hypertension (Table 4). The recurrence rate was 11% in the group aged <45 years, 13% in the group aged 45 to 54 years, 14% in the group aged 55 to 64 years, and 17% in the group aged 65 years, but these age-related differences were not statistically significant. At the multivariate analysis, the risk of major stroke recurrence was significantly and independently associated with recurrent minor strokes, nonlacunar stroke, prior MI, and hypertension (table 4).

View larger version (25K): [in this window] [in a new window]   Figure 3. Kaplan-Meier curves of surviving free from major stroke recurrence in lacunar and nonlacunar strokes. Patients who died from causes other than stroke were censored at the time of death.

View this table: [in this window] [in a new window]   Table 4. 10-Year Recurrence Rate of Major Strokes in 322 Patients With Minor Ischemic Strokes

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The present hospital-based cohort consists of first-ever ischemic stroke survivors with minor or no disability within 30 days of stroke onset. These inclusion criteria might explain the high proportion of patients with negative CT scans (20%) and lacunar strokes (36%). The young age of our cohort (median age, 55 years) depends not only on the inclusion criteria used but also on an admission bias, since elderly stroke patients are frequently treated at home or admitted to geriatrics departments. Therefore, the relatively low 10-year cumulative mortality rate observed in this cohort (32%) cannot be directly compared with the rates of studies with different age and inclusion characteristics. Furthermore, 89% of the patients were treated with antiplatelet or anticoagulant drugs, and many patients were taking other drugs for concomitant diseases. However, in our patients aged 65 years, the average annual mortality rate was 8.1%. This figure is comparable to the 4-year cumulative mortality rate of 28% observed in the 30-day stroke survivors of the Lehigh Valley study²⁵ and is marginally lower than the 9.1% observed in the 30-day survivors (mean age, 72 years) in the OCSP study.³ However, the relative risk of death was 1.7 in our cohort as opposed to 2.3 in the 30-day survivors in the OCSP study.³ Since the OCSP study is population-based and our study is hospital-based, the difference between the two studies may partially be explained by our exclusion of patients suffering from severe disability, life-threatening diseases, or multiple vascular brain lesions. Furthermore, our inclusion-exclusion criteria probably reduced the proportion and the severity of the concomitant diseases (exhaustion of susceptibles). Finally, only 7% of the patients in the OCSP study were treated with anticoagulant or antiplatelet drugs.⁷

The average annual stroke recurrence rate observed in our study was extremely low (1.4%). We did not, however, consider as an end point minor stroke recurrences, which accounted for 46% of all stroke recurrences, a figure comparable to the 36% to 52% observed in other studies.^{7 17 26 27} However, even if we had included nondisabling strokes, our annual recurrence rate would have still been lower than the 4% to 9% reported in the literature.^{1 6 7 16} The exclusion of early recurrences, which occur in 3% to 4% of ischemic strokes,^{5 28} would not have affected our rates markedly, given that the average annual rates were calculated over a 10-year follow-up period. To reduce the risk of missing part of stroke recurrences, we interviewed the relatives of all patients who died to identify possible recurrences in the year before their death. Finally, we do not have sufficient data to quantify the effect of preventive therapies, but we may assume that the reduction in the number of recurrences in our cohort is comparable to those achieved in controlled studies.

Despite the relatively low rate of events, the Cox analysis identified some independent predictors of death and major stroke recurrence. We did not find any significant association between sex and either stroke recurrence or death, but these findings have a limited value owing to the small proportion of women (24%) included in our cohort. As expected, age was a strong predictor of death. The lack of a significant association between age and stroke recurrence has been observed in other studies^{6 7 8 28} and supports the hypothesis that strokes and stroke recurrences have different risk factors.

We did not find a significant association between the presence of carotid lesions and either death or stroke recurrence. This may, however, be due to the fact that angiography was performed in only 30% of the patients and that different treatments (surgery, anticoagulants) were administered on a case-by case basis. Consequently, we were unable to evaluate the effect of different carotid lesions on the long-term outcome.

Prior MI was associated with both death and stroke recurrence, confirming the poor prognosis associated with this disease.^{1 25 29 30} Some studies have reported that NVAF is an independent predictor of death,^{25 30} stroke recurrence^{4 31} or both,³² although these findings have not been confirmed by others.^{6 7 17 28} In our cohort, NVAF was significantly associated with death but not with stroke recurrence. However, the high value of the hazard ratio for stroke recurrence (1.9) suggests that the low number of NVAF patients might have provided a false-negative result (type 2 error).

