- Email: [email protected]
Risk Factors, Subtypes, and Outcome of Ischemic Stroke in Kuwait: A National Study
ARTICLE IN PRESS
Risk Factors, Subtypes, and Outcome of Ischemic Stroke in Kuwait: A National Study Jasem Y. Al-Hashel, MD, FRCPC, FAHS,*† Al-Alya Al-Sabah, BSc,‡ Samar F. Ahmed, MD,*§ Maha Al-Enezi, BSc,‡ Nour Al-Tawheid, BSc,‡ Zainab Al Mesailekh, BSc,‡ Jasmine Eliwa, BSc,‡ and Raed Alroughani, MD, FRCPC‖¶
Background and Purpose: Epidemiological studies of stroke burden in Kuwait are scarce. We aimed to identify the risk factors, subtypes, and outcome of ischemic stroke in the 6 major hospitals in Kuwait between 2008 and 2013. Methods: A cross-sectional survey was carried out using randomly selected ischemic stroke patients. It included data of sociodemographic status, stroke risk factors, stroke subtypes, treatment, and outcomes. Results: A total of 1257 ischemic stroke patients (811 men and 446 women; mean age 60.2 ± 13.1) were included. Smallartery ischemic stroke was the most common stroke subgroup (69.8%) whereas hypertension was the most prevalent risk factor (80.9%). History of heart disease was significantly associated (P < .001) with cardioembolic strokes (58.3%) compared to large-artery stroke (37.5%) and small-artery stroke (32.5%). Atrial fibrillation was significantly prevalent (P < .001) in cardioembolic stroke (54.2%) compared to large-artery stroke (13%) and small-artery stroke (7.6%). Presentation at ages less than 45 years was significantly (P < .001) associated with improved neurological status at discharge (82.6%) when compared to patients aged 45-70 years (78.5%) and more than 70 years (63.8%). Similar findings were observed at 6 months follow-up (78.4% versus 72.8% and 46%; P < .001). Cardioembolic stroke was significantly associated with higher mortality rates (25% versus 12.4% and 6.8%; P < .061) in large-vessel and small-vessel strokes, respectively. Conclusions: Small-artery ischemic stroke was the most common stroke subgroup, and hypertension was the most common risk factor. The outcome was better in younger patients. Cardioembolic stroke was associated with worse outcome. Key Words: Ischemic stroke—risk factors—outcome—cardioembolic—Kuwait. © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
From the *Department of Neurology, Ibn Sina Hospital, Safat, Kuwait; †Department of Medicine, Faculty of Medicine, Kuwait University, Jabriya, Kuwait; ‡Faculty of Medicine, Kuwait University, Jabriya, Kuwait; §Department of Neurology and Psychiatry, Minia University, Minia, Egypt; ‖Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait; and ¶Neurology Clinic, Dasman Diabetes Institute, Dasman, Kuwait. Received February 6, 2016; revision received April 16, 2016; accepted May 25, 2016. Address correspondence to Jasem Y. Al-Hashel, MD, FRCPC, FAHS, Department of Neurology, Ibn Sina Hospital, PO Box 25427, Safat 13115, Kuwait. E-mail: [email protected]. 1052-3057/$ - see front matter © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.05.038
Introduction The epidemiology of stroke is changing over time because of the increase in the proportion of the aging population and recent advances in the prevention and treatment of stroke.1 Continuing industrialization with the additional factor of unhealthy lifestyles has been shown to impact on the incidence and prevalence of stroke.2 Stroke is increasingly becoming a major health burden, with projections that mortality would nearly double by year 2030 in the Middle East.3 It is the leading cause of functional impairments, with 20% of survivors requiring institutional care after 3 months and 15%-30% being permanently disabled.4 Epidemiological studies have improved the
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■
1
ARTICLE IN PRESS J.Y. AL-HASHEL ET AL.
2
regulatory awareness of the burden of stroke on the population. The short-term and long-term consequences of stroke have been shown to impact the socioeconomic status of the affected patients and caregivers.1 Since stroke prevention appeared to be effective in reducing the burden of neurological disabilities, identification and quantification of stroke risk factors, particularly those that are modifiable, are of significant interest. There was a difference in the previous 2 studies that were conducted in Kuwait. The Al-shammri et al5 study showed that the most common stroke subtype is lacunar infarctions, in contrast to Abdul-Ghaffar et al6 study that reported large infarcts were the commonest. In addition, there was an alarming observation in Al-Shammri et al5 study, which revealed that the outcome in women was worse than that of men. This was different from the study done by AbdulGhaffar et al,6 which stated that there was no difference in the morbidity and mortality between the genders. The fact that both studies were done in Kuwait with different results needs further investigations. We aim to identify the risk factors, subtypes, and outcome of ischemic stroke in the 6 major hospitals in Kuwait between the years 2008 and 2013.
Methods Study Design and Population This cross-sectional study assessed ischemic stroke patients presented to the 6 major general hospitals of Kuwait between January 2008 and December 2013. It included patients with new and recurrent strokes. Stroke was defined according to the WHO (World Health Organization) stroke criteria.7 Transient ischemic attacks (TIAs), hemorrhagic strokes, stroke of undetermined etiology, and traumatic brain injury were excluded. Patients were randomly selected from the stroke list provided by the Health and Vital Statistics Division in the Ministry of Health.
Sample Size The sample size of 984 stroke patients was considered large enough to estimate a prevalence of any risk factor. Under the null hypothesis, we assumed 3% prevalence of such risk factor in the population of stroke patients, significance level (α) of .05, and 90% power to detect the hypothesized difference of 2%. To accommodate missing information on risk factors of interest in patients’ files, we inflated the final sample to 1257 stroke patients.
Data Collection Data were collected using patient’s hospital records. The survey consisted of 27 questions, which were divided into 5 major parts. The first part comprised 6 questions about sociodemographic data, the hospital in which the records were obtained, as well as the date of admission.
The second part involved 15 questions about stroke risk factors, previous history of stroke, and history of TIA, defined as an acute neurologic deficit of vascular origin lasting less than 24 hours.7 History of cardiac disease includes ischemic heart disease, arrhythmias, valvular heart disease, cardiomyopathy, congenital heart disease, and history of atrial fibrillation. Furthermore, a history of migraine, sickle cell anemia, smoking status, use of drugs (cocaine, amphetamines, and heroin), alcohol consumption, and oral contraception were all considered as stroke risk factors. Other risk factors that were assessed include hypertension (currently on antihypertensive treatment or blood pressure readings of 140/90 mm Hg during the period of hospitalization), diabetes mellitus (on treatment with either oral hypoglycemic or insulin before the insult, or by having fasting plasma glucose of more than 7.0 mmol/L, A1C = 6.5% or more, or a casual plasma glucose = 11.1 mmol/L or more), and dyslipidemia (currently on treatment or having a low-density lipoprotein cholesterol more than 200 mg/Dl).8 A family history of a stroke in a first-degree relative before the age of 70 was also considered.9 The third part was about the subtypes of stroke, which were defined according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria.10 The subtypes included cardioembolic ischemic stroke, large-artery atherosclerosis, and small-artery stroke. The type of stroke was obtained through imaging either by brain computed tomography scan or brain magnetic resonance imaging. The diagnosis of atherosclerosis was based on evidence of atherosclerosis in Doppler ultrasonography of carotid and the presence of risk factors (long-term diabetes, hypertension, and smoking).11 The fourth part surveyed the treatment, which included both acute (thrombolysis) and secondary prevention of ischemic stroke (antiplatelets, anticoagulants, and carotid endarterectomy). The last part assessed the severity at onset and the neurological outcomes at discharge, and at 1 and 6 months post stroke. The severity was based on modified Rankin Scale, in which grade 1 refers to no deficit, and grade II, grade III, and grades IV and V are equivalent to our mild, moderate, and severe categories, respectively.12 The outcome was classified as recovered, improved, no improvement, and death, which were ascertained at discharge, in 1 and 6 months duration. The degree of improvement or lack of it was correlated by comparing the power at the onset to that of the outcome at discharge, and after 1 and 6 months.12 Death certificates were additionally examined for the etiology of mortality.
Statistical Analysis Statistical program SPSS version 23.0 (IBM SPSS Statistics 23, IBM Corporation, Armonk, NY, 2014) was used to analyze the data. Categorical variables are presented
ARTICLE IN PRESS ISCHEMIC STROKE IN KUWAIT
3
as number (%) and continuous variables as mean (standard deviation). Chi-square test was used to test the association between categorical variables whereas Fisher’s exact test was used whenever the validity of chisquare test was violated. Age was compared among the stroke subtypes using one-way analysis of variance. A P value of .05 was considered as statistically significant. The Ethical Committee of the Ministry of Health approved the study.
