Author:
Ashraf Shehatah

Correspondence:
Dr. Ashraf Shehatah
Consultant Internist Geriatrician
MBBC, MSc, DPN, DPP, MD
Mobile: +966 508030779
Email : alshehatah@hotmail.com

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INTRODUCTION

Stroke is caused by disruption of blood circulation in the brain and represents the leading cause of neurologic disability in the elderly (1), (2), (3). As the proportion of the elderly in the population is expected to dramatically increase, studies regarding the effect of age on different medical diseases and conditions are necessary to determine appropriate management. Stroke incidence has declined in persons aged younger than 75 years (4), but prevalence is still high in elderly patients; and stroke represents one of the leading causes of death in this population (5). However, data regarding diagnostic and management decisions in older patients who present with signs and symptoms of stroke are scarce.

Previous reports showed differences in management concerning computed tomographic (CT) scan use and care access(6) and treatments including antithrombotic and lipid-lowering agents(7). In practice, the best criteria of stroke management include new parameters (time before medical care, magnetic resonance imaging [MRI], and thrombolysis) that were not considered at that time. To our knowledge, no reported study has previously investigated the effect of age on stroke management in an urban teaching hospital.

In Saudi Arabia, most of strokes in elderly patients are referred to an emergency department (ED). The aim of the present study was to analyze the effect of age on management and prognosis of stroke, and to identify factors affecting stroke survival in elderly patients referred initially to an ED. Time to be seen by a physician, CT scan and MRI use, antithrombotic and thrombolysis agents use, care and in particular access to a stroke center were the variables used to assess stroke management. Length of stay, autonomy, 3-month hospital-free days, and in-hospital and 1-year mortality were the outcome measures of interest.

MATERIAL AND METHODS
The study was designed as a prospective study performed during a period from January 2009 to July 2009 to analyze age influence on stroke management and prognosis in elderly patients admitted to an ED with a diagnosis of stroke. In 2010, we completed this study to determine patient outcome, including autonomy and death. In compliance with hospital law, this observational study needed approval from the continuous medical education committee (equivalent to the ethical review Board). We included all consecutive patients with acute stroke admitted to the ED of a 250-bed urban hospital. All patients presenting with primary diagnosis of stroke were included in our cohort. Primary diagnosis of stroke was defined as rapidly developing signs of focal or global disturbance of cerebral function either transient or lasting for more than 24 hours, or leading to death, with no apparent cause other than that of vascular origin (8),(9).

For every patient, medical care by the physician in charge included medical history, especially cardiovascular risk factors, previous neurologic, cognitive and cardiac diseases, living conditions (home living, institution), autonomy (daily help, and daily activity, using the validated Activities of Daily Living scale [ADL](10)), physical examination, and brain imaging. Autonomy, as ascertained by questionnaire, was defined as an ADL score = 6. Hypertension was considered present if a patient had known hypertension or treatment of hypertension at admission. Diabetes was considered present if a patient had known diabetes or treatment of diabetes on admission. History of atrial fibrillation was considered present if present on the electrocardiogram at admission. Diagnosis of stroke was performed according to the World Health Organization definition, using clinical and imaging data from ED and discharge units including neurologic, geriatric, and other units. Data sources were obtained from complete ED medical charts of patients admitted for suspicion of stroke, hospitalization reports, and medical charts from all health care services. Stroke severity was assessed at admission using the validated modified Rankin scale because of its feasibility in ED (11). All final diagnoses were performed according to in-hospital management and final conclusions before out-hospital discharge of patients. Patients were compared according to their age; those younger than 75 years classified into the younger group and those 75 years or older into the older group.

2.1 Management analysis
Criteria were chosen for management analysis, including time to be seen by a physician in the ED; emergency stroke center admission; emergency brain imaging including CT scan and MRI; treatments including antithrombotic, anticoagulant treatment and fibrinolysis; and admission after ED to neurologic, geriatric, or intensive care unit. All decisions were made by the emergency physician according to standard clinical practice. All events occurring in the study population were identified by monitoring of all inpatient health services. After hospitalization report analysis, missing data were obtained from the complete patient chart.