In some studies hypertension was significantly associated with death³¹ or not significantly associated with stroke recurrence.^{7 17 32 33} We instead found, in agreement with other studies, that hypertension was an independent predictor of stroke recurrence, but not of death.^{4 6 25 28}

Diabetes mellitus emerged as a significant predictor of death but not of stroke recurrence in some studies,^{4 25 34} and of stroke recurrence in the Rochester study.⁵ However, in our study, which is in agreement with others,^{1 17} we did not find a significant association between diabetes and either death or stroke recurrence.

Some studies did not find any significant association between hypercholesterolemia and either stroke recurrence or death,^{17 31} but in one statistical overview of 10 prospective studies, the risk of stroke was significantly higher in subjects with hypercholesterolemia than in those without.³⁵ Likewise, a long-term follow-up study found an independent negative association between HDL cholesterol and ischemic stroke mortality.³⁶ In our study we found that hypercholesterolemia increased the risk of death but not of stroke recurrence. This association may be due to the possible role of dyslipidemia as a risk factor in cardiovascular deaths, which accounted for 41% of all deaths in our cohort of relatively young and prevalently male patients.

Our data on disability are in agreement with other studies that found a higher risk of death not only in stroke patients of all types^{37 38} but also in lacunar patients.^{17 39} Since we excluded severely disabled patients, our data suggest that disability may increase the risk of death through mechanisms other than complications caused by immobility. By contrast, the association between disability and stroke recurrence was not present at the multivariate analysis.

Several studies have observed that mortality rates are lower in lacunar than in nonlacunar strokes. This difference could be attributed to the high rate of early deaths observed in nonlacunar strokes. In our study, however, lacunar patients had a better survival even after exclusion of early deaths, although the multivariate analysis did not show a significant association between lacunar strokes and risk of death. The better survival observed in our lacunar strokes could therefore be explained by their strong inverse association with disability. In the Stroke Data Bank, lacunar strokes had 2-year recurrence rates that were similar to those of embolic strokes (14.6 and 14.7, respectively) but lower than those of atherosclerotic strokes (21.9).²⁸ In the Rochester population, lacunar and nonlacunar patients had a similar probability of stroke recurrence.⁴⁰ We found a significant inverse association between lacunar strokes and major stroke recurrences. Therefore, our data are consistent with the hypothesis that lacunar and nonlacunar strokes have a different pathogenesis.

In conclusion, these findings cannot be automatically applied to the whole population of stroke patients, but they can provide useful information on the outcome of a highly selected and treated cohort of minor strokes. Despite our selection criteria and the best treatment available, our patients had a risk of death 1.7 times higher than that of the age- and sex-matched general population. The unexpected association between death and both minor disability and hypercholesterolemia suggests that these factors should receive more attention in future studies on long-term outcome. Finally, our data on stroke recurrence emphasize the importance of a differential diagnosis both between major and minor recurrences and between lacunar and nonlacunar strokes.

	Selected Abbreviations and Acronyms

 

CI = confidence interval MI = myocardial infarction NVAF = nonvalvular atrial fibrillation OCSP = Oxfordshire Community Stroke Project

	Acknowledgments

 
This study was supported by a grant from the National Research Council (CNR- 95.01021.PF40). The authors thank Lewis Baker for his assistance in preparing the manuscript.

Received July 16, 1997; revision received October 13, 1997; accepted October 13, 1997.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 
1. Sacco RL, Wolf PA, Kannel WB, McNamara PM. Survival and recurrence following stroke: the Framingham study. Stroke. 1982;13:290–295.[Abstract/Free Full Text]

2. Kojima S, Omura T, Wakamatsu W, Kishi M, Yamazaki T, Iida M, Komachi Y. Prognosis and disability of stroke patients after 5 years in Akita, Japan. Stroke. 1990;21:72–77.[Abstract/Free Full Text]

3. Dennis MS, Burn JPS, Sandercock PAG, Bamford JM, Wade DT, Warlow CP. Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project. Stroke. 1993;24:796–800.[Abstract/Free Full Text]

4. Lai SM, Alter M, Friday G, Sobel E. A multifactorial analysis of risk factors for recurrence of ischemic stroke. Stroke. 1994;25:958–962.[Abstract]

5. Petty GW, Brown RD, Sicks JR, O'Fallon WM, Whisnant JP. Survival and recurrence after first cerebral infarction in Rochester, Minnesota, 1975–1989. Cerebrovasc Dis. 1996;6(suppl 2):6–7.