Results A total of 1257 patients with ischemic stroke (811 men and 446 women) were included. Patients’ characteristics by stroke subtype were summarized in Table 1. Ku-
waitis were the largest ethnic group (45.7%), followed by non-Kuwaiti Arabs (30.6%) and non-Kuwaiti non-Arabs (23.5%). Small-artery ischemic stroke was the most common stroke subtype (69.8%), followed by large-artery ischemic stroke (26.3%) and cardioembolic stroke (3.8%). There were no significant differences in the distribution of age, gender, nationality, marital status, and physical status between stroke subtypes. The proportion of men was high in all stroke subtypes whereas the proportion of Kuwaitis was relatively similar in the 3 subtypes. Among the modifiable risk factors, previous history of cardiac disease, previous history of atrial fibrillation, and diabetes were significantly different among various stroke subtypes. History of smoking was slightly higher (P < .072) in patients with large-artery ischemic stroke (37.5%)
Table 1. Summary of patient characteristics by stroke subtype Characteristics
All
Large vessel
Small vessel
Cardioembolic
N Gender Male Female Age in years <45 45-70 >70 Mean (SD) Nationality Kuwaiti Non-Kuwaiti (Arabs) Non-Kuwaiti (non-Arabs) Marital status Single Married Divorced/widowed Physical status Normal Overweight/obese Previous history of stroke Previous history of TIA Previous history of cardiac disease Previous history of atrial fibrillation Previous history of migraine Hypertension Diabetes Dyslipidemia Ever smoked Alcohol use Drug use Contraceptive drug use Family history of stroke (first-degree relatives)
1257 (100)
331 (26.3)
878 (69.8)
48 (3.8)
811 (64.5) 446 (35.5)
211 (63.7) 120 (36.3)
572 (65.1) 306 (34.9)
28 (58.3) 20 (41.7)
149 (11.9) 812 (64.6) 296 (23.5) 60.2 (13.1)
51 (15.4) 208 (62.8) 72 (21.8) 58.9 (13.8)
92 (10.5) 573 (65.3) 213 (24.3) 60.7 (12.8)
6 (12.5) 31 (64.6) 11 (22.9) 59.0 (12.8)
574 (45.7) 387 (30.6) 296 (23.5)
153 (46.2) 86 (26.0) 92 (27.8)
398 (45.3) 283 (32.2) 197 (22.4)
23 (47.9) 18 (37.5) 7 (14.6)
33 (2.6) 1181 (94.0) 43 (3.4)
11 (3.3) 307 (92.7) 13 (3.9)
20 (2.3) 831 (94.6) 27 (3.1)
2 (4.2) 43 (89.6) 3 (6.3)
605 (48.1) 652 (51.9) 428 (34.0) 164 (13.0) 437 (34.8) 136 (10.8) 9 (.7) 1017 (80.9) 817 (65.0) 337 (26.8) 435 (34.6) 44 (3.5) 2 (.2) 10 (2.3) 20 (1.6)
158 (47.7) 173 (52.3) 110 (33.2) 37 (11.2) 124 (37.5) 43 (13.0) 6 (1.8) 260 (78.5) 222 (67.1) 85 (25.7) 124 (37.5) 17 (5.1) 1 (.3) 3 (2.5) 5 (1.5)
420 (47.8) 458 (52.2) 304 (34.6) 121 (13.8) 285 (32.5) 67 (7.6) 3 (.3) 722 (82.2) 572 (65.1) 244 (27.8) 301 (34.3) 27 (3.1) 1 (.1) 7 (2.3) 15 (1.7)
27 (56.3) 21 (43.8) 14 (29.2) 6 (12.5) 28 (58.3) 26 (54.2) 0 (.0) 35 (72.9) 23 (47.9) 8 (16.7) 10 (20.8) 0 (.0) 0 (.0) 0 (.0) 0 (.0)
P value
.594*
.213*
.088† .075*
.505‡
.517*
Abbreviations: SD, standard deviation; TIA, transient ischemic attack. P values are generated using chi-square test, one-way analysis of variance (ANOVA), and Fisher’s exact test. *Chi-square test. †One-way ANOVA. ‡Fisher’s exact test.
.692* .485* .001* <.001* .041† .124* .034* .206* .072* .089* .512† .999† .648*
ARTICLE IN PRESS J.Y. AL-HASHEL ET AL.
4
Table 2. Treatment in patients by stroke subtype
Treatment
All
Large vessel n (%)
Small vessel n (%)
Cardioembolic n (%)
P value
Antiplatelet Anticoagulant Carotid endarterectomy Thrombolysis
1240 (98.6) 182 (14.5) 6 (.5) 5 (.4)
323 (97.6) 57 (17.2) 3 (.9) 3 (.9)
874 (99.5) 100 (11.4) 1 (.1) 1 (.1)
43 (89.6) 25 (52.1) 2 (4.2) 1 (2.1)
<.001* <.001* .003† .025†
Numbers may not add up to the total because of combinations of treatment. P values are generated using chi-square test and Fisher’s exact test. *Chi-square test. †Fisher’s exact test.
compared to patients with cardioembolic (20.8%) and smallartery ischemic strokes (34.3%). A family history of stroke in a first-degree relative was reported in 20 patients (1.6%), most of whom had small-vessel stroke (15 of 20). Only .4% of patients received thrombolysis as an acute treatment, most of whom had cardioembolic stroke, whereas most patients who had small-artery and largeartery ischemic strokes (98.6%) received antiplatelets, as shown in Table 2. Anticoagulation was prescribed in 14.5% of our cohort, primarily in patients with cardioembolic strokes (52.1%). Carotid endarterectomy was only performed in .5% (n = 6) of patients with cardioembolic stroke.
Stroke severity at onset, length of hospitalization, and outcome at discharge, and at 1 and 6 months followup, were outlined in Table 3. Neurological outcome at onset was considered severe in 50% and 46.2% of patients with cardioembolic and large-vessel ischemic strokes, respectively. Furthermore, patients with cardioembolic stroke had longer hospital stay. A total of 132 (10.5%) patients had complete recovery whereas 811 (64.5%) patients had improvement in their condition at discharge. Smallartery ischemic stroke was associated with better outcome at discharge when compared to other stroke subtypes (P < .001). A total of 56 (4.5%) patients died during their hospital stay.
Table 3. Stroke severity, length of hospitalization, and outcome in stroke subtype
Parameter Stroke severity (motor deficit at onset) Mild Moderate Severe Length of hospitalization, median (IQR) Outcome at discharge Recovered Improved Not improved Died Outcome at 1 month follow-up (n = 634) Recovered Improved Not improved Died Outcome at 6 months follow-up (n = 561) Recovered Improved Not improved Died
All
Large vessel n (%)
Small vessel n (%)
Cardioembolic n (%)
403 (32.1) 428 (34.0) 426 (33.9) 6 (4-11)
71 (21.5) 107 (32.3) 153 (46.2) 8 (4-17)
319 (36.3) 310 (35.3) 249 (28.4) 5 (4-9)
13 (27.1) 11 (22.9) 24 (50.0) 10 (6-25)
132 (10.5) 811 (64.5) 258 (20.5) 56 (4.5)
23 (6.9) 203 (61.3) 82 (24.8) 23 (6.9)
106 (12.1) 580 (66.1) 165 (18.8) 27 (3.1)
3 (6.3) 28 (58.3) 11 (22.9) 6 (12.5)
155 (24.4) 253 (39.9) 169 (26.7) 57 (9.0)
25 (15.2) 63 (38.2) 54 (32.7) 23 (13.9)
120 (27.4) 181 (41.3) 109 (24.9) 28 (6.4)
10 (32.3) 9 (29.0) 6 (19.4) 6 (19.4)
185 (33.0) 179 (31.9) 135 (24.1) 62 (11.1)
32 (23.2) 40 (29.0) 42 (30.4) 24 (17.4)
142 (35.9) 134 (33.8) 88 (22.2) 32 (8.1)
11 (40.7) 5 (18.5) 5 (18.5) 6 (22.2)
P value <.001*
<.001† <.001*
<.001*
.001†
Abbreviation: IQR, interquartile range. Data are column percentages. P values are generated using chi-square test and Fisher’s exact test. *Chi-square test. †Fisher’s exact test.
