Ischemic Strokes in Pakistan: Observations from the National Acute Ischemic Stroke Database Bhojo A. Khealani, FCPS,* Maria Khan, FCPS,* Muhammad Tariq, FRCP,† Abdul Malik, MD,‡ Alam I. Siddiqi, FCPS,x Safia Awan, MSc,* and Mohammad Wasay, MD, FRCP, FAAN*

Background: The objective of this study was to establish a multicenter ischemic stroke registry, first of its kind in Pakistan, to provide insight into the epidemiology, subtypes, and risk factors of ischemic strokes in this country. Methods: Four academic centers (3 urban and 1 rural) participated in this project. The inclusion criteria for subjects included adults (.14 years) with acute neurologic deficit, consistent with clinical diagnosis of ischemic stroke and supported by neuroimaging. Results: Data were available for 874 subjects. Mean age of the subjects was 59.7 years, 60.5% were males, and 18% were young. Large vessel strokes were the most common subtype found in 31.7% subjects, followed by small vessel disease (25.7%) and cardioembolic strokes (10.4%). Almost 32% subjects had ill-defined etiology for their ischemic stroke. Dyslipidemia was a most common risk factor present in 83% patients. Data related to in-hospital complications were available for 808 subjects, of which 233 complications were recorded. Pneumonia was the most common of these seen in 105 (13%) subjects, followed by urinary tract infection (7.2%). Outcome at discharge was recorded for 697 subjects. Ninety-two had died during their hospital stay (13.2%). Only 36% subjects had a favorable outcome at discharge defined as a modified Rankin Scale (mRS) score of 2 or less. A total of 446 of 697 subjects had poor outcome at discharge (defined as an mRS score $3). Conclusions: Hypertension and dyslipidemia were the most common risk factors and large vessel atherosclerosis was the most common stroke etiology. Elderly patients were significantly more likely to have in-hospital complications, die during their hospital stay, and have a higher mRS score at discharge. Key Words: Stroke—Pakistan—ischemic— south Asia—outcome. Ó 2014 by National Stroke Association

From the *Department of Neurology (Medicine), Aga Khan University, Karachi; †Pakistan Institute of Medical Sciences, Islamabad; ‡Liaquat National Hospital, Karachi; and xShaheed Benazir Bhutto Medical University, Larkana, Pakistan. Received December 16, 2013; revision received January 3, 2014; accepted January 9, 2014. Funding for this study was provided by a seed money grant from Aga Khan University. Authors report no conflict of interest. Address correspondence to Mohammad Wasay, MD, FRCP, FAAN, Department of Neurology, Aga Khan University, Stadium Road, Karachi 74800, Pakistan. E-mail: mohammad.wasay@aku. edu; [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.01.009

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Introduction Stroke is the leading cause of disability and the second leading cause of mortality in the world today.1,2 Substantial variation exists in the distribution of global burden of stroke. In the years to come, the incidence of this devastating condition is expected to decrease in high-income countries, whereas it is expected to double in low- and middle-income countries.3 Pakistan is no exception to this. The true burden of stroke is unknown in our part of the world. A recent community-based study conducted in a periurban settlement of Karachi demonstrates the abundance of vascular risk factors in this region4 with

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alarmingly high rates of tobacco use, abdominal obesity, hypertension, and diabetes. Judging by the prevalence of risk factors, one can expect the burden of cardiovascular diseases, including stroke to be high.5 Ischemic stroke is the predominant stroke subtype, and although its incidence has decreased in high-income countries because of better preventive strategies, it is increasing in less developed countries primarily because of increased longevity, changes in lifestyle factors, and inadequate preventive strategies.6 To capture all new strokes occurring in the country, there is a need to set up a proper stroke surveillance system. World Health Organization suggests a 3-step approach to stroke surveillance in a well-defined community.7 The first and most important step in this is a hospital-based stroke registry. Because of a lack of proper health infrastructure, such registries are virtually nonexistent in this country. The published work on stroke epidemiology is also limited to single center series, reviews, and editorials,8,9 which does not give an adequate idea of the overall picture the condition presents with. Therefore, our group set out to establish the first-ever multicenter ischemic stroke registry to have a more representative group of patients for understanding stroke in this country. No previous studies have enrolled patients from rural areas. In view of the paucity of good quality data on ischemic strokes from Pakistan, the objective of this study was to establish a multicenter ischemic stroke registry, first of its kind in Pakistan, to provide insight into the epidemiology, subtypes, and risk factors of ischemic strokes in this country.

