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ORIGINAL ARTICLE
J Res Med Sci 2022,  27:82

One-year survival and prognostic factors for survival among stroke patients: The PROVE-stroke study


1 Nursing and Midwifery Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Isfahan Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
3 Interventional Cardiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
4 The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
5 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran; School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Date of Submission25-Apr-2021
Date of Decision31-May-2022
Date of Acceptance20-Jun-2022
Date of Web Publication25-Nov-2022

Correspondence Address:
Dr. Mohammad Saadatnia
School of Medicine, Isfahan University of Medical Sciences, Hezar Jarib Street, Isfahan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrms.jrms_368_21

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  Abstract 


Background: Survival and prognostic factors following stroke occurrence differ between world regions. Studies investigating stroke features in the Middle-east region are scarce. We aimed to investigate 1-year survival and related prognostic factors of stroke patients in Central Iran. Materials and Methods: It is an observational analytical study conducted on patients registered in the Persian Registry of Cardiovascular Disease-Stroke (PROVE-Stroke) database. Records of 1703 patients admitted during 2015–2016 with the primary diagnosis of stroke in all hospitals of Isfahan, Iran were reviewed. Information regarding sociodemographic characteristics, clinical presentations, medications, and comorbidities were recorded. The living status of patients after 1 year from stroke was considered as 1-year survival. Results: Among 1345 patients with the final diagnosis of stroke, 970 (72.1%) were alive at the 1 year follow-up and the mean survival time based on Kaplan–Meier procedure was estimated 277.33 days. The hemorrhagic and ischemic types of stroke were reported in 201 (15.0%) and 1141 (84.8%) patients, respectively. Age (hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 1.05–1.09), diabetes (HR = 1.49, 95% CI = 1.07–2.06), history of stroke or transient ischemic attack (HR = 1.81, 95% CI = 1.30–2.52), history of warfarin usage (HR = 1.73, 95% CI = 1.11–2.71), hospital complications of hemorrhage (HR = 3.89, 95% CI = 2.07–7.31), sepsis (HR = 1.78, 95% CI = 1.18–2.68), and hydrocephalus (HR = 3.43, 95% CI = 1.34–8.79), and modified Rankin Scale (mRS) ≥3 at the time of hospital dicharge (HR = 1.98, 95% CI = 1.27–3.07), were predictors of 1-year survival. Conclusion: Predictors of 1-year survival can be categorized into unchangeable ones, such as age, diabetes, previous stroke, and mRS. The changeable factors, such as hospital complications of infection and hemorrhage, guide physicians to pay greater attention to reduce the risk of mortality following stroke.

Keywords: Hemorrhagic stroke, Iran, ischemic stroke, prognosis, survival analysis


How to cite this article:
Givi M, Badihian N, Taheri M, Habibabadi RR, Saadatnia M, Sarrafzadegan N. One-year survival and prognostic factors for survival among stroke patients: The PROVE-stroke study. J Res Med Sci 2022;27:82

How to cite this URL:
Givi M, Badihian N, Taheri M, Habibabadi RR, Saadatnia M, Sarrafzadegan N. One-year survival and prognostic factors for survival among stroke patients: The PROVE-stroke study. J Res Med Sci [serial online] 2022 [cited 2023 Feb 3];27:82. Available from: https://www.jmsjournal.net/text.asp?2022/27/1/82/361977




  Introduction Top


Stroke is the second most common cause of disability adjusted life-years, and the second leading cause of mortality in the world. It is reported as the most prevalent neurological disease with a prevalence of 80.1 million cases globally in 2016.[1] Studies suggest an increase in the estimated global lifetime risk of stroke in the recent years.[2] Identifying factors that reduce stroke complications and improve the stroke outcome can increase patients' survival and enhance their quality of life.[3],[4] Accordingly, many studies have investigated positive and negative predictive factors important in the survival of stroke patients. Intermittent claudication, urinary incontinence, and previous history of ischemic attack are some of the independent baseline factors suggested to predict adverse outcomes such as death in 5 years in stroke patients.[5] Another extensive epidemiological study reported stroke type, prestroke index and history of hypertension, ischemic heart disease and diabetes, as the most important predictors of stroke-induced death in a year from hospital admission.[6] There are evidences that these positive and negative predictive factors may differe between world regions considering differences in race, ethnicity, sociodemographic and economic factors, and type of the life style, highlighting the importance of conducting studies on stroke patients in different world regions.[6],[7] Studies investigating factors associated with a faviorable or poor stroke outcome and the stroke features in the Middle east region are scarce. Meanwhile, the incidence rate of stroke has been reported to be 22.7–250 per 100,000 population per year in the middle east, with an increasing trend in the incidence and mortality during the last decades.[8] To the best of our knoweledge, no study has comprehensively investigated different predictive factors among stroke patients in Iran, hitherto. Iran is the second largest country in the Middle East and has an incidence rate of approximately 128–149 stroke cases per 100,000 individuals per year.[3],[9]