2.2 Outcome analysis
We determined the length of stay in the hospital and in-hospital mortality. To enable us to compare the length of hospitalization between the 2 groups while taking into account the deaths, we calculated the number of hospital-free days during the 3-month period after admission to the ED, all dead patients being scored 0 hospital-free days, as previously described (12). In 2010, to analyze the outcome for each living patient after stroke discharge, a phone call and a written questionnaire to the patient him or herself or to the family or caregiver, was used. This questionnaire, including parameters about autonomy (home living, need for help, institution, daily living activities) and evolution (any new admission) during the year after stroke, was administered. At this stage, we obtained information on ADL status for demented patients from the correspondents.

Data are expressed as number of patients (percentage) and mean ± SD for normally distributed variables, and median and 95% confidence interval (CI) for non normally distributed variables (Kolmogorov-Smirnov test). We used single-entry data methods. Comparison of proportions was performed using the X 2 test or the Fisher exact method; comparison of 2 means was performed using the Student t test, and comparison of 2 medians was performed using the Mann-Whitney test. Survival was estimated by the Kaplan-Meier method, and differences in survival between groups was assessed by the log-rank test. For subgroup analysis, the Bonferroni correction was applied to the log-rank test.

Univariate and multivariate Cox proportional-hazards models were used to determine variables associated with stroke death within 1 year after admission. To avoid over-fitting, we used a conservative approach and included only the significant variables in the univariate analysis (P value of entry <.10). The type of stroke was entered as hemorrhagic vs ischemic, the reference being a transient stroke. Interactions were not tested. The Spearman coefficient matrix correlation was used to identify significant colinearity (>0.70) between variables. A backward-elimination model was applied. The hazards ratio and the 95% CI of variables selected by the Cox model were calculated. Then we compared the adjusted estimates of survival between young and elderly patients. All P values were 2-tailed, and a P value of less than .05 was considered significant. Statistical analysis was performed using NCSS 2004 (Statistical Solutions Ltd, Corve, Ireland).
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RESULTS
During the study period, we identified 253 patients in our ED with a suspected stroke. After the exclusion of 47 patients (19%) with a diagnosis other than stroke (n = 29) and without final diagnosis (n = 18), 206 patients met the inclusion criterion and were included in our study with a final diagnosis of stroke.

Baseline characteristics are represented in Table 1. Hypertension, atrial fibrillation, coronary artery disease, dementia, and antithrombotic or anticoagulant treatment were significantly more frequent in elderly patients, but tobacco smoking was significantly less observed. Symptom duration was significantly different between the younger and older groups, but there was no significant difference for patients arriving before 3 hours after the onset of stroke (P = .63). Type of stroke (ischemic or hemorrhagic) was similar between groups (Table 1).

3.2 Outcome and survival analysis
Regarding living conditions, information was available for 100 (99%) younger patients and all older patients at baseline (Table 1), and for 86 (100%) surviving young patients and 72 (96%) surviving old patients after 1 year (Table 2). Regarding ADL and autonomy-free results, information was available for 65 (64%) younger patients and 56 (53%) older patients at baseline (Table 1) and for 55 (64%) surviving younger patients and 52 (69%) surviving older patients (Table 2). At baseline, older patients were less frequently living at home with a significant higher value for disabilities on the ADL score and there were a lower number of autonomy-free patients. After 1 year, only 51% of older patients were still living at home, compared to 92% in the younger group (P < .001), and ADL score and autonomy-free patients in this group worsened (Table 2).

After admission, length of stay was longer in older patients (P = .008); in-hospital mortality tended to be higher in older patients (12% vs. 6%, nonsignificant); and the 3-month post discharge, hospital-free days period was shorter in older patients (P = .002).