ARTICLE IN PRESS ISCHEMIC STROKE IN KUWAIT
5
Table 4. Outcome by demographic characteristics Age in years
Gender
Outcome
<45
45-70
>75
At discharge, n Recovered Improved Not improved Died P value At 1 month, n Recovered Improved Not improved Died P value At 6 months, n Recovered Improved Not improved Died P value
149 15 (10.1) 108 (72.5) 23 (15.4) 3 (2.0)
812 90 (11.1) 547 (67.4) 149 (18.3) 26 (3.2) <.001 398 108 (27.1) 175 (44.0) 89 (22.4) 26 (6.5) <.001 352 128 (36.4) 128 (36.4) 68 (19.3) 28 (8.0) <.001
296 27 (9.1) 156 (52.7) 86 (29.1) 27 (9.1)
51 20 (39.2) 17 (33.3) 11 (21.6) 3 (5.9) 37 23 (62.2) 6 (16.2) 5 (13.5) 3 (8.1)
185 27 (14.6) 61 (33.0) 69 (37.3) 28 (15.1) 172 34 (19.8) 45 (26.2) 62 (36.0) 31 (18.0)
Male
Female
811 446 90 (11.1) 42 (9.4) 539 (66.5) 272 (61.0) 151 (18.6) 107 (24.0) 31 (3.8) 25 (5.6) .042 370 264 98 (26.5) 57 (21.6) 145 (39.2) 108 (40.9) 96 (25.9) 73 (27.7) 31 (8.4) 26 (9.8) .539 319 242 114 (35.7) 71 (29.3) 98 (30.7) 81 (33.5) 75 (23.5) 60 (24.8) 32 (10.0) 30 (12.4) .419
Nationality
Kuwaiti 574 71 (12.4) 329 (57.3) 144 (25.1) 30 (5.2) 391 93 (23.8) 146 (37.3) 122 (31.2) 30 (7.7) 359 114 (31.8) 111 (30.9) 100 (27.9) 34 (9.5)
Non-Kuwaiti Arabs
Non-Kuwaiti non-Arabs
387 35 (9.0) 270 (69.8) 66 (17.1) 16 (4.1) <.001 160 39 (24.4) 73 (45.6) 32 (20.0) 16 (10.0) .043 142 42 (29.6) 54 (38.0) 29 (20.4) 17 (12.0) .003
296 26 (8.8) 212 (71.6) 48 (16.2) 10 (3.4) 83 23 (27.7) 34 (41.0) 15 (18.1) 11 (13.3) 60 29 (48.3) 14 (23.3) 6 (10.0) 11 (18.3)
Data are column percentages. P values are generated using chi-square test to compare between gender and outcome at discharge, and at 1 and 6 months follow-up.
The age, gender, and nationality of the patients showed a significant difference in the outcome at discharge (Table 4). Higher recovery or improvement rates were observed in the younger age group, men, and nonKuwaiti patients (Table 4). Similar findings were observed at 1 and 6 months follow-up according to age and nationality. However, the difference in gender was not significant. When the outcome of patients according to stroke severity at onset was assessed, there was a significant association between stroke severity and the outcome of patients at the 3 stages (Table 5). Worse neurological outcomes were observed among patients with severe stroke compared to mild or moderate groups. When the outcome by stroke severity and the stroke subtypes were stratified, the proportion of patients in the outcome was not significantly different among the subtypes in any of the stroke severity groups (Table 6).
Discussion Small-vessel ischemic stroke was the most prevalent (69.8%) subtype in our study, which was in line with previous reports from Kuwait (59.7%),5 Japan (56%),13 and Norway (75.2%).14 However, lower rates of large-vessel strokes were observed in our cohort (26.3%) when compared to reports in previous studies in Kuwait (46.5%),6 German (50%),15 and Latin America (32.4%).16 This discrepancy might be due to methodological differences, which
included different use of diagnostic criteria, and population studied. A high rate of small-vessel stroke in our study could be partly explained by the high prevalence of hypertension and diabetes in our population. However, other studies report no significant differences in risk factors associated with different stroke subtypes.17,18 We observed a male predominance (64.5%) in all subtypes of stroke, which was similarly reported in previous regional and international studies in Qatar (73%),19 Lebanon (60%),20 Italy (61.6%),21 Germany (57.6%),22 and Norway (69%).14 The mean age of stroke in our study was 60.2 years, which was similar to other reports (63.2 years in Lebanon,20 59 years in a prospective Arabian Gulf study).23 However, higher mean age of patients with stroke was reported in other international studies (65.9 in German,22 70.1 years in Norway,14 and 70.6 in Brooklyn, New York).24 Younger population and differences in genetic predisposition in the Middle East could partly explain this. Hypertension was the most common risk factor (80%), followed by diabetes (65%), cardiac disease (34.8%), smoking (34.6%), history of previous stroke (34%), and dyslipidemia (26.8%). This raises the importance of effective interventions for prevention and treatment of these risk factors among target population to reduce the burden of stroke. Our results are in agreement with previous Kuwait studies5,6,25 as well as other regional26,27 and international studies.21,22,28 However, few discrepancies are worth noting. Diabetes comprises 65% in this study, which
ARTICLE IN PRESS J.Y. AL-HASHEL ET AL.
6
Table 5. Outcome in stroke patients according to severity of stroke at onset
Outcome at discharge, n Recovered Improved Not improved Died P value Outcome at 1 month, n Recovered Improved Not improved Died P value Outcome at 6 months, n Recovered Improved Not improved Died P value
All
Mild
Moderate
Severe
1257 10.5 64.5 20.5 4.5
403 24.1 68.0 6.7 1.2
428 6.3 73.4 18.2 2.1
426 1.9 52.3 35.9 9.9
634 24.4 39.9 26.7 9.0
198 53.0 38.4 6.1 2.5
191 18.3 53.4 23.6 4.7
561 33.0 31.9 24.1 11.1
180 60.0 33.3 3.9 2.8
167 32.3 42.5 19.8 5.4
<.001 245 6.1 30.6 45.7 17.6 <.001 214 10.7 22.4 44.4 22.4 <.001
Data are column percentages. P values are generated using chi-square test to compare between severity of stroke at onset and outcome at discharge, and at 1 and 6 months follow-up.
Table 6. Outcome by stroke severity at onset and stroke subtypes Stroke severity at onset
Outcome At discharge, n Recovered Improved Not improved Died P value At 1 month, n Recovered Improved Not improved Died P value At 6 months, n Recovered Improved Not improved Died P value
Mild
Moderate
Severe
Stroke subtypes
Stroke subtypes
Stroke subtypes
Large vessel
Small vessel
Cardioembolic
71 22.5 73.2 2.8 1.4
319 24.8 66.5 7.5 1.3
13 15.4 76.9 7.7 .0
30 46.7 43.3 6.7 3.3
159 53.5 37.7 6.3 2.5
24 54.2 37.5 4.2 4.2
148 59.5 33.8 4.1 2.7
Large vessel
Small vessel
Cardioembolic
107 5.6 71.0 20.6 2.8
310 6.5 74.5 17.1 1.9
11 9.1 63.6 27.3 .0
9 66.7 33.3 .0 .0
45 20.0 46.7 26.7 6.7
140 16.4 57.1 22.1 4.3
8 87.5 12.5 .0 .0
39 35.9 30.8 25.6 7.7
123 30.1 47.2 17.9 4.9
.691
153
Small vessel
.7 49.0 37.9 12.4
249 2.8 55.0 35.3 6.8
6 50.0 16.7 33.3 .0
90 2.2 32.2 44.4 21.1
139 8.6 29.5 48.9 12.9
5 60.0 20.0 20.0 .0
75 6.7 25.3 41.3 26.7
125 13.6 20.8 48.0 17.6
.781
.948
.745
Large vessel
Data are column percentages. P values are generated using Fisher’s exact test.
