Stroke in Qatar: A First Prospective Hospital-based Study of Acute Stroke

Stroke in Qatar: A First Prospective Hospital-based Study of Acute Stroke Fahmi Yousef Khan, MD,* Mohammed Yasin, MBBS,* Mohammed AbuKhattab, MD,* A. Haleem El Hiday, MD,* Mehdi Errayes, MD,* Abdu Kaed Lotf, MD,x Abdulsalam Saif Ibrahim, MD,k Mushtak Talib Abbas, MD,† Issa Matar, MD,* Musaad Alsamawi, MD,x and Hassan Alhail, MD‡

Background: Stroke is a major cause of morbidity and mortality in Qatar. Objectives: The aim of our study was to determine types of strokes, the associated risk factors, clinical presentation, outcome, and time to hospital admission among Qatari and non-Qatari patients as well as young and nonyoung patients. Methods: We conducted a hospital-based prospective observational study including all patients admitted to Hamad Medical Corporation with first-ever stroke from September 15, 2004, to September 14, 2005. A stroke was defined according to World Health Organization criteria. Results: Stroke was confirmed in 270 patients of whom 217 (80.4%) had ischemic stroke and 53 (19.6%) had hemorrhagic stroke. Male patients predominated in all types of stroke. The main risk factors for stroke were hypertension and diabetes, whereas lacunar infarct was the most common subtype of ischemic stroke. Risk factor profiles were similar between Qatari and non-Qatari patients except for hypercholesterolemia, which was observed with a higher frequency in Qatari compared with non-Qatari patients with ischemic stroke. There were significant differences between the young and nonyoung patients with ischemic stroke with respect to risk factors, ejection fraction, ventricular wall-motion abnormalities, time to hospital admission, and outcome. Most patients arrived at the hospital more than 3 hours from stroke onset because of unawareness of stroke symptoms. The overall in-hospital mortality was 9.3%. Conclusions: Hypertension and diabetes mellitus were the main risk factors for stroke in Qatar, whereas lacunar infarct was the most common subtype. Significant differences between the young and nonyoung patients were observed with respect to risk factors, ejection fraction, ventricular wall-motion abnormalities, time to hospital admission, and outcome. Key Words: Hemorrhagic stroke—ischemic stroke—risk factors—stroke in Qatar. Ó 2008 by National Stroke Association

From the *Department of Medicine, †Intensive Care Department, and ‡Neurology, Hamad General Hospital, Doha, Qatar; and xDepartment of Medicine and kPulmonology and Intensive Care Department, Alkhor Hospital, Doha, Qatar. Received September 28, 2007; revision received November 18, 2007; accepted November 30, 2007. Address correspondence to Fahmi Yousef Khan, MD, Department of Medicine, Hamad General Hospital, PO Box 3050, Doha-Qatar. E-mail: [email protected]. 1052-3057/$—see front matter Ó 2008 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2007.11.004

Globally, stroke is the second leading cause of death.1 It accounts for 5.5 million deaths worldwide, equivalent to 9.6% of all deaths. Two thirds of these deaths occur in people living in developing countries and 40% of them are younger than 70 years.2 The global incidence of stroke will increase as the number of people older than 65 years is expected to increase from 390 million now to 800 million by 2025, reaching 10% of the total population. Although stroke is the leading cause of disability in the world, it is both preventable and treatable, and may be used as an indicator for the effect of public health initiatives. However, a consistent strategy for both treatment

Journal of Stroke and Cerebrovascular Diseases, Vol. 17, No. 2 (March-April), 2008: pp 69-78

69

F.Y. KHAN ET AL.

70

and prevention of stroke necessitates that reliable information on stroke occurrence is available to measure the current burden and to follow changes over time. Data on risk factors, clinical patterns, and outcome of stroke in Qatar are still incomplete. The aim of this study was to describe types of strokes, associated risk factors, clinical presentation, outcome, and time to hospital admission among Qatari and nonQatari patients as well as young and nonyoung patients, comparing the results with those of previously reported studies. The results of this study will be useful in strategic planning for stroke management in Qatar.