6. Viitanen M, Eriksson S, Asplund K. Risk of recurrent stroke, myocardial infarction and epilepsy during long-term follow-up after stroke. Eur Neurol. 1988;28:227–231.[Medline] [Order article via Infotrieve]

7. Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Long-term risk of recurrent stroke after a first-ever stroke: the Oxfordshire Community Stroke Project. Stroke. 1994;25:333–337.[Abstract]

8. Bamford J, Dennis M, Sandercock P, Burn J, Warlow C. The frequency, causes and timing of death within 30 days of a first stroke: the Oxfordshire Community Stroke Project. J Neurol Neurosurg Psychiatry. 1990;53:824–829.[Abstract/Free Full Text]

9. Ahmed OI, Orchard TJ, Sharma R, Mitchell H, Talbot E. Declining mortality from stroke in Allegheny County, Pennsylvania. Trends in case fatality and severity of disease, 1971–1980. Stroke. 1988;19:181–184.[Abstract/Free Full Text]

10. Howard G, Toole JF, Becker C, Lefkowitz DS, Truscott BL, Rose L, Evans GW. Changes in survival following stroke in five North Carolina counties observed during two different periods. Stroke. 1989;20:345–350.[Abstract/Free Full Text]

11. Bonita R, Broad JB, Beaglehole R. Changes in stroke incidence and case-fatality in Auckland, New Zealand, 1981–91. Lancet. 1993;342:1470–1473.[Medline] [Order article via Infotrieve]

12. Barker WH, Mullooly JP. Stroke in a defined elderly population, 1967–1985: a less lethal and disabling but no less common disease. Stroke. 1997;28:284–290.[Abstract/Free Full Text]

13. D'Alessandro G, Di Giovanni M, Roveyaz L, Iannizzi L, Pesenti Compagnoni M, Blanc S, Bottacchi E. Incidence and prognosis of stroke in the Valle d'Aosta, Italy: first-year results of a community-based study. Stroke. 1992;23:1712–1715.[Abstract/Free Full Text]

14. Lauria G, Gentile M, Fassetta G, Casetta I, Agnoli F, Andreotta G, Barp C, Caneve G, Cavallaro A, Cielo R, Mongillo D, Mosca M, Olivieri PG. Incidence and prognosis of stroke in the Belluno province, Italy: first-year results of a community-based study. Stroke. 1995;26:1787–1793.[Abstract/Free Full Text]

15. Sacco RL, Shi T, Zamanillo MC, Kargman DE. Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community: the Northern Manhattan Stroke Study. Neurology. 1994;44:626–634.[Abstract/Free Full Text]

16. Wilterdink JL, Easton JD. Vascular event rates in patients with atherosclerotic cerebrovascular disease. Arch Neurol. 1992;49:857–863.[Abstract/Free Full Text]

17. Salgado AV, Ferro JM, Gouveia-Oliveira A. Long-term prognosis of first-ever lacunar strokes: a hospital-based study. Stroke. 1996;27:661–666.[Abstract/Free Full Text]

18. Dennis MS, Bamford JM, Sandercock PAG, Warlow CP. A comparison of risk factors and prognosis for transient ischemic attacks and minor ischemic strokes: the Oxfordshire Community Stroke Project. Stroke. 1989;20:1494–1499.[Abstract/Free Full Text]

19. Kappelle LJ, van Latum JC, van Swieten JC, Algra A, Koudstaal PJ, van Gijn J. Recurrent stroke after transient ischaemic attack or minor ischaemic stroke: does the distinction between small and large vessel disease remain true to type? J Neurol Neurosurg Psychiatry. 1995;59:127–131.[Abstract/Free Full Text]

20. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJA, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–607.[Abstract/Free Full Text]

21. Bamford J, Sandercock P, Jones L, Warlow C. The natural history of lacunar infarction: the Oxfordshire Community Stroke Project. Stroke. 1987;18:545–551.[Abstract/Free Full Text]