At the time of analysis, 14 patients in the younger group and 28 patients in the older group had died. The 1-year mortality rate after diagnosis of stroke was 16% in younger patients (95% CI, 8-25%) compared with 33% in older patients (95% CI, 23%-43%) (P = .014, Fig.1). Compared with the expected mortality in the general population in Saudi Arabia, the mortality in our study cohort was significantly higher in both older (27% vs. 11%, P < .01) and younger (14% vs. 1%, P < .001) patients or when considering the whole cohort (20% vs. 12%, P < .001).

Figure 1: Kaplan-Meier estimates of death in patients aged < or >75 years (P = .014). Time zero is the onset of the stroke. Curves show survival considering all deaths from any cause.

3.3 Predictors of mortality
Comparison between deceased and living patients is shown in Table 3. In the multivariate analysis, hemorrhagic stroke, dementia, and a high Rankin score were independent positive predictors of 1-year mortality (Table 4).

Table 3: Comparison between deceased and survivors 1 year after admission

Data are expressed as number of patients (percentage), mean ± SD, or median (95% CI). P values are for the comparison of living patients with deceased patients and were calculated using the unpaired Student t test, the Mann-Whitney test, the X 2 test or Fisher exact method, as appropriate. Hazards ratio with corresponding 95% CI were calculated using univariate Cox regression analysis and are for the comparison of living patients with deceased patients.

Table 4: Multivariate Cox proportional-hazards analysis of variables associated with death within 1 year after admission for stroke

Because data for Rankin were missing for some patients, the final sample used in the multivariate analysis consisted of 179 patients, 36 (20%) of whom died.

DISCUSSION
Very few studies have included elderly patients with a mean age of 75 years or older (6),(7),(14),(15),(16),(17),(18),(19),(20),(21), particularly in the ED where most elderly patients with acute stroke are referred. Our study was performed to analyze collectively the management of stroke in ED-referred elderly patients considering mortality, autonomy outcomes, and factors associated with death at the time of thrombolytics and MRI.

Our findings indicate that management of stroke in elderly patients in the ED is different compared with younger patients, but brings very positive results. Elderly stroke patients seen in the ED were managed with the same delay and received the same treatment as younger patients. Moreover, elderly patients all benefited from a CT scan at the time of the diagnosis, in the same proportion as the younger patients. This result represents important progress compared with previous data that reported a significant decrease of CT scan and antithrombotic treatment use with age (6),(7). However, the explanations for this difference are numerous and could be related to individual practice in various countries, as well as evolution in stroke management. Despite this positive result, some points remain significantly different for elderly patients. At admission, assessment with MRI and admission to the stroke unit were less frequently observed in this group despite a greater severity of stroke in older patients as shown by Rankin-modified scores, ICU referral, and initial mortality. The difference observed for MRI assessment was not explained by MRI contraindication. At discharge from the ED, referral to the neurologic department, particularly to the stroke unit, was significantly lower in elderly patients.

Our results support the fact that despite progress in stroke management, age is still associated with a difference in management using modern methods of brain imaging in patients presenting with stroke in the ED.

However, this age-related difference can be influenced by other factors. Firstly, we found a difference between groups for duration of symptoms, but the nonsignificant difference observed for patients arriving to ED before 3 hours of symptoms duration does not explain a 4-fold less use of MRI and immediate stroke unit referral in the older group. Several studies have shown a beneficial effect of stroke unit or neurologic department management compared with general units for all subgroups of elderly patients (19), (22), but these differences have been inconsistently observed (20). Therefore, this can reflect an individual physician's management without consideration of investigation. Lastly, the hemorrhagic risk of thrombolytic agents in the stroke unit in older patients could contribute to the difference observed in management through its influence on stroke unit admission (23). However, thrombolysis was very rare in our study, and the association between age, thrombolysis, and stroke hemorrhagic transformation is not so clear because some studies did not observe any significant difference between groups according to age (24),(25),(26).