Methods This National Acute Ischemic Stroke Databank was established as a first multicenter effort in Pakistan to come up with a reliable stroke database. Four academic centers from 2 large cities (2 from Karachi and 1 from Islamabad) and 1 from rural area (Larkana) participated in this project. All 4 hospitals have well-established acute neurology services with trained neurologists and imaging facilities. The inclusion criteria for subjects included adults (.14 years) with acute neurologic deficit, consistent with clinical diagnosis of ischemic stroke and supported by neuroimaging (computerized tomography [CT] or magnetic resonance imaging [MRI]). Those with intracranial hemorrhage or other causes of neurologic deficit were excluded from this study. All subjects who presented to the study centers with acute stroke between January 1, 2007 and December 31, 2007 were evaluated by trained neurologists to confirm the diagnosis. For those willing to participate, a written informed consent was taken either from the subject or their surrogate. Thereafter, a structured questionnaire was filled out by data collecting officers who recorded information on demographics, stroke severity (measured using National Institutes of

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Table 1. Known risk factors (n 5 874) Hypertension Diabetes Dyslipidemia Ischemic heart disease Atrial fibrillation Smoker Pack years Previous stroke Family history of stroke

444 (50.8) 227 (26) 204 (23.3) 135 (16.7) 17 (2.1) 154/717 (17.6) 28.07 (14.57) (Range 1-60) 161 (18.4) 68/833 (7.8)

Health Stroke Scale [NIHSS]10 and modified Rankin Scale [mRS]11), vascular risk factors, stroke workup, and stroke subtype (using TOAST [Trial of org10172 in acute stroke treatment] criteria12). For risk factors, the following definitions were used. A diagnosis of hypertension was made if the patient’s blood pressure surpassed 140 (systolic) and/or 90 (diastolic) (millimeters of mercury) on repeated measurements during hospitalization or physical evaluation, or if the patient was being treated with antihypertensive drugs at the time of admission. A diagnosis of diabetes mellitus was based on self-report, fasting serum glucose level of 120 mg/dL or more, or if the patient was being treated with insulin or hypoglycemic drugs. Dyslipidemia was defined as a fasting serum total cholesterol of 200 mg/dL or more, a serum low-density lipid of 100 mg/dL or more, and/or a serum high-density lipid of 40 mg/dL or less. History of cigarette smoking was positive if the patient had smoked 10 or more cigarettes daily for more than 10 years. Atrial fibrillation was evaluated on an electrocardiogram (ECG), carotid stenosis on Carotid Doppler ultrasound, and left ventricular (LV) dysfunction on an echocardiogram. Severe LV dysfunction was defined as an ejection fraction of 30% or less. All data were coded to maintain confidentiality and centralized at the Aga Khan University Hospital. Ischemic strokes were classified according to the TOAST criteria into the following 5 categories: large artery atherosclerosis (LAA), small vessel occlusion, cardioembolism, other determined cause, and undetermined cause. One study neurologist at the center assigned each stroke to 1 of these categories based on risk factor profiles, clinical

Table 2. Dyslipidemia among stroke patients HDL ,40 (419) HDL ,35 (419) LDL .100 (458) Total cholesterol .200 (450) Dyslipidemia (cholesterol .200, or LDL .100, or HDL ,40) (443)

233 (55.6) 151 (36.0) 284 (32.5) 122 (14) 368 (83.1)

Abbreviations: HDL, high-density lipid; LDL, low-density lipid. Total number of subjects tested are in parenthesis.

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Table 3. In-hospital complications (n 5 808) Complication

N (%)

Pneumonia UTI GI bleed Stroke/TIA MI/angina CCF/cardiogenic shock DVT Phlebitis

105 (13.0) 58 (7.2) 13 (1.6) 8 (1.0) 14 (1.7) 28 (3.5) 3 (.4) 4 (.5)

Abbreviations: CCF, congestive cardiac failure; DVT, deep vein thrombosis; GI, gastrointestinal; MI, myocardial infarction; TIA, transient ischemic attack; UTI, urinary tract infection.

presentation, and stroke workup. The workup included echocardiogram, Carotid Doppler ultrasound, brain imaging (CT or MRI), and blood workup for diabetes dyslipidemia and hypercoagulability.