The main objective of the present study was to determine 1-year survival rate and different positive and negative predictive factors affecting survival among stroke patients in Central Iran.


  Materials and Methods Top


The present study is an observational study conducted using the information of patients recorded in the Persian Registry of Cardiovascular Disease-Stroke (PROVE-Stroke) database. PROVE is an open-label registry, established in Isfahan province, Iran from 2014 and covers a total population of over 2,000,000 inhabitants. The design and methodology of the PROVE pilot study has been published in detail previously.[10] In brief, records of stroke patients admitted to two hospitals with specialized stroke units, and seven general hospitals in the city of Isfahan were reviewed. Definite diagnosis of acute ischemic or hemorrhagic stroke based on the clinical presentation and computed tomography (CT)/magnetic resonance imaging (MRI) findings was the inclusion criterion in the present study The exclusion criteria were a diagnosis of iatrogenic stroke or transient ischemic attack (TIA), an incomplete medical record regarding the final diagnosis and type of stroke, and lack of informed consent. Information on sociodemographic characteristics, medical history, underlying diseases, history of cigarette/hookah smoking, history of medication usage (before stroke, during hospitalization, and at the time of discharge), laboratory findings, electrocardiogram, echocardiogram, carotid Doppler sonogram, brain CT/MRI findings, and degree of disability using modified Rankin Scale (mRS) were collected. mRS is a well-known scale which is consisted of seven scores (from 0 to 6) that describe the level of patient's disability as recorded by the clinician. Score 0 indicates the absence of any symptoms and score 6 indicates death, while other scores describe various degrees of disability.[11]

Two board certified neurologists classified patients with ischemic type stroke based on their medical records, using the Trial of Org 10172 in Acute Stroke Treatment classification in to five subtypes of large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), stroke of other determined etiology, and stroke of undetermined etiology.[12] Patients with stroke of undetermined etiology were further divided into two groups of those with negative standard evaluations and those with inadequate standard assessments. Patients with hemorrhagic type stroke were classified into two groups of intracerebral hemorrhage and subarachnoid hemorrhage. Living status of patients after 1 year from stroke occurrence was assessed by telephone interview with a first-degree family member of the patient and recorded as 1-year survival. The time of survival during the 1st year was considered as survival time.

The study was approved by the ethics committee of Isfahan University of Medical Sciences.

Statistical analysis

We reported continuous and categorical data as mean ± standard deviation (or median [inter quartile range]) and frequency (percentages), respectively. We compared categorical data using Chi-square or Fisher exact test, where appropriate. We compared continuous data using independent sample t-test or Mann–Whitney U test. Normality assumption was checked using the Kolmogrov–Smirnov test. We used simple proportional hazard cox regression analysis to determine crude hazard ratios (HRs) for 1-year survival of patients. We used multiple cox propportional hazard regression analysis to evaluate the adjusted HRs for 1-year survival of patients using stepwise method (forward selection). The proportional hazard assumptions was checked using Schoenfeld residuals test. We also draw the Kaplan Mayer graph by type of stroke. Statistical analysis was performed using the Statistical Package for the Social Sciences version 25 (SPSS Inc., Chicago, IL, USA) and STATA14 (StataCorp, MP-Parallel Edition, College Station, Texas, USA). P < 0.05 was considered as statistically significant.