Overall, the age-related differences in management revealed by our study can be explained by several factors. Ageism has been previously reported in the management of cerebrovascular disease for prevention (27), (28), investigation, and treatment (29). However, we cannot affirm that observed differences are related with ageism despite the fact that these differences do not appear to be justified by our results or previous studies in elderly stroke patients.

We found that the modified Rankin score, type of stroke, and dementia were predictors of a 1-year mortality, whereas age was not (21), (30), (31), (32), (33). The results overall highlight the weight of comorbidities compared to age in elderly patients and the need to evaluate and to consider stroke severity more than age, and does not support the notion that age is essentially a negative determining factor in the management of stroke. Previous studies have reported an association of mortality with type of stroke (32),(34),(35),(36), atrial fibrillation (17),(32),(33),(38), diabetes mellitus, increased blood glucose or discontinuous diabetes treatment (31),(33),(37), cognitive impairment (31),(37), living conditions (38), and autonomy (32). In our study, hemorrhagic stroke was associated with mortality, which could have been favored by antithrombotic or anticoagulant treatment (53% of older patients) or falls, a frequent event in this population (39),(40),(41). Previous dementia was independently associated with mortality in stroke patients in our study, as with risk of stroke (42), (43) and severe stroke (38). Both dementia and stroke can share aggravating common factors such as hypertension (44) and apolipoprotein E ?4 (45), (46). However, this association could reflect the patient's frail condition and common shared factors that all contribute to risk of death in stroke patients.

Finally, we observed a higher mortality rate in elderly patients compared to younger patients, but this difference was no longer significant when other significant risk factors were taken into account. This particular finding is markedly different from previous studies, which reported a higher mortality for in-hospital death (15), (19), (21) and 1-year mortality (19), (20), (30) in older patients. Age has been found to be independently associated with greater mortality (21),(30) using multiple logistic regression and survival analyses including initial stroke severity, but one of these studies excluded transient ischemic attacks and cerebral hemorrhage (21) and both used different assessment scales.

Our study has some limitations. This was a comparative study conducted in a single institution, and this might reflect local medical management. In particular, we cannot exclude that different practice patterns reflecting different health care services may have influenced prognosis or outcome of patients. However, with a 250-bed urban hospital including an ED, a MRI, and a stroke unit, our practice can be considered as representative of stroke management in relation to stroke center admission, MRI, and use of thrombolytics.

Because our study was performed in an ED, and patients directly referred to the stroke unit were not considered, most of the stroke patients included within a 3-hour admission and fibrinolysis time window, were probably under-represented in our study because of pre-ED selection for stroke unit admission.

The choice of the modified Rankin score compared with other scales for stroke severity may be criticized but was known to be easily feasible for all physicians in our ED. Its value in our study could reflect co-morbidity consequences together with stroke severity. However, a large majority of our patients were living independently at home, suggesting that the Rankin score mainly reflected stroke severity. Overall, our methods were essentially designed to highlight an association between factors (age and underuse), but not a causative effect. To analyze the effect of age on physician's decision in management and treatment of stroke, a prospective study is needed with consideration for all factors implicated in medical decision making.
In conclusion, our results suggest that comorbidities and disease severity have to be considered more than age for the management of acute stroke in elderly patients. The age-related differences observed in our study highlight the need for new studies dedicated to stroke in elderly patients and its optimal management.

Acknowledgment
I would like to thank Dr Mohammed Hassen Al-Banouby, MD (Consultant and Professor Neurologist, Departments of Neurology and Geriatrics, Ain-Shams University Hospital, Cairo, Egypt) and Dr Mohammed Abdel-Fatah Al-Okl, MD (Consultant and Ass. Professor Geriatrician, Department of Geriatrics Medicine, Ain-Shams University Hospital, Cairo, Egypt) for reviewing the manuscript.
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