ischemic stroke has many causes , clinical presentations , risk factors , courses , and outcomes . management and prognosis of patients with ischemic stroke is directly related to specific mechanisms of the ischemic stroke . in the acute phase of stroke , the most important predictors of outcome are stroke severity [ 2 , 3 ] and patient age .
severe strokes seem to be more frequently caused by cardiac emboli and less frequently by large - artery occlusive mechanisms .
functional status prior to stroke onset , presence of comorbid medical conditions [ 2 , 69 ] , cognitive impairment , and reduced consciousness at onset may also predict a worse prognosis after stroke , although with weaker evidence .
the aim of this study is to estimate the predictors of stroke severity in the acute phase of stroke and to identify the predictors of all - cause long - term mortality subsequent to a first - ever ischemic stroke within a population - based setting . to determine the predictors
is of paramount importance for clinicians to identify patients who are at higher risk for more severe strokes and death .
the cerebrovascular aosta registry ( care ) is a population - based registry recording first - ever strokes in all age groups for a geographically defined area , the aosta valley , italy . the overall study design hasbeen published previously [ 10 , 11 ] .
no selection of patients was performed with regard to age , stroke severity , or comorbid medical conditions before admission .
patients with recurrent stroke , intracerebral or subarachnoid hemorrhage , subdural hematoma , or other causes mimicking stroke ( trauma , infection or an intracranial malignant processes ) were excluded .
hospital care is free , and a very high proportion ( 92.5% ) of stroke patients were admitted to hospital .
the aims of this study were to determine the characteristics of patients who initially presented with ischemic stroke , and to identify predictors of stroke severity and long - term ( all cause ) mortality .
we retrieved medical history prior to the index stroke and the chads2 score   was calculated for all patients .
the following variables were analysed : gender , age ( categorized as < 65 , 6574 , 7584 , and 85 ) , domestic arrangements ( lives with others , alone , or in a community ) , clinical history , and medications . vascular risk factors included history of hypertension , diabetes mellitus , ischemic heart disease ( acute myocardial infarction , angina , or coronary revascularisation ) , low ejection fraction , transient ischemic attack ( tia ) , current or former smoking , hypercholesterolemia , and af , either as a history of af and/or af diagnosed during the index admission with stroke by electrocardiography ( ecg ) and/or 24 hour ecg monitoring . at admission , patients were categorized as treated or nontreated with antithrombotic agents .
patients with af were considered as treated when they were receiving the following treatments : antiplatelet drugs and had chads2 score from 0 to 1 ; warfarin therapy with inr 2.0 to 3.0 at the time of stroke and had chads2 2 .
comorbidity conditions in patients admitted with acute ischemic stroke were scored with the modified charlson index ( ci ) on the basis of hospital discharge icd-9 cm codes   and patient history obtained from standardized case report forms .
a weight was assigned to each indicated diagnosis and each weight was added together to calculate the ci score .
the score varied according to the severity of the disease : myocardial infarction , congestive heart failure , peripheral vascular disease , dementia , chronic pulmonary disease , connective tissue disease , ulcer disease , mild liver disease , and diabetes mellitus were weighted 1 ; diabetes with end - organ damage , moderate to severe renal disease , nonmetastatic solid tumor , leukaemia , lymphoma , and multiple myeloma were weighted 2 ; autoimmune deficiency syndrome and metastatic solid tumor were weighted 6 .
follow - up mri examination or brain ct scan was repeated 2 to 5 days after the index event .
stroke severity was evaluated in the acute phase of the initial stroke by a neurologist certified in the use of the national institute of health stroke scale ( nihss ) .
stroke severity by nihss was categorized as mild ( 04 ) , moderate ( 515 ) , or severe ( 1642 ) .
stroke subtypes were defined using the trial of org 10172 in acute stroke treatment ( toast ) criteria .
metabolic , hematologic parameters and vital signs were recorded in the registry on arrival and again at 2448  h after stroke onset .
the length of hospital stay was defined from the day of admission to a hospital ward to the day of discharge to either his / her own residence to nursing home or to another type of institution .
acute stroke management and secondary prevention in these patient followed current european stroke organization guidelines .
discharged patients were followed up on an annual basis through neurological examination and review of records for further hospitalization .
mortality data were cross - checked with the list of stroke death icd-9 codes registered by the office of legal medicine .