24 .0 45.8 28.2 25.0 .061
.256
.398
Cardioembolic
16 6.3 31.3 25.0 37.5 .059 14 7.1 21.4 28.6 42.9 .209
ARTICLE IN PRESS ISCHEMIC STROKE IN KUWAIT
was much higher than in western studies as in German (28.5%),22 Norway (24.7%),14 and Italy (17%).21 This dissimilarity is most probably due to heritable causes and the more sedentary lifestyle in Kuwait. A higher frequency of previous stroke (34%) than in other countries was observed (28% in Italy21 and 22.8% in Germany)22; however, our results were lower than 42.9% in Brazil.28 These differences could be explained by genetic, environmental, or sociocultural factors. There was no association between the different subtypes of ischemic stroke and a previous attack in our study, which was similar to the German study.22 A history of TIA (13%) in our study was similar to the studies reported from Bahrain (11%)26 and Germany (12.7%).22 Nevertheless, no association was found between the different subtypes and previous history of TIA in our study, which was similar to Rochester study.29 On the contrary, a German study revealed a significant association between previous TIA and large-vessel stroke (20%).22 These differences could be attributed to the variation in case ascertainment and classification. Alcohol consumption was the least frequent risk factor in our cohort. This is likely because alcohol consumption is illegal in Kuwait. Significant differences were found among stroke subtypes; large-vessel stroke had more frequent diabetes and cardioembolic stroke had more frequent history of cardiac disease and atrial fibrillation. Hypertension and dyslipidemia were more prevalent in patients with small-vessel stroke; however, the difference was nonsignificant. In our cohort, diabetes was significantly associated with large-artery stroke subtype. It has been shown that diabetes was associated with increased level of coagulation factors and hyperinsulinemia associated with the development of large-vessel stroke.13 Small-vessel ischemic stroke in our cohort was significantly associated with dyslipidemia. Higher serum cholesterol level was shown to be associated with a higher prevalence of minor strokes.30 Thrombolysis was only used at a rate of .4%; this is similar to the Arabian Gulf study (.8%).24 The overall thrombolysis rate in our patients was below that of other international studies in Brazil (2.7%),31 Germany (3.6%),22 and Cleveland, USA (6.9%).32 Most patients with stroke in Kuwait were treated in public hospitals, where the thrombolysis protocols were not yet routinely available except in 2 hospitals at the time of conducting our study. Another obstacle to thrombolysis in Kuwait is the lack of stroke awareness, leading to delays in stroke triage. Patients with cardioembolic stroke were more likely to receive thrombolytic therapy in our cohort. Cardioembolic stroke was the most significant subtype associated with worse outcome, which was in agreement with previous studies.21,22 Favorable outcome at discharge was found to be significant with small-vessel ischemic stroke. On the other hand, mortality was significantly higher in cardioembolic stroke correlating with
7
disease severity. Our result was in agreement with previous western studies.20,29,33,34 There is no significant difference between men and women with regard to the outcome. As expected, an increase in age was significantly associated with poor outcome and mortality. Kuwaitis had worse outcomes and higher mortality rates than non-Kuwaitis at discharge. This could be explained by the differences in the demographics of expats who were young and in the working force. Our study had several limitations. First, it was retrospective in nature using chart review of patient’s records. Second, it was a hospital-based rather than a populationbased study. Third, the severity and outcome assessments were performed through examining motor deficits in both lower and upper limbs without the inclusion of the affection of activities of daily living, which are rather comprehensive assessment measures of functionality. This assessment was subjective and there was a high rate of intrarater variability among physicians. However, the strength of our result relies on being one of the largest cross-sectional studies conducted at the national level in the Middle East counties.
Conclusion The epidemiology of stroke in Kuwait is comparable to other regional and international areas. Small-artery ischemic stroke was the most common stroke subtype, and hypertension is the most common risk factor in Kuwait. There were differences in the prevalence of major risk factors among the stroke subtypes, demonstrating that knowledge of pathophysiology is essential for the proper management of these patients. Increasing age and embolic stroke subtypes were associated with an adverse outcome. There is an urgent need to design a stroke registration system in Kuwait for a better health planning. Preventive efforts should be directed at decreasing the number of new strokes by a better control of risk factors, particularly hypertension, diabetes, and atrial fibrillation in elderly patients, to decrease the burden of stroke. Our data may be helpful to the health authorities and may facilitate formulating new policies or recommendations with respect to the treatment of acute stroke focusing on the public awareness, modifiable risk factors, and the need for collaboration between neurology and vascular surgery specialists, along with reduction of any logistical hurdles to thrombolysis.
References 1. Kadojic D, Dikanovic M, Bitunjac M, et al. Epidemiology of stroke. Period Biol 2012;114:253-257. 2. Kim AS, Johnston SC. Global variation in the relative burden of stroke and ischemic heart disease. Circulation 2011;124:314-323. 3. Tran J, Mirzaei M, Anderson L, et al. The epidemiology of stroke in the Middle East and North Africa. J Neurol Sci 2010;295:38-40.
ARTICLE IN PRESS 8 4. Murray CJL, Lopez AD. The global burden of disease: a comprehensive assessment of morality and disability from diseases, injuries and risk factors in 1990 and projected to 2020. Boston: Harvard University Press, 1996. 5. Al-Shammri S, Shahid Z, Ghali A, et al. Risk factors, subtypes and outcome of ischaemic stroke in Kuwait—a hospital-based study. Med Princ Pract 2003;12:218-223. 6. Abdul-Ghaffar NU, El-Sonbaty MR, Abdul-Baky MSE, et al. Stroke in Kuwait: a three-year prospective study. Neuroepidemiology 1997;16:40-47. 7. WHO, World Health Organization. Cerebrovascular diseases: prevention, treatment and rehabilitation. World Health Organ Tech Rep Ser 1971;469:1-57. 8. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke 2011;42:227-276. 9. Jood K, Ladenvall C, Rosengren A, et al. Family history in ischemic stroke before 70 years of age: the Sahlgrenska Academy study on ischemic stroke. Stroke 2005;36:13831397. 10. Adams HP Jr, 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. 11. Kashinkunti MD, Mantri N, Dhananjaya MA. Retrospective study of stroke in young adults from tertiary care hospital. Scholars J Appl Med Sci 2013;1:506-510. 12. Bonita R, Beaglehole R. Recovery of motor function after stroke. Stroke 1988;19:1497-1500. 13. Tanizaki Y, Kiyohara Y, Kato I, et al. Incidence and risk factors for subtypes of cerebral infarction in a general population: the Hisayama study. Stroke 2000;31:2616-2622. 14. Altmann N, Thommessen B, Rønning OM, et al. Blood pressure differences between patients with lacunar and non lacunar infarcts. Brain Behav 2015;5:e00353. 15. Petty GW, Brown RD Jr, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke 1999;30:2513-2516. 16. Porcello Marrone LC, Diogo LP, de Oliveira FM, et al. Risk factors among stroke subtypes in Brazil. J Stroke Cerebrovasc Dis 2013;22:32-35. 17. Jackson C, Sudlow C. Comparing risks of death and recurrent vascular events between lacunar and nonlacunar infarction. Brain 2005;128:2507-2517. 18. Mohan KM, Crichton SL, Grieve AP, et al. Frequency and predictors for the risk of stroke recurrence up to 10 years after stroke: the South London stroke register. J Neurol Neurosurg Psychiatry 2009;80:1012-1018. 19. Khan FY, Yasin M, bu-Khattab M, et al. Stroke in Qatar: a first prospective hospital-based study of acute stroke. J Stroke Cerebrovasc Dis 2008;17:69-78.
J.Y. AL-HASHEL ET AL. 20. Lahoud N, Salameh P, Saleh N, et al. Prevalence of Lebanese stroke survivors: a comparative pilot study. J Epidemiol Glob Health 2015;doi:10.1016/j.jegh.2015.10.001; in press. 21. Corso G, Bottacchi E, Giardini G, et al. Epidemiology of stroke in Northern Italy: the Cerebrovascular Aosta Registry, 2004-2008. Neurol Sci 2013;34:1071-1081. 22. Grau AJ, Weimar C, Buggle F, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke 2001;32:2559-2566. 23. Deleu D, Inshasi J, Akhtar N, et al. Risk factors, management and outcome of subtypes of ischemic stroke: a stroke registry from the Arabian Gulf. J Neurol Sci 2011;300:142-147. 24. Sharma M, Helzner E, Sinert R, et al. Patient characteristics affecting stroke identification by emergency medical service providers in Brooklyn, New York. Intern Emerg Med 2016;11:229-236. 25. Ashkanani A, Hassan KA, Lamdhade S. Risk factors of stroke patients admitted to a general hospital in Kuwait. Int J Neurosci 2013;123:89-92. 26. Bahou Y, Hamid H, Raqab MZ. Ischemic stroke in Jordan 2000 to 2002: a two-year, hospital-based study. J Stroke Cerebrovasc Dis 2004;13:81-84. 27. Al-Jishi AA, Mohan PK. Profile of stroke in Bahrain. Neurosiences 2000;5:30-34. 28. Freitas de Carvalho JJ, Alves MB, Viana GAA, et al. Stroke epidemiology, patterns of management, and outcomes in Fortaleza, Brazil. A hospital-based multicenter prospective study. Stroke 2011;42:3341-3346. 29. Petty GW, Brown RD, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke 2000;31:1062-1068. 30. Olsen TS, Christensen RHB, Kammersgaard LP, et al. Higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality: ten-year follow-up of ischemic strokes in the Copenhagen stroke study. Stroke 2007;38:2646-2651. 31. Conforto AB, Paulo RB, Patroclo CB, et al. Stroke management in a university hospital in the largest South American City. Arq Neuropsiquiatr 2008;66:308311. 32. Katzan IL, Hammer MD, Hixson ED, et al. Utilization of intravenous tissue plasminogen activator for acute ischemic stroke. Arch Neurol 2004;61:346-350. 33. Lavados PM, Sacks C, Prina L, et al. Incidence, casefatality rate, and prognosis of ischaemic stroke subtypes in a predominantly Hispanic-Mestizo population in Iquique, Chile (PISCIS project): a community-based incidence study. Lancet Neurol 2007;6:140-148. 34. Lange MC, Cabral NL, Moro CHC, et al. Incidence and mortality of ischemic stroke subtypes in Joinville, Brazil: a population-based study. Arq Neuropsiquiatr 2015;73:648-654.