  Results Top


Among 1703 patients admitted to the hospital during 2015–2016 with the initial diagnosis of stroke in the primary evaluation, 358 (21.0%) patients were further diagnosed with another medical condition after more comprehensive evaluations and implementing other diagnostic tests. Thus, information regarding 1345 patients with a definite diagnosis of stroke was analyzed in the present study. Survival time for patients was between 0 and 365 days. The mean survival time based on Kaplan–Meier procedure was estimated as 277.33 days (95% confidence interval [CI]: 269.47, 285.20). [Figure 1] presents Kaplan–Meier survival curves by type of the stroke.
Figure 1: Kaplan-Meier survival curves by type of the stroke

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Patients' sociodemographic characteristics, past medical history and drug history before stroke based on the living status on 1-year follow up and type of the stroke could be found in [Table 1]. In general, 710 (52.8%) patients were male and the mean age of patients, regardless of type of the stroke was 69.63 ± 13.81 years. Based on the type of the stroke, the mean age of patients in the hemorrhagic and ischemic groups was 64.85 ± 14.52 and 70.51 ± 13.50 years, respectively. No statistically significant difference was observed in the gender distribution of patients between two hemorrhagic and ischemic groups.
Table 1: Patients' sociodemographic characteristics, past medical history and drug history before stroke based on the living status on 1-year follow up and type of the stroke

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Among 1345 patients with the final diagnosis of stroke, 970 (72.1%) were alive at the 1-year follow-up. The mean age of patients who died from stroke was significantly higher than the mean age of patients who survived the condition (75.14 [12.61] and 67.50 [13.67] years, respectively [P < 0.001]). No statistically significant differences were observed between the proportion of males and females among dead and alive patients (P = 0.18).

As shown in [Table 1], 17% of all patients reported the history of cigarette or hookah smoking and 8.8% reported history of drug abuse. Previous history of stroke was the only underlying condition that was statistically significantly different between alive and dead patients (18.6% compared to 26.1% for alive and dead patients, respectively [P = 0.002]). Hypertension (66.4%) and diabetes (33.1%) were the most reported underlying diseases among all patients.

[Table 2] represents patients' clinical presentations, hospital complications, and drug history during hospitalization and after hospital discharge based on the living status on the 1-year follow-up and type of the stroke. The mean duration of hospitalization was significantly higher in those who expired following stroke compared to patients who survived the condition (P < 0.001). The duration of hospitalization was also higher in patients with hemorrhagic type stroke compared to those with ischemic stroke (P < 0.001) [Table 2].
Table 2: Patients' clinical presentations, hospital complications, and drug history during hospitalization and after hospital discharge based on the living status on 1-year follow up and type of the stroke

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Regarding the type of the stroke, 201 (15%) patients had hemorrhagic type, with intracerebral hemorrhage in 177 (88.1%) and subarachnoid hemorrhage in 24 (11.9%) patients. The most reported underlying condition among patients with intracerebral and subarachnoid hemorrhages were hypertension (75.6%) and aneurysm (27%), respectively. Ischemic type stroke was diagnosed in 1141 (84.8%) patients. SVO was present in 281 (24.6%) patients, CE in 230 (20.1%) patients, and LAA in 89 (7.8%) patients. Stroke of other determined etiology and stroke of undetermined etiology were responsible for 21 (1.8%) and 520 (45.76%) cases, respectively. Type of the stroke was not reported in 3 (0.2%) patients. Patients' risk factors, clinical presentations, and mRS at the time of hospital discharge among patients with ischemic stroke could be found in [Supplementary File Table 1]. Furthermore, the effects of subtypes on patients' survival among ischemic stroke patients are tabulated as [Supplementary File Table 2].



As could be seen in [Table 2], evaluating hospital complications revealed that infectious complications (pneumonia, sepsis, and urinary tract infection), hydrocephalus, and hemorrhagic transformation were statistically significantly higher in patients who further died from stroke compared to those who survived the condition (P < 0.001 for all). Cerebral edema was also more common among dead patients (P = 0.023). Furthermore, stroke presenting symptoms were significantly different among dead and alive patients and those with hemorrhagic or ischemic type strokes. Lack of consciousness was more common in patients who died following stroke compared to alive patients (P < 0.001). While alive patients compared to those who were dead a year following stroke happening, showed more symptoms of hemiparesis (P = 0.042), aphasia (P = 0.012), dysarthria (P < 0.001), diplopia (P = 0.027), dizziness (P < 0.001), imbalance (P = 0.003), and headache (P = 0.004).