Methods This prospective observational hospital-based study was conducted at Hamad Medical Corporation (HMC), Qatar, which is a small country with an area of 11,521 km2 extending into the Persian Gulf from the eastern coast of Arabian Peninsula and has an estimated population size of 744,000 according to the 2004 census and is densely populated at the capital city of Doha (339,847). No official data are available, but it is estimated that the expatriate population constitutes about 60% of the total population. HMC serves as a tertiary referral center with many hospitals, covering all medical and surgical disciplines including 6 intensive care departments and one rehabilitation center for adults. Unfortunately there is no stroke department. All patients with stroke are admitted to the general medical ward, whereas critical cases are sent to the medical intensive care department. Free national health care service for all nationals is the cornerstone of the health care program. In addition, free medical service is provided for expatriates and visitors examined at the accident and emergency department, without requiring any referral from a health center. The patient population includes locals and expatriates mainly from other Arab countries and Asia who were admitted with suggested acute stroke between September 15, 2004, and September 14, 2005. Risk factors, presenting symptoms, site of lesion, and outcome were analyzed. Patients were included in the study if they had a confirmed eligible first-ever stroke as defined by World Health Organization (WHO).3 A stroke was defined according to WHO criteria as ‘‘rapidly developing clinical signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 hours or longer or leading to death, with no apparent cause other than vascular origin’’ (WHO 1989).3 The stroke was confirmed by clinical assessment, computed tomography (CT)/magnetic resonance (MR) imaging scan, or a combination of these. Patients with cerebral infarction, stroke in evolution, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH) that was documented either by CT scan or MR imaging were included in this study whereas cases

of transient ischemic attack (TIA), along with subdural and extradural hematomas, were excluded.

Case Ascertainment From September 2004 to September 2005, all patients with a first-ever stroke from the total study population were identified in a prospective way. To identify patients admitted to HMC, daily checks of hospital admissions, discharge records, and death certificates were made. There is no private health care for stroke in Qatar, but people with mild stroke or the very elderly in a nursing home (Al-Rumeilla Hospital) are not usually referred to the hospital. To ensure complete case ascertainment among the elderly, the geriatric hospital at Al-Rumeilla Hospital was checked for patients with stroke at regular intervals. To ensure inclusion of cases transferred to other hospitals in Qatar, the general practitioners in health centers and private hospitals were interviewed at regular intervals. Death certificates issued for people who died outside the hospital were also examined at regular intervals. For careful case ascertainment, all patients with stroke identified were interviewed and examined (interview the patients or relatives) by one of the authors and were monitored frequently until discharge. Clinical subtypes of ischemic stroke were rated according to the Oxfordshire Community Stroke Project criteria as total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), posterior circulation infarct (POCI), and lacunar infarct (LACI). Risk factors that were analyzed included hypertension (previous diagnosis, current treatment, or values . 160/ 90 mm Hg on at least two subsequent measurements); diabetes mellitus (previous diagnosis, current treatment with insulin or oral hypoglycemic medications, or fasting plasma glucose level , 7.0 mmol/L); smoking either cigarettes or hubble-bubble (current or former practice); hypercholesterolemia (fasting serum cholesterol $ 6.7 mmol/L); and hypertriglyceridemia (triglyceride $ 1.8 mmol/L). Other factors evaluated include atrial fibrillation (AF) (history of chronic AF, confirmed by at least one electrocardiogram, or presence of arrhythmia during hospitalization); previous myocardial infarction; TIA (an acute neurologic deficit of vascular origin lasting , 24 hours); and alcohol consumption. Alcohol consumption was regarded as a risk factor when a patient regularly drank alcohol at a level of greater than or equal to 30 g/ day or greater than or equal to 210 g/wk for more than 6 months before the stroke. All patients with ischemic stroke had echocardiography (transthoracic, transesophageal, or both) to rule out patent foramen ovale, intracardiac thrombi, and valvulopathies and to assess cardiac function. Assessment of carotid artery was performed by carotid duplex, MR angiography, or both. Patients with stroke, who had no obvious risk factors, were exposed to further investigations including: (1) MR

PROSPECTIVE STUDY OF ACUTE STROKE IN QATAR

71

Table 1. Stroke subtype distribution related to sex and age group Ischemic stroke

Stroke Age (y) 15-45 46-60 .60 Total

Hemorrhagic stroke

Total

M

F

Total (%)

M

F

Total (%)

N (%)

32 64 61 157

8 12 40 60

40 (18.4) 76 (35.1) 101 (46.5) 217 (80.4)

11 14 15 40

4 3 6 13

15 (28.3) 17 (32.1) 21 (39.6) 53 (19.6)

55 (20.4) 93 (34.4) 122 (45.2) 270 (100)

Abbreviations: F, female; M, male.