Risk Factors, Subtypes, and Outcome of Ischemic Stroke in Kuwait: A National Study Jasem Y. Al-Hashel, MD, FRCPC, FAHS,*† Al-Alya Al-Sabah, BSc,‡ Samar F. Ahmed, MD,*§ Maha Al-Enezi, BSc,‡ Nour Al-Tawheid, BSc,‡ Zainab Al Mesailekh, BSc,‡ Jasmine Eliwa, BSc,‡ and Raed Alroughani, MD, FRCPC‖¶
Background and Purpose: Epidemiological studies of stroke burden in Kuwait are scarce. We aimed to identify the risk factors, subtypes, and outcome of ischemic stroke in the 6 major hospitals in Kuwait between 2008 and 2013. Methods: A cross-sectional survey was carried out using randomly selected ischemic stroke patients. It included data of sociodemographic status, stroke risk factors, stroke subtypes, treatment, and outcomes. Results: A total of 1257 ischemic stroke patients (811 men and 446 women; mean age 60.2 ± 13.1) were included. Smallartery ischemic stroke was the most common stroke subgroup (69.8%) whereas hypertension was the most prevalent risk factor (80.9%). History of heart disease was significantly associated (P < .001) with cardioembolic strokes (58.3%) compared to large-artery stroke (37.5%) and small-artery stroke (32.5%). Atrial fibrillation was significantly prevalent (P < .001) in cardioembolic stroke (54.2%) compared to large-artery stroke (13%) and small-artery stroke (7.6%). Presentation at ages less than 45 years was significantly (P < .001) associated with improved neurological status at discharge (82.6%) when compared to patients aged 45-70 years (78.5%) and more than 70 years (63.8%). Similar findings were observed at 6 months follow-up (78.4% versus 72.8% and 46%; P < .001). Cardioembolic stroke was significantly associated with higher mortality rates (25% versus 12.4% and 6.8%; P < .061) in large-vessel and small-vessel strokes, respectively. Conclusions: Small-artery ischemic stroke was the most common stroke subgroup, and hypertension was the most common risk factor. The outcome was better in younger patients. Cardioembolic stroke was associated with worse outcome. Key Words: Ischemic stroke—risk factors—outcome—cardioembolic—Kuwait. © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
From the *Department of Neurology, Ibn Sina Hospital, Safat, Kuwait; †Department of Medicine, Faculty of Medicine, Kuwait University, Jabriya, Kuwait; ‡Faculty of Medicine, Kuwait University, Jabriya, Kuwait; §Department of Neurology and Psychiatry, Minia University, Minia, Egypt; ‖Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait; and ¶Neurology Clinic, Dasman Diabetes Institute, Dasman, Kuwait. Received February 6, 2016; revision received April 16, 2016; accepted May 25, 2016. Address correspondence to Jasem Y. Al-Hashel, MD, FRCPC, FAHS, Department of Neurology, Ibn Sina Hospital, PO Box 25427, Safat 13115, Kuwait. E-mail: [email protected]. 1052-3057/$ - see front matter © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.05.038
Introduction The epidemiology of stroke is changing over time because of the increase in the proportion of the aging population and recent advances in the prevention and treatment of stroke.1 Continuing industrialization with the additional factor of unhealthy lifestyles has been shown to impact on the incidence and prevalence of stroke.2 Stroke is increasingly becoming a major health burden, with projections that mortality would nearly double by year 2030 in the Middle East.3 It is the leading cause of functional impairments, with 20% of survivors requiring institutional care after 3 months and 15%-30% being permanently disabled.4 Epidemiological studies have improved the
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■
1
ARTICLE IN PRESS J.Y. AL-HASHEL ET AL.
2
regulatory awareness of the burden of stroke on the population. The short-term and long-term consequences of stroke have been shown to impact the socioeconomic status of the affected patients and caregivers.1 Since stroke prevention appeared to be effective in reducing the burden of neurological disabilities, identification and quantification of stroke risk factors, particularly those that are modifiable, are of significant interest. There was a difference in the previous 2 studies that were conducted in Kuwait. The Al-shammri et al5 study showed that the most common stroke subtype is lacunar infarctions, in contrast to Abdul-Ghaffar et al6 study that reported large infarcts were the commonest. In addition, there was an alarming observation in Al-Shammri et al5 study, which revealed that the outcome in women was worse than that of men. This was different from the study done by AbdulGhaffar et al,6 which stated that there was no difference in the morbidity and mortality between the genders. The fact that both studies were done in Kuwait with different results needs further investigations. We aim to identify the risk factors, subtypes, and outcome of ischemic stroke in the 6 major hospitals in Kuwait between the years 2008 and 2013.
Methods Study Design and Population This cross-sectional study assessed ischemic stroke patients presented to the 6 major general hospitals of Kuwait between January 2008 and December 2013. It included patients with new and recurrent strokes. Stroke was defined according to the WHO (World Health Organization) stroke criteria.7 Transient ischemic attacks (TIAs), hemorrhagic strokes, stroke of undetermined etiology, and traumatic brain injury were excluded. Patients were randomly selected from the stroke list provided by the Health and Vital Statistics Division in the Ministry of Health.
Sample Size The sample size of 984 stroke patients was considered large enough to estimate a prevalence of any risk factor. Under the null hypothesis, we assumed 3% prevalence of such risk factor in the population of stroke patients, significance level (α) of .05, and 90% power to detect the hypothesized difference of 2%. To accommodate missing information on risk factors of interest in patients’ files, we inflated the final sample to 1257 stroke patients.
Data Collection Data were collected using patient’s hospital records. The survey consisted of 27 questions, which were divided into 5 major parts. The first part comprised 6 questions about sociodemographic data, the hospital in which the records were obtained, as well as the date of admission.
The second part involved 15 questions about stroke risk factors, previous history of stroke, and history of TIA, defined as an acute neurologic deficit of vascular origin lasting less than 24 hours.7 History of cardiac disease includes ischemic heart disease, arrhythmias, valvular heart disease, cardiomyopathy, congenital heart disease, and history of atrial fibrillation. Furthermore, a history of migraine, sickle cell anemia, smoking status, use of drugs (cocaine, amphetamines, and heroin), alcohol consumption, and oral contraception were all considered as stroke risk factors. Other risk factors that were assessed include hypertension (currently on antihypertensive treatment or blood pressure readings of 140/90 mm Hg during the period of hospitalization), diabetes mellitus (on treatment with either oral hypoglycemic or insulin before the insult, or by having fasting plasma glucose of more than 7.0 mmol/L, A1C = 6.5% or more, or a casual plasma glucose = 11.1 mmol/L or more), and dyslipidemia (currently on treatment or having a low-density lipoprotein cholesterol more than 200 mg/Dl).8 A family history of a stroke in a first-degree relative before the age of 70 was also considered.9 The third part was about the subtypes of stroke, which were defined according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria.10 The subtypes included cardioembolic ischemic stroke, large-artery atherosclerosis, and small-artery stroke. The type of stroke was obtained through imaging either by brain computed tomography scan or brain magnetic resonance imaging. The diagnosis of atherosclerosis was based on evidence of atherosclerosis in Doppler ultrasonography of carotid and the presence of risk factors (long-term diabetes, hypertension, and smoking).11 The fourth part surveyed the treatment, which included both acute (thrombolysis) and secondary prevention of ischemic stroke (antiplatelets, anticoagulants, and carotid endarterectomy). The last part assessed the severity at onset and the neurological outcomes at discharge, and at 1 and 6 months post stroke. The severity was based on modified Rankin Scale, in which grade 1 refers to no deficit, and grade II, grade III, and grades IV and V are equivalent to our mild, moderate, and severe categories, respectively.12 The outcome was classified as recovered, improved, no improvement, and death, which were ascertained at discharge, in 1 and 6 months duration. The degree of improvement or lack of it was correlated by comparing the power at the onset to that of the outcome at discharge, and after 1 and 6 months.12 Death certificates were additionally examined for the etiology of mortality.
Statistical Analysis Statistical program SPSS version 23.0 (IBM SPSS Statistics 23, IBM Corporation, Armonk, NY, 2014) was used to analyze the data. Categorical variables are presented
ARTICLE IN PRESS ISCHEMIC STROKE IN KUWAIT
3
as number (%) and continuous variables as mean (standard deviation). Chi-square test was used to test the association between categorical variables whereas Fisher’s exact test was used whenever the validity of chisquare test was violated. Age was compared among the stroke subtypes using one-way analysis of variance. A P value of .05 was considered as statistically significant. The Ethical Committee of the Ministry of Health approved the study.