Number of cases that were using warfarin and statins before stroke occurrence was significantly different among dead and alive patients (P < 0.001 and P = 0.038 for warfarin and statin use, respectively) [Table 2]. Overall, antihypertensives, aspirin, and oral hypoglycemic agents were the most prevalent drugs patients reported to use before stroke onset. The prescription of aspirin, clopidogrel, and statins during hospitalization was significantly higher for patients who were alive after 1 year from stroke happening compared to dead patients (P ≤ 0.001).

During hospitalization, 199 (14.79%) patients died from stroke or related hospital complications. Furthermore, during 1st year after stroke, 176 patients died. Results from mRS revealed that almost 84% of the patients who died during 1st year after hospital admission, were discharged from hospital with mRS score ≥3. Considering type of the stroke, mRS scores were significantly higher among patients with hemorrhagic type stroke compared to patients with ischemic type stroke, and most of the ischemic stroke patients were discharged from hospital with mRS score ≤3 [Table 3].
Table 3: Degree of disability using modified Rankin Scale at the time of hospital discharge based on the living status in a year from stroke and type of the stroke

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Results from the simple Cox regression analysis is found in [Supplementary File Table 3]. The factors identified to be effective based on the simple Cox regression analysis were used to perfrom multiple cox regression analysis. As could be seen in [Table 4], the predictive variables of death in a year from stroke occurance were age (HR = 1.07, 95% CI = 1.05–1.09), diabetes (HR = 1.49, 95% CI = 1.07–2.06), history of stroke or TIA (HR = 1.81, 95% CI = 1.30–2.52), history of warfarin usage (HR = 1.73, 95% CI = 1.11–2.71), hospital complications of hemorrhage (HR = 3.89, 95%CI = 2.07–7.31), sepsis (HR = 1.78, 95% CI = 1.18–2.68), and hydrocephalus (HR = 3.43, 95% CI = 1.34–8.79), and mRS ≥ 3 compared to ≤ 2 at the time of hospital dicharge (HR = 1.98, 95% CI = 1.27–3.07).
Table 4: Adjusted hazard ratio (95% confidence interval) to predict patients's 1 year survival

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  Discussion Top


In the present study, examination of the profiles of 1345 stroke patients from the PROVE-Stroke database showed that by a year from stroke occurence, 375 (27.9%) patients were died. Age but not gender was a mortality predictor and the mean age of dead patients was higher than those who survived the cindition. The presence of diabetes, history of stroke or TIA, using warfarin before hospitalization, hospital complications of hemorrhage, sepsis, and hydrocephalus, and mRS ≥3 compared to ≤2 at the time of hospital dicharge were identified as mortality predictors. History of hypetension and hyperlipidemia were similar among dead and alive patients.

The factors affecting recovery and survival of stroke patients are of great importance and not completely understood yet.[13],[14] Here, we found a survival rate of 72.1% on 1-year follow-up among patients with the final diagnosis of stroke. In the Nanjing stroke registry, 1-year survival rate of Chinese patients with a first time stroke was reported to be 86.4%.[15] In another study in Brazil evaluating 75,000 patients with stroke, 69% were reported to be alive in a year from stroke occurance.[16] Differences between stroke survival rates reported in our study and others are suggested to be mainly due to the different sociodemographic characteristics of the patients, as well as patients' past medical histories. Age has been reported to be an imprtant factor in determining the chance of mortality in stroke patients.[15] It is suggested that the mortality rate increases among older patients due to the poor physical ability to compensate the lesion and less social support in them.[17] One study reported more than three times higher risk of death among patients over 65 years compared to younger patients.[18] Another study showed that those over 75 years would face death five times more than other stroke patients.[15]

In the present study, there was no statistically significant differences in the survival rate between men and women. Results from the Dijon stroke registry on stroke survival also showed no difference between genders,[19] although there are studies suggesting the survival following stroke may be affected by the patient's sex.[20] Extensive registry-based studies have reported that some factors including adherence to the treatment after hospital discharge and factors affecting rehabilitation were more responsible for different survival rates observed between genders in these studies.[21],[22]