Data entry and analysis were performed on SPSS version 19.0 (SPSS Inc., Chicago, IL). For continuous variables, means along with standard deviations and for categorical data, frequencies and percentages are reported. For gender comparison, the chi-square test of independence was used for categorical variables and the student t test for continuous variables. Binary logistic regression was used to compare the predictors of poor outcome (mRS score $3) and in-hospital death among elderly patients (age $ 70 years). A P value of .05 was considered statistically significant. Study was approved by Ethics Review Committee of all participating centers.

Results Data were available for 874 subjects from 4 hospitals. The Aga Khan University Hospital contributed the largest number of subjects (58%), followed by Pakistan Institute

Table 4. Gender comparison Variables

Male n 5 529

Female n 5 345

Age mean (SD) Systolic BP mean (SD) Diastolic BP mean (SD) RBS mean (SD) Less than 45 n (%) TOAST Large vessel Small vessel Cardioembolic Unknown etiology Risk factors DM (RBS . 200) HTN Dyslipidemia Smoker Carotid stenosis .70% A-fib on ECG Severe LV dysfunction Investigations MRI Echocardiography ECG Carotid Doppler Complications Pneumonia UTI Stroke severity NIHSS .14 mRS at discharge 0-2 3-5 6 Hospital stay mean (SD)

59.21 (13.76) 146.88 (30.37) 86.24 (17.75) 168.13 (87.13) 440 (83.2)

59.36 (14.27) 152.93 (31.74) 88.17 (18.0) 169.83 (83.38) 281 (81.4)

P value .88 .006 .12 .79 .52

164 (31) 143 (27) 49 (9.3) 173 (32.7)

113 (32.8) 82 (23.8) 42 (12.2) 108 (31.3)

.40

98 (27.1) 199 (40.9) 236 (85.8) 135 (33.2) 19 (10.9) 20 (4.6) 25 (9.4)

74 (28.0) 159 (49.4) 132 (78.6) 12 (5.1) 5 (4.9) 23 (7.8) 9 (5.1)

.81 .02 .048 ,.001 .14 .07 .049

137 (30.3) 273 (56.2) 474 (89.6) 250 (47.3)

81 (26.7) 186 (57.8) 315 (91.3) 129 (37.4)

.29 .66 .48 .004

63 (13.0) 27 (5.6) 156 (33.8)

42 (13.0) 31 (9.6) 110 (36.5)

.97 .03 .06

166 (37.8) 218 (49.7) 55 (12.5) 5.93 (5.12)

89 (30.9) 162 (56.3) 37 (12.8) 5.94 (5.25)

.14

.99

Abbreviations: A-fib, atrial fibrillation; BP, blood pressure; DM, diabetes mellitus; ECG, electrocardiogram; HTN, hypertension; LV, left ventricular; MRI, magnetic resonance imaging; mRS, modified Rankin scale; NIHSS, National Institutes of Health Stroke Scale; RBS, random blood sugar; SD, standard deviation; UTI, urinary tract infection.

STROKE IN PAKISTAN

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Table 5. Stroke in young

Male n (%) Systolic BP mean (SD) Diastolic BP mean (SD) RBS mean (SD) TOAST Large vessel Small vessel Cardioembolic Unknown/other defined Stroke severity NIHSS Risk factors DM HTN Current smoker IHD Previous stroke A-fib on ECG Investigations MRI/CT Echocardiography ECG Carotid Doppler In-hospital complications Pneumonia UTI GI bleed MI/angina mRS at discharge 0-2 3-6 Hospital stay

,45 y, n 5 153

.45 y, n 5 721

P value

89 (58.2) 134.6 (28.4) 84.1 (17.2) 143.8 (49.1)

440 (61) 150.3 (30.9) 86.7 (17.4) 170.8 (91.0)

.52 ,.001 .20 ,.001

47 (30.7) 22 (14.4) 24 (15.7) 60 (39.2) 12. (8.7)