case fatality within 28 days , 1 year , and 5 years was defined as the proportion of cases for which death occurred from stroke onset for all causes .
differences in patient characteristics , premorbid risk factors , and hospital investigations were assessed by  test ( for categorical variables ) or analysis of variance ( for continuous variables ) .
the variables analysed were age , gender , body mass index ( bmi ) , life conditions , prestroke dependency , comorbidities , nihss at admission , vascular risk factors , therapy prior to stroke , pathophysiologic and metabolic factors .
multivariate logistic regression models were used to estimate the impact of possible determinants of stroke severity at admission .
differences between groups and effect of patient characteristics on clinical outcome were assessed using chi - square test .
kaplan - meier survival curves were generated to demonstrate the effect of determinants on long - term survival .
the present analysis focused only on patients with first - ever ischemic stroke , 1057 cases , registered between january 1 , 2004 , and december 31 , 2008 . of these ,
260 patients presented af , of whom 235 ( 90% ) were known to have af and 25 ( 10% ) were diagnosed with af during admission .
the mean age in the af group was 80.8 years ( sd , 10.1 ) , and 74 years ( sd , 13.1 ) in the non - af group ( p < 0.001 ) . at admission , only 27 ( 10.5% ) patients with af were adequately treated according to the current guidelines .
nineteen patients had contraindication to oral anticoagulants because of frequent falls , severe bleeding , and dementia .
as far as stroke severity , multivariate logistic regression analysis identified very old age , female gender , af , low ejection fraction ( < 35% ) , and cardioembolism as independent factors associated with severe stroke ( nihss  16 ) , table 2 .
the mean length of hospital stay for all patients was 15.8 ( 95% ci 14.816.8 ) days .
patients with af had a mean length of stay of 20 days ( 95% ci 17.522.5 ) whereas patients without af had a mean length of stay of 15.3 days ( 95% ci 14.216.4 ) ( p < 0.001 ) . at discharge ,
oral anticoagulants were prescribed to 53% of the af group , 12% of patients did not receive any antithrombotic treatment , whereas antiplatelet agents were given to 35% of the af group as the only antithrombotic treatment and to 88% of the non - af group ( p < 0.0001 ) .
the mean follow - up time was 3.3 years ( 95% ci 3.13.4 ) . during this period , 513 ( 48.5% )
the hazard ratios for 28 day , 1 year , and 5 year mortality were 2.36 ( 95% ci 1.533.63 , p < 0.001 ) , 2.75 ( 95% ci 2.053.68 , p < 0.001 ) , and 2.35 ( 95% ci 1.902.93 , p < 0.001 ) , respectively .
as far as predictors of long - term mortality , the multivariate cox regression analysis showed very old age , prestroke modified rankin scale 35 , charlson index 2 , af , and severe stroke as independent predictors , table 4 . 

figure 1 shows the kaplan - meier curves after ischemic stroke representing the relationship of ( a ) age , ( b ) sex , ( c ) prestroke disability ( evaluated by mrs ) , ( d ) comorbidity ( evaluated by charlson index ) , ( e ) ischemic heart disease , ( f ) atrial fibrillation , ( g ) stroke severity , and ( h ) stroke subtypes with all - cause mortality after ischemic stroke .
in this population - based study , on first - ever ischemic stroke patients , we demonstrated that risk factors such as very old age , af , and cardioembolic stroke have an impact on neurologic impairment as evaluated in the acute phase and on long - term mortality .
the majority of these factors are associated with high risk cardioembolic conditions . in the present study
, very old age was found to be an independent predictor of stroke severity at admission .
there have not been many community - based estimates of gender and older age as significant independent predictors of stroke severity , whereas very old age per se was found to be a strong predictor of outcome and mortality after stroke   and older age of patients with af has been postulated as a major contributing factor for poor prognosis .
female gender has been shown to have more severe strokes than men , as already reported in a previous review .
conversely , our previous results showed that female patients were older and suffered more frequently from af ; hence , female patients generally had a more severe stroke .
we found cardioembolism to be the most common etiology of stroke ( 25.1% ) in our almost exclusively white study population and cardioembolic stroke particularly dominated in the oldest age group .
af - related strokes are expected to increase due to population aging , because it is known the increase of af with age [ 4 , 6 ] . in our study , the mean age of patients with af was older than in other studies [ 2 , 20 ] .