Regarding the type of the stroke, in the present study, 201 (14.94%) patients were diagnosed with hemorrhagic type and 1141 (84.83%) patients with ischemic type strokes. Patients with hemorhagic type stroke showed higher hazard of mortality compared to the ischemic stroke patients. In a study conducted in Denmark on 40,000 stroke patients, 10% were diagnosed with hemorrhagic type and 90% with the ischemic type strokes. The authors reported that the likelihood of death among patients with hemorrhagic type stroke was 1.56 times higher than the other type.[23] In another study, 1-month mortality rate of patients with hemorrhagic type stroke was reported to be about 70.8%, which is considerably high.[15] Hence, it can be concluded that although the percentage of patients with hemorrhagic type stroke is lower than those with ischemic type stroke, their mortality rate is higher. This can be due to the higher prevalence of some risk factrors such as hypertension, aneurysm, and alcohol consumption in the hemorrhagic type stroke patients, which can lead to severe brain damages.[24] Furthermore, we found longer mean duration of hospitalization in these patients compared to the individuals with ischemic type stroke. The longer duration of hospitalization in patients with hemorrhagic type stroke substantially indicates worse condition of them at the time of hospital admission, as well as higher hospital complications among them which both increase the chance of mortality.

The presence of specific underlying diseases including diabetes, and previous history of stroke or TIA as the predictors of mortality was the other finding of the current study. In a study on chines patients, diabetes, smoking, and previous history of stroke were found to be associated with the increased risk of death after a first-ever stroke.[15] Furthermore, a previous study in Iran showed that diabetes, smoking, history of previous stroke, and myocardial infarction were all the predictors of mortality in stroke patients.[25] The increased risk of stroke mortality observed in diabetic patients may be due to the microvascular complications of diabetes, which can cause fibrinoid necrosis and subcortical myocardial infarction.[24] On the other hand, although the history of high blood pressure/hypertension and dyslipidemia are suggested to be associated with reduced survival of stroke patients, we found no relationships in our study.[15],[25] This could be due to the differences in the definition of high blood pressure and abnormal lipid profile among studies, as well as patients' recall bias.

Among the controlable factors found to increase hazard of mortality, we found that the hospital complications of hemorrhage, sepsis, and hydrocephalus had the highest HR. It emphasizes the importance of proper management of stroke patients during hospitalization. Another population-based study in Denmark also reported the relationship between hospital complications, especially pneumonia and increased risk of mortality and length of hospitalization among stroke patients.[26]

Another important finding of the present study is the effect of patiens' drug histories on their survival. We found higher prevalence of warfarin usage and lower prevalence of statin usage among dead patients compared to the patients who were alive 1 year poststroke. No significant differences were observed regarding other types of used medications between dead and alive patients. These findings are in the same vein with findings from other studies that reported higher risk of mortality among stroke patients using warfarin.[27] The reduced rate of mortality observed with statin usage among our patients could be due to the specific functions these medications impose. Statins have been widely used to reduce cardiovascular accidents and stroke complications. These medications, not only directly affect the level of cholestrol, also reduce the risk of atherosclerosis due to their anti-inflammatory effects and have plaque stabilizing effects.[28],[29]

There are some limitations to the present study; first, as these patients were recruited from 9 hospitals in the city of Isfahan, differences in medical examinations and imaging studies present which may affect the results. Second, we reviewed patients' medical records retrospectively and some biases may happen in the retrospective evaluation of patients records. Third, we should note the possibility of patients' recall biases regarding their past medical histories, which was inevitable.


  Conclusion Top


Here we reported the 1-year survival and mean survival time of patients with stroke, based on PROVE-Stroke, which can help researchers and clinicians predict the outcome of Iranian patients following stroke. Comparing the statistics with the global reports shows that the stroke features and survival following stroke in the present study were not much different from the other world regions. Studying the predictors of 1-year survival showed two distinct factors; changeable and unchangeable. The unchangeable ones, such as age, diabetes, previous stroke, and mRS, show which factors the physician should consider more precisely in the medical history of patients for more intense treatment and closer follow-up. The changeable factors, such as hospital complications of infection and hemorrhage, can guide physicians to the factors that require greater attention for more appropriate treatment to reduce these complications and the risk of mortality following stroke. According to the results of the present study, we recommend to implement screening programs for identifying the factors that can increase the risk of mortality in patients following stroke.

Availability of data and material

The data that support the findings of this study are available on request from the corresponding authors upon reasonable request. The data are not publicly available due to privacy and ethical restrictions.

Acknowledgments

The authors of this study are very grateful to the members of the PROVE team and the staff of the Isfahan Cardiology Research Institute for their assistance and cooperation.

Financial support and sponsorship

The project was funded by the deputy director of research and technology, the Isfahan Cardiovascular Research Institute (project registration number: 296017).

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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