230 (31.9) 203 (28.2) 67 (9.3) 221 (30.7) 12.7 (9.4)

.001

.89

8 (8.6) 35 (37.6) 17 (18.3) 7 (7.5) 6 (6.5) 4 (4.3)

90 (18.0) 230 (45.9) 72 (14.4) 93 (18.6) 101 (20.2) 31 (6.2)

,.025 .14 .33 .01 .002 .48

90 (96.8) 63 (67.7) 86 (92.5) 42 (45.2)

485 (96.8) 309 (61.9) 462 (92.2) 231 (46.2)

.99 .29 .93 .85

10 (10.8) 3 (3.2) 1 (1.1) 0 (.0)

77 (15.4) 27 (5.4) 10 (2.0) 12 (2.4)

.25 .38 .55 .13

42 (34.1) 81 (65.8) 6.1 (4.4)

213 (35.3) 391 (64.8) 5.1 (4.4)

.75 .60

Abbreviations: A-fib, atrial fibrillation; BP, blood pressure; CT, computed tomography; DM, diabetes mellitus; ECG, electrocardiogram; GI, gastrointestinal; IHD, ischemic heart disease; MI, myocardial infarction; MRI, magnetic resonance imaging; mRS, modified Rankin scale; RBS, random blood sugar; SD, standard deviation; UTI, urinary tract infection.

of Medical Sciences (Islamabad) (25%), Liaquat National Hospital (10%), and Shaheed Benazir Bhutto University, Larkana (7%). The mean age of the subjects was 59.7 years, 60.5% were males, 18% were young (,45 years), and 19% were elderly (.70 years). Risk factors reported at admission are provided in Table 1. When classified according to the TOAST criteria, large vessel strokes were the most common subtype found in 31.7% subjects. This was followed by small vessel disease (25.7%) and cardioembolic strokes (10.4%). Almost 32% subjects had ill-defined etiology for their ischemic stroke. Imaging data were available for 862 subjects. Of these 602 (69%) underwent CT scans and the rest had MRIs. Three quarters of the strokes were in the anterior circulation of which most were parietal lobe infarctions. Brain stem infarcts were seen in 14%. Old infarcts were present in 33% scans. Magnetic resonance angiogram was done in

less than 200 patients, of which 42% showed diffuse or focal stenosis of a major intracranial vessel. Stroke severity as per NIHSS was recorded for 763 subjects. Of these 266 (34.9%) subjects had severe strokes defined as NIHSS score of 14 or more. Dyslipidemia was the most common risk factor present in 83% patients. A detailed description of lipid abnormalities is provided in Table 2. ECG was available for 731 subjects, of which 299 abnormalities were reported. The most common abnormality was LV hypertrophy (13.5%), followed by ischemia (10.5%). Atrial fibrillation was found on an ECG in 5.9% subjects. Echocardiography was carried out on 507 subjects. Of these 35 (6%) subjects had severe LV dysfunction defined as an ejection fraction of less than 35%. LV diastolic dysfunction was the most common reported abnormality seen in 193 subjects. Among defined cardioembolic sources for ischemic stroke, 18 subjects had LV clot, 2 had right ventricular clot, 3 had patent foramen ovale, and 1 had an atrial septal defect.

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Table 6. Stroke in elderly

Male n (%) Systolic BP mean (SD) Diastolic BP mean (SD) RBS mean (SD) TOAST Large vessel Small vessel Cardioembolic Unknown etiology Risk factors DM (RBS .200) HTN Dyslipidemia Smoker Carotid stenosis.70% A-fib on ECG Severe LV dysfunction Investigations MRI Echocardiography ECG Carotid Doppler Complications Pneumonia UTI Stroke severity NIHSS .14 mRS at discharge 0-2 3-5 6 Hospital stay mean (SD)

,70 y, n 5 711

.70 y, n 5 163

P value

436 (61.3) 149.0 (31.13) 87.9 (18.2) 169.4 (86.8)

93 (57.1) 146.9 (29.2) 83.4 (16.1) 153.1 (67.9)

.32 .45 .006 .06

230 (32.3) 177 (24.9) 73 (10.3) 231 (32.5)

47 (28.8) 48 (29.4) 18 (11) 50 (30.7)