the well - documented impact of af on the prognosis of first - ever ischemic stroke [ 2 , 2022 ] is confirmed in this investigation .
previous studies have reported that stroke patients with af present more often large cortical infarcts , and less frequently lacunar infarction compared with patients without af [ 2 , 3 , 5 ] . this may be explained by the size of cardiac emboli as well as by the lack of collateral vascularization , which may develop and compensate for acute arterial occlusion in patients with gradual occlusion of arteries , such as in atherosclerosis of cervical or cerebral arteries . in this population study , most patients admitted with a stroke who had previously a diagnosis of af were suboptimally anticoagulated before their stroke and only 10% of patients with a history of af were receiving an adequate antithrombotic treatment prior to stroke .
other italian studies on hospital admitted patients have reported underutilization of oral anticoagulant in patients with af [ 23 , 24 ] .
anticoagulation treatment is highly dependent on single patient characteristics such as age , comorbidities , patient 's lifestyle , and feasibility of adequate monitoring of therapy .
the high percentage of nontreated patients is likely attributable to the older age of our population , being anticoagulation treatment difficult to control and to manage .
several factors influenced long - term mortality among which prestroke dependency and comorbidities , more common in the elderly population .
prestroke mrs score 35 and a ci score > 2 were found to be statistically significant independent factors of long - term mortality among first - ever stroke ischemic patients .
many of the identified predictors of long - term mortality have been already reported in previous studies [ 3 , 5 , 18 , 2630 ] but hypertension , diabetes , or smoking .
hyperglycemia at the time of the index stroke was not associated with a worse outcome .
the strength of the present study is due to a community - based design and due to the use of rigorous case ascertainment procedures to enroll all patients with first - ever ischemic stroke .
complete case ascertainment allowed precise estimation of the prevalence of the risk factors among our patients .
however , the limitations of our study must also be recognized : the aosta valley population is predominantly caucasian , which may limit the possibility to generalize our findings to other ethnic groups , in whom the risk of af and other risk factors may differ ; the use of prestroke mrs is not standardized , because the mrs was designed and validated to measure global clinical function after stroke ; our study did not examine the role and impact of hospital treatment practices , given the observational nature of this investigation . in conclusion , the findings of this study suggest that very old age was a major contributing factor for poor prognosis in ischemic stroke patients .
presence of af and cardioembolism were associated with severe stroke and reduced long - term survival . moreover
, long - term mortality after ischemic stroke may be accounted for the presence of prestroke dependency , comorbidity , or at least a history of ischemic heart disease .
 
 background . there is scant population - based information regarding predictors of stroke severity and long - term mortality for first - ever ischemic strokes . 
 the aims of this study were to determine the characteristics of patients who initially presented with first - ever ischemic stroke and to identify predictors of severity and long - term mortality . 
 methods . 
 data were collected from the population - based cerebrovascular aosta registry . between 2004 and 2008 , 
 1057 patients with first - ever ischemic stroke were included . 
 variables analysed included comorbidities , sociodemographic factors , prior - to - stroke risk factors , therapy at admission and pathophysiologic and metabolic factors . 
 multivariate logistic regression models , kaplan - meier estimates , and cox proportional hazards model were used to assess predictors . 
 results . 
 predictors of stroke severity at admission were very old age ( odds ratio [ or ] 2.98 , 95% confidence interval [ ci ] 1.755.06 ) , female gender ( or 1.73 , 95% ci 1.212.40 ) , atrial fibrillation ( or 2.76 , 95% ci 1.724.44 ) , low ejection fraction ( or 2.22 , ci 95% 1.134.32 ) , and cardioembolism ( or 2.0 , 95% ci 1.362.93 ) . 
 predictors of long - term mortality were very old age ( hazard ratio [ hr ] 2.02 , 95% ci 1.652.47 ) , prestroke modified rankin scale 35 ( hr 1.82 ; 95% ci 1.462.26 ) , charlson index 2 ( hr 1.97 ; 95% ci 1.622.42 ) , atrial fibrillation ( hr 1.43 , 95% ci 1.041.98 ) , and stroke severity ( hr 3.54 , 95% ci 2.874.36 ) . conclusions . very old 
 age and cardiac embolism risk factors are the independent predictors of stroke severity . moreover , these factors associated with other comorbid medical conditions influence independently long - term mortality after ischemic stroke . 
1. Introduction
2. Methods
3. Data Analysis
4. Results
5. Discussion