22. Gan R, Sacco RL, Kargman DE, Roberts JK, Boden-Albala B, Gu Q. Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke Study experience. Neurology. 1997;48:1204–1211.[Abstract/Free Full Text]

23. Hankey GJ, Slattery JM, Warlow CP. The prognosis of hospital referred transient ischaemic attacks. J Neurol Neurosurg Psychiatry. 1991;54:793–802.[Abstract/Free Full Text]

24. Istituto Nazionale di Statistica (ISTAT). Cause di Morte: Anno 1988. Rome, Italy: ISTAT; 1991;4:1–400.

25. Lai SM, Alter M, Friday G, Sobel E. Prognosis for survival after an initial stroke. Stroke. 1995;26:2011–2015.[Abstract/Free Full Text]

26. Soelberg Sorensen P, Marquardsen J, Pedersen H, Heltberg A, Munck O. Long-term prognosis and quality of life after reversible cerebral ischemic attacks. Acta Neurol Scand. 1989;79:204–213.[Medline] [Order article via Infotrieve]

27. Dennis M, Bamford J, Sandercock P, Warlow C. Prognosis of transient ischemic attacks in the Oxfordshire Community Stroke Project. Stroke. 1990;21:848–853.[Abstract/Free Full Text]

28. Hier DB, Foulkes MA, Swiontoniowski M, Sacco RL, Gorelick PB, Mohr JP, Price TR, Wolf PA. Stroke recurrence within 2 years after ischemic infarction. Stroke. 1991;22:155–161.[Abstract/Free Full Text]

29. Candelise L, Vigotti M, Fieschi C, Brambilla GL, Bono G, Conforti P, De Zanche L, Inzitari D, Mariani F, Prencipe M, Argentino C, Passero S. Italian multicenter study on reversible cerebral ischemic attacks, VI: prognostic factors and follow-up results. Stroke. 1986;17:842–848.[Abstract/Free Full Text]

30. Broderick JP, Phillips SJ, O'Fallon WM, Frye RL, Whisnant JP. Relationship of cardiac disease to stroke occurrence, recurrence, and mortality. Stroke. 1992;23:1250–1256.[Abstract/Free Full Text]

31. Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Stroke recurrence: predictors, severity, and prognosis: the Copenhagen Stroke Study. Neurology. 1997;48:891–895.[Abstract/Free Full Text]

32. Lin HJ, Wolf PA, Kelly-Hayes M, Beiser AS, Kase CS, Benjamin EJ, D'Agostino RB. Stroke severity in atrial fibrillation: the Framingham Study. Stroke. 1996;27:1760–1764.[Abstract/Free Full Text]

33. Alter M, Friday G, Lai SM, O'Connel J, Sobel E. Hypertension and risk of stroke recurrence. Stroke. 1994;25:1605–1610.[Abstract]

34. Clavier I, Hommel M, Besson G, Noèlle B, Ferjus Perret JE. Long-term prognosis of symptomatic lacunar infarcts: a hospital-based study. Stroke. 1994;25:2005–2009.[Abstract]

35. Qizilbash N, Duffy SW, Warlow C, Mann J. Lipids are risk factors for ischaemic stroke: overview and review. Cerebrovasc Dis. 1992;2:127–136.

36. Tanne D, Yaari S, Goldbourt U. High-density lipoprotein cholesterol and risk of ischemic stroke mortality: a 21-year follow-up of 8586 men from the Israeli ischemic heart disease study. Stroke. 1997;28:83–87.[Abstract/Free Full Text]

37. Marquardsen J. The natural history of acute cerebrovascular disease: a retrospective study of 769 patients. Acta Neurol Scand Suppl. 1969;45(suppl 38):11–155.

38. Bonita R, Ford MA, Stewart AW. Predicting survival after stroke: a three-year follow-up. Stroke. 1988;19:669–673.[Abstract/Free Full Text]

39. Gandolfo C, Moretti C, Dall'Agata D, Primavera A, Brusa G, Loeb C. Long-term prognosis of patients with lacunar syndromes. Acta Neurol Scand. 1986;74:224–229.[Medline] [Order article via Infotrieve]

40. Sacco SE, Whisnant JP, Broderick JP, Phillips SJ, O'Fallon WM. Epidemiological characteristics of lacunar infarcts in a population. Stroke. 1991;22:1236–1241.[Abstract/Free Full Text]

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