.59

146 (28.6) 286 (43.8) 292 (84.6) 127 (24.5) 20 (8.8) 31 (5.2) 27 (7.7)

26 (22.6) 72 (46.5) 76 (77.6) 20 (16.3) 4 (7.8) 12 (9.0) 7 (7.6)

.19 .55 .10 .14 .82 .09 .98

186 (27.1) 405 (57) 648 (91.1) 312 (43.9)

52 (34) 102 (62.6) 141 (86.5) 64 (41.1)

.09 .21 .79 .54

72 (11.0) 40 (6.1) 211 (33.9)

33 (21.3) 18 (11.6) 55 (39.0)

.001 .02 .38

220 (38.6) 285 (50.0) 65 (11.4) 5.97 (5.42)

31 (24.4) 69 (54.3) 27 (21.3) 5.80 (3.98)

.001

.74

Abbreviations: BP, blood pressure; DM, diabetes mellitus; ECG, electrocardiogram; LV, left ventricular; MRI, magnetic resonance imaging; mRS, modified Rankin scale; NIHSS, National Institutes of Health Stroke Scale; RBS, random blood sugar; SD, standard deviation; UTI, urinary tract infection.

LV wall motion abnormalities were present in 114 (23%) subjects. Carotid ultrasound was carried out in 277 subjects, of whom 24 (8.7%) had stenosis of greater than 70% on the symptomatic side. Data related to in-hospital complications were available for 808 subjects, of which 233 complications were recorded. Pneumonia was the most common of these, seen in 105 (13%) subjects, followed by urinary tract infection (7.2%). Table 3 lists the various in-hospital complications observed in these ischemic stroke patients. Average hospital stay for subjects was 5.93 days (standard deviation, 5.147). Outcome at discharge was recorded for 697 subjects. Ninety-two had died during their hospital stay (13.2%). Only 36% subjects had a favorable outcome at discharge defined as an mRS score of 2 or less. List of discharge medication was only available for 625 patients. More than 87% patients were discharged on antiplatelets, 10% were discharged on anticoagulation with warfarin, 53% on statins, 31% on antihypertensive

medications, and 16% on insulin or oral hypoglycemic agents. Gender comparison revealed a significantly higher proportion of hypertension, dyslipidemia, smoking, and severe LV dysfunction among men compared with women. However, there were no differences in stroke subtypes, stroke severity, and outcomes at discharge between the 2 genders (Table 4). Young stroke patients (,45 years) were more likely to have cardioembolic stroke compared with older population. A comparison of these groups (,45 versus .45 years) is provided in Table 5. More than 19% patients in our database were elderly (.70-years old). These elderly patients were more likely to develop in-hospital complications including pneumonia and urinary tract infection and had higher mortality (Table 6). A total of 446 of 697 subjects had poor outcome at discharge (defined as an mRS score $3). Poor outcomes

STROKE IN PAKISTAN

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Table 7. Risk estimates for poor outcome at discharge (mRS score .3 and in-hospital death) for those aged more than 70 years compared with those aged less than 70 years (628 included in analysis) Odds ratio (95% confidence interval) Poor outcome (mRS score .3) Model 1 Model 2 Model 3 In-hospital death Model 1 Model 2 Model 3

1.92 (1.24-2.98) 1.75 (1.08-2.84) 1.52 (.92-2.51) 2.47 (1.43-4.27) 2.13 (1.28-3.56) 2.08 (1.16-3.75)

Model 1: adjusted for gender. Model 2: adjusted for gender, hypertension, and TOAST. Model 3: adjusted for gender, hypertension, TOAST, pneumonia, and UTI.

were seen more in those aged more than 70 years (75.6% versus 61.4% in those ,70 years). The odds of poor outcome at discharge were 2.0 times in the elderly compared with those aged less than 70 years. This difference, however, was completely attenuated when adjusted for potential confounders like gender, hypertension, stroke subtype, and complications as seen in Table 7. When in-hospital death alone was considered, the risk estimates remained significant after adjusting for significant potential confounders.