Results A total of 1257 patients with ischemic stroke (811 men and 446 women) were included. Patients’ characteristics by stroke subtype were summarized in Table 1. Ku-
waitis were the largest ethnic group (45.7%), followed by non-Kuwaiti Arabs (30.6%) and non-Kuwaiti non-Arabs (23.5%). Small-artery ischemic stroke was the most common stroke subtype (69.8%), followed by large-artery ischemic stroke (26.3%) and cardioembolic stroke (3.8%). There were no significant differences in the distribution of age, gender, nationality, marital status, and physical status between stroke subtypes. The proportion of men was high in all stroke subtypes whereas the proportion of Kuwaitis was relatively similar in the 3 subtypes. Among the modifiable risk factors, previous history of cardiac disease, previous history of atrial fibrillation, and diabetes were significantly different among various stroke subtypes. History of smoking was slightly higher (P < .072) in patients with large-artery ischemic stroke (37.5%)
Table 1. Summary of patient characteristics by stroke subtype Characteristics
All
Large vessel
Small vessel
Cardioembolic
N Gender Male Female Age in years <45 45-70 >70 Mean (SD) Nationality Kuwaiti Non-Kuwaiti (Arabs) Non-Kuwaiti (non-Arabs) Marital status Single Married Divorced/widowed Physical status Normal Overweight/obese Previous history of stroke Previous history of TIA Previous history of cardiac disease Previous history of atrial fibrillation Previous history of migraine Hypertension Diabetes Dyslipidemia Ever smoked Alcohol use Drug use Contraceptive drug use Family history of stroke (first-degree relatives)
1257 (100)
331 (26.3)
878 (69.8)
48 (3.8)
811 (64.5) 446 (35.5)
211 (63.7) 120 (36.3)
572 (65.1) 306 (34.9)
28 (58.3) 20 (41.7)
149 (11.9) 812 (64.6) 296 (23.5) 60.2 (13.1)
51 (15.4) 208 (62.8) 72 (21.8) 58.9 (13.8)
92 (10.5) 573 (65.3) 213 (24.3) 60.7 (12.8)
6 (12.5) 31 (64.6) 11 (22.9) 59.0 (12.8)
574 (45.7) 387 (30.6) 296 (23.5)
153 (46.2) 86 (26.0) 92 (27.8)
398 (45.3) 283 (32.2) 197 (22.4)
23 (47.9) 18 (37.5) 7 (14.6)
33 (2.6) 1181 (94.0) 43 (3.4)
11 (3.3) 307 (92.7) 13 (3.9)
20 (2.3) 831 (94.6) 27 (3.1)
2 (4.2) 43 (89.6) 3 (6.3)
605 (48.1) 652 (51.9) 428 (34.0) 164 (13.0) 437 (34.8) 136 (10.8) 9 (.7) 1017 (80.9) 817 (65.0) 337 (26.8) 435 (34.6) 44 (3.5) 2 (.2) 10 (2.3) 20 (1.6)
158 (47.7) 173 (52.3) 110 (33.2) 37 (11.2) 124 (37.5) 43 (13.0) 6 (1.8) 260 (78.5) 222 (67.1) 85 (25.7) 124 (37.5) 17 (5.1) 1 (.3) 3 (2.5) 5 (1.5)
420 (47.8) 458 (52.2) 304 (34.6) 121 (13.8) 285 (32.5) 67 (7.6) 3 (.3) 722 (82.2) 572 (65.1) 244 (27.8) 301 (34.3) 27 (3.1) 1 (.1) 7 (2.3) 15 (1.7)
27 (56.3) 21 (43.8) 14 (29.2) 6 (12.5) 28 (58.3) 26 (54.2) 0 (.0) 35 (72.9) 23 (47.9) 8 (16.7) 10 (20.8) 0 (.0) 0 (.0) 0 (.0) 0 (.0)
P value
.594*
.213*
.088† .075*
.505‡
.517*
Abbreviations: SD, standard deviation; TIA, transient ischemic attack. P values are generated using chi-square test, one-way analysis of variance (ANOVA), and Fisher’s exact test. *Chi-square test. †One-way ANOVA. ‡Fisher’s exact test.
.692* .485* .001* <.001* .041† .124* .034* .206* .072* .089* .512† .999† .648*
ARTICLE IN PRESS J.Y. AL-HASHEL ET AL.
4
Table 2. Treatment in patients by stroke subtype
Treatment
All
Large vessel n (%)
Small vessel n (%)
Cardioembolic n (%)
P value
Antiplatelet Anticoagulant Carotid endarterectomy Thrombolysis
1240 (98.6) 182 (14.5) 6 (.5) 5 (.4)
323 (97.6) 57 (17.2) 3 (.9) 3 (.9)
874 (99.5) 100 (11.4) 1 (.1) 1 (.1)
43 (89.6) 25 (52.1) 2 (4.2) 1 (2.1)
<.001* <.001* .003† .025†
Numbers may not add up to the total because of combinations of treatment. P values are generated using chi-square test and Fisher’s exact test. *Chi-square test. †Fisher’s exact test.
compared to patients with cardioembolic (20.8%) and smallartery ischemic strokes (34.3%). A family history of stroke in a first-degree relative was reported in 20 patients (1.6%), most of whom had small-vessel stroke (15 of 20). Only .4% of patients received thrombolysis as an acute treatment, most of whom had cardioembolic stroke, whereas most patients who had small-artery and largeartery ischemic strokes (98.6%) received antiplatelets, as shown in Table 2. Anticoagulation was prescribed in 14.5% of our cohort, primarily in patients with cardioembolic strokes (52.1%). Carotid endarterectomy was only performed in .5% (n = 6) of patients with cardioembolic stroke.
Stroke severity at onset, length of hospitalization, and outcome at discharge, and at 1 and 6 months followup, were outlined in Table 3. Neurological outcome at onset was considered severe in 50% and 46.2% of patients with cardioembolic and large-vessel ischemic strokes, respectively. Furthermore, patients with cardioembolic stroke had longer hospital stay. A total of 132 (10.5%) patients had complete recovery whereas 811 (64.5%) patients had improvement in their condition at discharge. Smallartery ischemic stroke was associated with better outcome at discharge when compared to other stroke subtypes (P < .001). A total of 56 (4.5%) patients died during their hospital stay.
Table 3. Stroke severity, length of hospitalization, and outcome in stroke subtype
Parameter Stroke severity (motor deficit at onset) Mild Moderate Severe Length of hospitalization, median (IQR) Outcome at discharge Recovered Improved Not improved Died Outcome at 1 month follow-up (n = 634) Recovered Improved Not improved Died Outcome at 6 months follow-up (n = 561) Recovered Improved Not improved Died
All
Large vessel n (%)
Small vessel n (%)
Cardioembolic n (%)
403 (32.1) 428 (34.0) 426 (33.9) 6 (4-11)
71 (21.5) 107 (32.3) 153 (46.2) 8 (4-17)
319 (36.3) 310 (35.3) 249 (28.4) 5 (4-9)
13 (27.1) 11 (22.9) 24 (50.0) 10 (6-25)
132 (10.5) 811 (64.5) 258 (20.5) 56 (4.5)
23 (6.9) 203 (61.3) 82 (24.8) 23 (6.9)
106 (12.1) 580 (66.1) 165 (18.8) 27 (3.1)
3 (6.3) 28 (58.3) 11 (22.9) 6 (12.5)
155 (24.4) 253 (39.9) 169 (26.7) 57 (9.0)
25 (15.2) 63 (38.2) 54 (32.7) 23 (13.9)
120 (27.4) 181 (41.3) 109 (24.9) 28 (6.4)
10 (32.3) 9 (29.0) 6 (19.4) 6 (19.4)
185 (33.0) 179 (31.9) 135 (24.1) 62 (11.1)
32 (23.2) 40 (29.0) 42 (30.4) 24 (17.4)
142 (35.9) 134 (33.8) 88 (22.2) 32 (8.1)
11 (40.7) 5 (18.5) 5 (18.5) 6 (22.2)
P value <.001*
<.001† <.001*
<.001*
.001†
Abbreviation: IQR, interquartile range. Data are column percentages. P values are generated using chi-square test and Fisher’s exact test. *Chi-square test. †Fisher’s exact test.