Discussion In this unselected sample of 874 subjects with ischemic strokes, 60% were men, and 19% were aged more than 70 years. Hypertension and dyslipidemia were the most common risk factors, and large vessel atherosclerosis was the most common stroke etiology. Almost one fifth of the subjects had suffered from a previous stroke, indicating deficiencies in secondary stroke prevention strategies for these patients. Elderly patients were significantly more likely to have in-hospital complications, die during

their hospital stay, and have a higher mRS score at discharge. To the best of our knowledge, this is the first multicenter ischemic stroke series from Pakistan. A number of single center case series have been published over the past decades but their generalizability has been limited.13 Also this is the largest single study of ischemic stroke patients from this country. The mean age of stroke patients in our study was low compared with the patients from Italy (71 years), America (68 years), India (63 years), and China (60 years). A recent hospital-based study from Pakistan showed that the mean age of patients with intracerebral hemorrhage was 56 years and it decreased 5 years during the last 10 years.14 The number of young stroke patients is high compared with western countries but similar to studies reported from India and China. We found hypertension and dyslipidemia to be the most common risk factors in our patient population. This is consistent with the previous studies15-20; however, the proportions have been somewhat different. Self-reported hypertension in our study was 44.3%, whereas previous studies have reported higher percentages in the range of 50%-86%.15,17,18,19,21 This might be because of the variability in defining hypertension, we only considered self-reporting because blood pressure changes after acute stroke are not truly reflective of a hypertensive state. Similarly, we found dyslipidemia in 83% of the subjects tested, whereas the proportions have been much lower in previous single center studies. Again the reason may be variability in defining dyslipidemia. Basharat et al18 report dyslipidemia in 59.1% of the 281 subjects, and this was the highest reported figure so far from this region. They included low levels of high-density lipids also in the definition of dyslipidemia similar to our case. This can explain the higher percentages seen in these 2 studies. Stroke registries from other regional countries, namely India and Taiwan, also show a similar prevalence of vascular risk factors, with hypertension, smoking, dyslipidemia, and diabetes being the main culprits.22,23 In the Khorasan stroke registry, hypertension and previous history of stroke were the most frequent risk factors.24

Table 8. Relative proportions (%) of ischemic stroke subtypes from selected registries in India and Pakistan

Author and year

Sample size

Large artery atherosclerosis (% of total)

Kaul et al26 2002 Razzaq et al23 2002 Syed et al14 2003 Deleu et al24 2006 Aquil et al16 2011 Sher et al25 2013

392 118 (15-45 y) 393 303 (32% South Asians) 100 75 (15-45 y)

41 22 26.9 10 31 20

Small vessel disease (% of total) 18 42.7 83 43 16

Cardioembolism (% of total) 10 11 6.1 8 25.3

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Carotid stenosis as a risk factor for ischemic stroke has also not received much attention in previous studies. A few studies have reported the proportion of stroke subjects with stenosis but the definition of carotid stenosis in these studies is not clear. Therefore, the percentages are as high as 39% 25 or higher mentioned in some local journals. In our subjects, only a stenosis of greater than 70% was considered as significant and found in only 8.7% subjects evaluated for it. A recent study of 672 stroke patients showed evidence of high-grade stenosis (70%99%) in 12% patients.26 Workup for intracranial atherosclerosis was done (by magnetic resonance angiography) in limited number of patients, of which 42% had diffuse or focal stenosis of a major intracranial vessel. This finding is in agreement with the reports demonstrating high frequency of intracranial disease in Asian population. This is the first large-scale study from Pakistan showing high frequency of intracranial disease in Pakistani stroke patients. Our study showed that LAA is by far the most common mechanism for ischemic stroke in our series. This is in contrast to the other large ischemic stroke series from Pakistan, in which Syed et al17 report lacunar strokes as the most common stroke subtype followed by LAA (42.7% and 26.9%, respectively). A few other studies from India and Pakistan19,27,28,29 that have used TOAST taxonomy for classification also showed that lacunar strokes are the predominant stroke subtype with the exception of Kaul et al30 who have reported LAA as the major mechanism for ischemic stroke. All these are single center studies carried out on smaller number of subjects, which might explain the difference in subtypes. Another reason that can explain this difference is the availability of better vascular imaging modalities that have enhanced our understanding of LAA, resulting in more subjects being labeled with it. Table 8 shows the comparison of subtypes in various studies from India and Pakistan. Our study also shows that the outcomes of these ischemic stroke patients are poor in almost two thirds of patients. In-hospital mortality in our study was 13.2%, which is more than twice that reported from some other stroke registries.23,31,32 Possible reasons for this could be delay in accessing care after stroke, greater stroke severity, and suboptimal inpatient stroke care. Our study has several limitations. Although data were collected prospectively, there was missing information on some variables. Also, because it was an observational study, not all investigations were carried out on all subjects. This may have affected findings to some extent. Another limitation of the study was the nonavailability of outcomes after discharge. In-hospital mortality is higher than that reported in other studies, and it is expected that out of hospital outcomes may also have been worse. Despite these limitations, this is the largest reported series of ischemic stroke patients from Pakistan. It gives

important insights into the epidemiology of this devastating condition and reflects how over time the stroke subtypes have changed. The study highlights the importance of controlling risk factors, such as hypertension and dyslipidemia, which often go undiagnosed in resource poor settings. The implications of preventing strokes can be huge, because the outcomes are poor for the sufferers as shown in our study. Furthermore, our study also highlights deficiencies in secondary stroke prevention, which also warrants attention. We conclude that this kind of data is needed to better understand ischemic strokes and plan policy level interventions to address the risk factors. Acknowledgment: Author contributions: Bhojo A. Khealani contributed to the study design, grant proposal, data collection, data analysis, manuscript writing, and manuscript review. Maria Khan contributed to the study design, data analysis, manuscript writing, and manuscript review. Muhammad Tariq contributed to the study design, data collection, data analysis, and manuscript review. Abdul Malik contributed to the study design, data collection, data analysis, and manuscript review. Alam I. Siddiqi contributed to the study design, data collection, data analysis, and manuscript review. Safia Awan contributed to the study design, data analysis, manuscript writing, and manuscript review. Mohammad Wasay contributed to the study design, data collection, data analysis, manuscript writing, and manuscript review.

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STROKE IN PAKISTAN 11. Banks JL, Marotta CA. Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials a literature review and synthesis. Stroke 2007; 38:1091-1096. 12. Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41. 13. Basharat RA, Yousuf M, Iqbal J, et al. Frequency of known risk factors for stroke in poor patients admitted to Lahore General Hospital in 2000. Pak J Med Sci 2002;18:280-283. 14. Wasay KI, Khealani B, Afaq M. Temporal trends in risk factors and outcome of intracerebral hemorrhage over 18 years at a tertiary care hospital in Karachi, Pakistan. J Stroke Cerebrovasc Dis 2012;21:289-292. 15. Vohra EA, Ahmed WU, Ali M. Aetiology and prognostic factors of patients admitted for stroke. J Pak Med Assoc 2000;50:234-236. 16. Taj F, Zahid R, Syeda UE, et al. Risk factors of stroke in Pakistan: a dedicated stroke clinic experience. Can J Neurol Sci 2010;37:252-257. 17. Syed NA, Khealani BA, Ali S, et al. Ischemic stroke subtypes in Pakistan: the Aga Khan university stroke data bank. J Pak Med Assoc 2003;53:584-588. 18. Basharat Z, Mumtaz S, Rashid F, et al. Prevalence of risk factors of ischemic stroke in a local Pakistani population. High density lipoproteins, an emerging risk factor. Neurosciences (Riyadh) 2012;17:357-362. 19. Aquil N, Begum I, Ahmed A, et al. Risk factors in various subtypes of ischemic stroke according to TOAST criteria. J Coll Physicians Surg Pak 2011;21:280-283. 20. Farooq MU, Majid A, Reeves MJ, Birbeck GL. The epidemiology of stroke in Pakistan: past, present, and future. Int J Stroke 2009;4:381-389. 21. Khan NI, Naz L, Mushtaq S, et al. Ischemic stroke: prevalence of modifiable risk factors in male and female patients in Pakistan. Pak J Pharm Sci 2009;22:62-67. 22. Sridharan SE, Unnikrishnan JP, Sukumaran S, et al. Incidence, types, risk factors, and outcome of stroke in a

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24.

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27. 28.

29.

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Ischemic strokes in Pakistan: observations from the national acute ischemic stroke database.

The objective of this study was to establish a multicenter ischemic stroke registry, first of its kind in Pakistan, to provide insight into the epidem...
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