ARTICLE IN PRESS ISCHEMIC STROKE IN KUWAIT
5
Table 4. Outcome by demographic characteristics Age in years
Gender
Outcome
<45
45-70
>75
At discharge, n Recovered Improved Not improved Died P value At 1 month, n Recovered Improved Not improved Died P value At 6 months, n Recovered Improved Not improved Died P value
149 15 (10.1) 108 (72.5) 23 (15.4) 3 (2.0)
812 90 (11.1) 547 (67.4) 149 (18.3) 26 (3.2) <.001 398 108 (27.1) 175 (44.0) 89 (22.4) 26 (6.5) <.001 352 128 (36.4) 128 (36.4) 68 (19.3) 28 (8.0) <.001
296 27 (9.1) 156 (52.7) 86 (29.1) 27 (9.1)
51 20 (39.2) 17 (33.3) 11 (21.6) 3 (5.9) 37 23 (62.2) 6 (16.2) 5 (13.5) 3 (8.1)
185 27 (14.6) 61 (33.0) 69 (37.3) 28 (15.1) 172 34 (19.8) 45 (26.2) 62 (36.0) 31 (18.0)
Male
Female
811 446 90 (11.1) 42 (9.4) 539 (66.5) 272 (61.0) 151 (18.6) 107 (24.0) 31 (3.8) 25 (5.6) .042 370 264 98 (26.5) 57 (21.6) 145 (39.2) 108 (40.9) 96 (25.9) 73 (27.7) 31 (8.4) 26 (9.8) .539 319 242 114 (35.7) 71 (29.3) 98 (30.7) 81 (33.5) 75 (23.5) 60 (24.8) 32 (10.0) 30 (12.4) .419
Nationality
Kuwaiti 574 71 (12.4) 329 (57.3) 144 (25.1) 30 (5.2) 391 93 (23.8) 146 (37.3) 122 (31.2) 30 (7.7) 359 114 (31.8) 111 (30.9) 100 (27.9) 34 (9.5)
Non-Kuwaiti Arabs
Non-Kuwaiti non-Arabs
387 35 (9.0) 270 (69.8) 66 (17.1) 16 (4.1) <.001 160 39 (24.4) 73 (45.6) 32 (20.0) 16 (10.0) .043 142 42 (29.6) 54 (38.0) 29 (20.4) 17 (12.0) .003
296 26 (8.8) 212 (71.6) 48 (16.2) 10 (3.4) 83 23 (27.7) 34 (41.0) 15 (18.1) 11 (13.3) 60 29 (48.3) 14 (23.3) 6 (10.0) 11 (18.3)
Data are column percentages. P values are generated using chi-square test to compare between gender and outcome at discharge, and at 1 and 6 months follow-up.
The age, gender, and nationality of the patients showed a significant difference in the outcome at discharge (Table 4). Higher recovery or improvement rates were observed in the younger age group, men, and nonKuwaiti patients (Table 4). Similar findings were observed at 1 and 6 months follow-up according to age and nationality. However, the difference in gender was not significant. When the outcome of patients according to stroke severity at onset was assessed, there was a significant association between stroke severity and the outcome of patients at the 3 stages (Table 5). Worse neurological outcomes were observed among patients with severe stroke compared to mild or moderate groups. When the outcome by stroke severity and the stroke subtypes were stratified, the proportion of patients in the outcome was not significantly different among the subtypes in any of the stroke severity groups (Table 6).
Discussion Small-vessel ischemic stroke was the most prevalent (69.8%) subtype in our study, which was in line with previous reports from Kuwait (59.7%),5 Japan (56%),13 and Norway (75.2%).14 However, lower rates of large-vessel strokes were observed in our cohort (26.3%) when compared to reports in previous studies in Kuwait (46.5%),6 German (50%),15 and Latin America (32.4%).16 This discrepancy might be due to methodological differences, which
included different use of diagnostic criteria, and population studied. A high rate of small-vessel stroke in our study could be partly explained by the high prevalence of hypertension and diabetes in our population. However, other studies report no significant differences in risk factors associated with different stroke subtypes.17,18 We observed a male predominance (64.5%) in all subtypes of stroke, which was similarly reported in previous regional and international studies in Qatar (73%),19 Lebanon (60%),20 Italy (61.6%),21 Germany (57.6%),22 and Norway (69%).14 The mean age of stroke in our study was 60.2 years, which was similar to other reports (63.2 years in Lebanon,20 59 years in a prospective Arabian Gulf study).23 However, higher mean age of patients with stroke was reported in other international studies (65.9 in German,22 70.1 years in Norway,14 and 70.6 in Brooklyn, New York).24 Younger population and differences in genetic predisposition in the Middle East could partly explain this. Hypertension was the most common risk factor (80%), followed by diabetes (65%), cardiac disease (34.8%), smoking (34.6%), history of previous stroke (34%), and dyslipidemia (26.8%). This raises the importance of effective interventions for prevention and treatment of these risk factors among target population to reduce the burden of stroke. Our results are in agreement with previous Kuwait studies5,6,25 as well as other regional26,27 and international studies.21,22,28 However, few discrepancies are worth noting. Diabetes comprises 65% in this study, which
ARTICLE IN PRESS J.Y. AL-HASHEL ET AL.
6
Table 5. Outcome in stroke patients according to severity of stroke at onset
Outcome at discharge, n Recovered Improved Not improved Died P value Outcome at 1 month, n Recovered Improved Not improved Died P value Outcome at 6 months, n Recovered Improved Not improved Died P value
All
Mild
Moderate
Severe
1257 10.5 64.5 20.5 4.5
403 24.1 68.0 6.7 1.2
428 6.3 73.4 18.2 2.1
426 1.9 52.3 35.9 9.9
634 24.4 39.9 26.7 9.0
198 53.0 38.4 6.1 2.5
191 18.3 53.4 23.6 4.7
561 33.0 31.9 24.1 11.1
180 60.0 33.3 3.9 2.8
167 32.3 42.5 19.8 5.4
<.001 245 6.1 30.6 45.7 17.6 <.001 214 10.7 22.4 44.4 22.4 <.001
Data are column percentages. P values are generated using chi-square test to compare between severity of stroke at onset and outcome at discharge, and at 1 and 6 months follow-up.
Table 6. Outcome by stroke severity at onset and stroke subtypes Stroke severity at onset
Outcome At discharge, n Recovered Improved Not improved Died P value At 1 month, n Recovered Improved Not improved Died P value At 6 months, n Recovered Improved Not improved Died P value
Mild
Moderate
Severe
Stroke subtypes
Stroke subtypes
Stroke subtypes
Large vessel
Small vessel
Cardioembolic
71 22.5 73.2 2.8 1.4
319 24.8 66.5 7.5 1.3
13 15.4 76.9 7.7 .0
30 46.7 43.3 6.7 3.3
159 53.5 37.7 6.3 2.5
24 54.2 37.5 4.2 4.2
148 59.5 33.8 4.1 2.7
Large vessel
Small vessel
Cardioembolic
107 5.6 71.0 20.6 2.8
310 6.5 74.5 17.1 1.9
11 9.1 63.6 27.3 .0
9 66.7 33.3 .0 .0
45 20.0 46.7 26.7 6.7
140 16.4 57.1 22.1 4.3
8 87.5 12.5 .0 .0
39 35.9 30.8 25.6 7.7
123 30.1 47.2 17.9 4.9
.691
153
Small vessel
.7 49.0 37.9 12.4
249 2.8 55.0 35.3 6.8
6 50.0 16.7 33.3 .0
90 2.2 32.2 44.4 21.1
139 8.6 29.5 48.9 12.9
5 60.0 20.0 20.0 .0
75 6.7 25.3 41.3 26.7
125 13.6 20.8 48.0 17.6
.781
.948
.745
Large vessel
Data are column percentages. P values are generated using Fisher’s exact test.
24 .0 45.8 28.2 25.0 .061
.256
.398
Cardioembolic
16 6.3 31.3 25.0 37.5 .059 14 7.1 21.4 28.6 42.9 .209
ARTICLE IN PRESS ISCHEMIC STROKE IN KUWAIT
was much higher than in western studies as in German (28.5%),22 Norway (24.7%),14 and Italy (17%).21 This dissimilarity is most probably due to heritable causes and the more sedentary lifestyle in Kuwait. A higher frequency of previous stroke (34%) than in other countries was observed (28% in Italy21 and 22.8% in Germany)22; however, our results were lower than 42.9% in Brazil.28 These differences could be explained by genetic, environmental, or sociocultural factors. There was no association between the different subtypes of ischemic stroke and a previous attack in our study, which was similar to the German study.22 A history of TIA (13%) in our study was similar to the studies reported from Bahrain (11%)26 and Germany (12.7%).22 Nevertheless, no association was found between the different subtypes and previous history of TIA in our study, which was similar to Rochester study.29 On the contrary, a German study revealed a significant association between previous TIA and large-vessel stroke (20%).22 These differences could be attributed to the variation in case ascertainment and classification. Alcohol consumption was the least frequent risk factor in our cohort. This is likely because alcohol consumption is illegal in Kuwait. Significant differences were found among stroke subtypes; large-vessel stroke had more frequent diabetes and cardioembolic stroke had more frequent history of cardiac disease and atrial fibrillation. Hypertension and dyslipidemia were more prevalent in patients with small-vessel stroke; however, the difference was nonsignificant. In our cohort, diabetes was significantly associated with large-artery stroke subtype. It has been shown that diabetes was associated with increased level of coagulation factors and hyperinsulinemia associated with the development of large-vessel stroke.13 Small-vessel ischemic stroke in our cohort was significantly associated with dyslipidemia. Higher serum cholesterol level was shown to be associated with a higher prevalence of minor strokes.30 Thrombolysis was only used at a rate of .4%; this is similar to the Arabian Gulf study (.8%).24 The overall thrombolysis rate in our patients was below that of other international studies in Brazil (2.7%),31 Germany (3.6%),22 and Cleveland, USA (6.9%).32 Most patients with stroke in Kuwait were treated in public hospitals, where the thrombolysis protocols were not yet routinely available except in 2 hospitals at the time of conducting our study. Another obstacle to thrombolysis in Kuwait is the lack of stroke awareness, leading to delays in stroke triage. Patients with cardioembolic stroke were more likely to receive thrombolytic therapy in our cohort. Cardioembolic stroke was the most significant subtype associated with worse outcome, which was in agreement with previous studies.21,22 Favorable outcome at discharge was found to be significant with small-vessel ischemic stroke. On the other hand, mortality was significantly higher in cardioembolic stroke correlating with
7
disease severity. Our result was in agreement with previous western studies.20,29,33,34 There is no significant difference between men and women with regard to the outcome. As expected, an increase in age was significantly associated with poor outcome and mortality. Kuwaitis had worse outcomes and higher mortality rates than non-Kuwaitis at discharge. This could be explained by the differences in the demographics of expats who were young and in the working force. Our study had several limitations. First, it was retrospective in nature using chart review of patient’s records. Second, it was a hospital-based rather than a populationbased study. Third, the severity and outcome assessments were performed through examining motor deficits in both lower and upper limbs without the inclusion of the affection of activities of daily living, which are rather comprehensive assessment measures of functionality. This assessment was subjective and there was a high rate of intrarater variability among physicians. However, the strength of our result relies on being one of the largest cross-sectional studies conducted at the national level in the Middle East counties.
Conclusion The epidemiology of stroke in Kuwait is comparable to other regional and international areas. Small-artery ischemic stroke was the most common stroke subtype, and hypertension is the most common risk factor in Kuwait. There were differences in the prevalence of major risk factors among the stroke subtypes, demonstrating that knowledge of pathophysiology is essential for the proper management of these patients. Increasing age and embolic stroke subtypes were associated with an adverse outcome. There is an urgent need to design a stroke registration system in Kuwait for a better health planning. Preventive efforts should be directed at decreasing the number of new strokes by a better control of risk factors, particularly hypertension, diabetes, and atrial fibrillation in elderly patients, to decrease the burden of stroke. Our data may be helpful to the health authorities and may facilitate formulating new policies or recommendations with respect to the treatment of acute stroke focusing on the public awareness, modifiable risk factors, and the need for collaboration between neurology and vascular surgery specialists, along with reduction of any logistical hurdles to thrombolysis.
References 1. Kadojic D, Dikanovic M, Bitunjac M, et al. Epidemiology of stroke. Period Biol 2012;114:253-257. 2. Kim AS, Johnston SC. Global variation in the relative burden of stroke and ischemic heart disease. Circulation 2011;124:314-323. 3. Tran J, Mirzaei M, Anderson L, et al. The epidemiology of stroke in the Middle East and North Africa. J Neurol Sci 2010;295:38-40.
ARTICLE IN PRESS 8 4. Murray CJL, Lopez AD. The global burden of disease: a comprehensive assessment of morality and disability from diseases, injuries and risk factors in 1990 and projected to 2020. Boston: Harvard University Press, 1996. 5. Al-Shammri S, Shahid Z, Ghali A, et al. Risk factors, subtypes and outcome of ischaemic stroke in Kuwait—a hospital-based study. Med Princ Pract 2003;12:218-223. 6. Abdul-Ghaffar NU, El-Sonbaty MR, Abdul-Baky MSE, et al. Stroke in Kuwait: a three-year prospective study. Neuroepidemiology 1997;16:40-47. 7. WHO, World Health Organization. Cerebrovascular diseases: prevention, treatment and rehabilitation. World Health Organ Tech Rep Ser 1971;469:1-57. 8. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke 2011;42:227-276. 9. Jood K, Ladenvall C, Rosengren A, et al. Family history in ischemic stroke before 70 years of age: the Sahlgrenska Academy study on ischemic stroke. Stroke 2005;36:13831397. 10. Adams HP Jr, 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. 11. Kashinkunti MD, Mantri N, Dhananjaya MA. Retrospective study of stroke in young adults from tertiary care hospital. Scholars J Appl Med Sci 2013;1:506-510. 12. Bonita R, Beaglehole R. Recovery of motor function after stroke. Stroke 1988;19:1497-1500. 13. Tanizaki Y, Kiyohara Y, Kato I, et al. Incidence and risk factors for subtypes of cerebral infarction in a general population: the Hisayama study. Stroke 2000;31:2616-2622. 14. Altmann N, Thommessen B, Rønning OM, et al. Blood pressure differences between patients with lacunar and non lacunar infarcts. Brain Behav 2015;5:e00353. 15. Petty GW, Brown RD Jr, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke 1999;30:2513-2516. 16. Porcello Marrone LC, Diogo LP, de Oliveira FM, et al. Risk factors among stroke subtypes in Brazil. J Stroke Cerebrovasc Dis 2013;22:32-35. 17. Jackson C, Sudlow C. Comparing risks of death and recurrent vascular events between lacunar and nonlacunar infarction. Brain 2005;128:2507-2517. 18. Mohan KM, Crichton SL, Grieve AP, et al. Frequency and predictors for the risk of stroke recurrence up to 10 years after stroke: the South London stroke register. J Neurol Neurosurg Psychiatry 2009;80:1012-1018. 19. Khan FY, Yasin M, bu-Khattab M, et al. Stroke in Qatar: a first prospective hospital-based study of acute stroke. J Stroke Cerebrovasc Dis 2008;17:69-78.
J.Y. AL-HASHEL ET AL. 20. Lahoud N, Salameh P, Saleh N, et al. Prevalence of Lebanese stroke survivors: a comparative pilot study. J Epidemiol Glob Health 2015;doi:10.1016/j.jegh.2015.10.001; in press. 21. Corso G, Bottacchi E, Giardini G, et al. Epidemiology of stroke in Northern Italy: the Cerebrovascular Aosta Registry, 2004-2008. Neurol Sci 2013;34:1071-1081. 22. Grau AJ, Weimar C, Buggle F, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke 2001;32:2559-2566. 23. Deleu D, Inshasi J, Akhtar N, et al. Risk factors, management and outcome of subtypes of ischemic stroke: a stroke registry from the Arabian Gulf. J Neurol Sci 2011;300:142-147. 24. Sharma M, Helzner E, Sinert R, et al. Patient characteristics affecting stroke identification by emergency medical service providers in Brooklyn, New York. Intern Emerg Med 2016;11:229-236. 25. Ashkanani A, Hassan KA, Lamdhade S. Risk factors of stroke patients admitted to a general hospital in Kuwait. Int J Neurosci 2013;123:89-92. 26. Bahou Y, Hamid H, Raqab MZ. Ischemic stroke in Jordan 2000 to 2002: a two-year, hospital-based study. J Stroke Cerebrovasc Dis 2004;13:81-84. 27. Al-Jishi AA, Mohan PK. Profile of stroke in Bahrain. Neurosiences 2000;5:30-34. 28. Freitas de Carvalho JJ, Alves MB, Viana GAA, et al. Stroke epidemiology, patterns of management, and outcomes in Fortaleza, Brazil. A hospital-based multicenter prospective study. Stroke 2011;42:3341-3346. 29. Petty GW, Brown RD, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke 2000;31:1062-1068. 30. Olsen TS, Christensen RHB, Kammersgaard LP, et al. Higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality: ten-year follow-up of ischemic strokes in the Copenhagen stroke study. Stroke 2007;38:2646-2651. 31. Conforto AB, Paulo RB, Patroclo CB, et al. Stroke management in a university hospital in the largest South American City. Arq Neuropsiquiatr 2008;66:308311. 32. Katzan IL, Hammer MD, Hixson ED, et al. Utilization of intravenous tissue plasminogen activator for acute ischemic stroke. Arch Neurol 2004;61:346-350. 33. Lavados PM, Sacks C, Prina L, et al. Incidence, casefatality rate, and prognosis of ischaemic stroke subtypes in a predominantly Hispanic-Mestizo population in Iquique, Chile (PISCIS project): a community-based incidence study. Lancet Neurol 2007;6:140-148. 34. Lange MC, Cabral NL, Moro CHC, et al. Incidence and mortality of ischemic stroke subtypes in Joinville, Brazil: a population-based study. Arq Neuropsiquiatr 2015;73:648-654.