Data Analysis Statistical analysis was carried out using software (EpiInfo2000 CDC, Atlanta, GA). Quantitative variables are expressed as mean 6 SD. Student t test was used for continuous variables and Mann-Whitney U test if variables were not normally distributed. Fisher exact or Chi Square tests were used when appropriate to compare the data in Qatari versus non-Qatari and young versus nonyoung patients. Results were considered significant if the P value was less than .05.

Research Committee Approval The study was approved by the research committee at HMC. Informed consent was obtained from each participant before any interview or neurologic examination was conducted.

Stroke was confirmed in 270 patients (197 [73%] male and 73 [27%] female), with no significant sex-related difference in the relative frequency rates. The mean age was 57.1 6 13.3 years (range 17-93 years). Women had significantly higher mean age than did men (61.3 6 14.0 v 55.6 6 12.7, P 5 .002). In all, 101 (37.4%) of the patients were Qatari. Non-Qatari was formed by 169 (62.6%) patients, of whom 41 were Indian, 25 Pakistani, 18 Bengali, 14 Palestinian, 11 Philippino, 10 Egyptian, and the rest of other nationalities. A total of 217 (80.4%) patients had ischemic strokes, whereas 53 (19.6%) patients had hemorrhagic stroke. Table 1 compares age and sex groups. The most frequent time of stroke occurrence was between 6 AM and 12 PM; there was also a second peak between 12 PM and 6 PM (Figure 1). In all, 91 (33.7%) patients had their stroke on awakening. Average hospital stay was 21 days. Few treatment complications occurred. Four patients had aspiration pneumonia and two patients developed deep venous thrombosis. A total of 210 (77.7%) patients were discharged with neurologic deficit, whereas 35 (13%) patients were discharged without neurologic deficit. Total in-hospital mortality was 9.3% (25 of 270 patients), which was significantly higher in hemorrhagic stroke (16 of 53 [30.1%] compared with ischemic stroke (9 of 217, P , .001).

Hemorrhagic stroke A total of 53 patients were admitted with hemorrhagic stroke. The age was 56.9 6 13.4 years (range 26-93 years). Primary ICH was found in 88.7% (47 patients; 35 male and 12 female) and SAH occurred in 11.3% (6 patients; 120

Number of patients

angiography and/or 4-vessel angiography to define the cause of hemorrhagic stroke; or (2) protein C, protein S, homocysteine, factor V Leiden, anticardiolipin antibody, antithrombin III, and sickling test to define the cause of ischemic stroke. Stroke was labeled as undetermined origin if these evaluations failed to determine the cause. Data were collected in standard forms, including demographic characteristics, clinical presentation of acute stroke, medical causes and risk factors of acute stroke, coexisting medical conditions, drug history, laboratory tests, time interval between the onset of symptom to hospital admission of patients with suggested acute stroke, and final diagnosis. Time of symptom onset was ascertained from patients or relatives, along with demographic and basic clinical details. For patients who woke with symptoms, time of onset was taken as the time of waking. For those who were admitted unconscious after being found collapsed, time of onset was taken as the last time they were witnessed to be well. Time to admission was calculated using the arrival time routinely logged in emergency department records. We classify the outcome of stroke into death, survived without neurologic deficit, and survived with neurologic deficit.

100 80 60 40 20 0

12 MN6am

12 noon6pm

6pm12MN

Time

Results In all, 302 patients were admitted with a suggested diagnosis of acute stroke during the 1-year study period.

6am12 noon

total stroke

Figure 1.

Ischemic stroke

Hemorrhagic stroke

Circadian variations of stroke. MN, Midnight.

F.Y. KHAN ET AL.

72

Table 2. Clinical presentation, risk factors, echocardiographic findings, outcome, and hemorrhagic stroke subtype (N 5 53)

Variables M/F Age 6 SD Qatari/non-Qatari Presenting symptoms Headache Coma Convulsion Limb paralysis/weakness Speech deficit Gait imbalance Risk factors Hypertension Diabetes mellitus Previous TIA Smoking Hypercholesterolemia Chronic alcoholism Anticoagulation drugs Previous myocardial infarction Stroke subtypes (N 5 53) SAH (M/F) ICH (M/F) Site of ICH (N 5 47) Basal ganglion hemorrhage Cerebellar hemorrhage Thalamic hemorrhage Lobar hemorrhage Pontine hemorrhage In-hospital complications Deep vein thrombosis Outcome Discharged with neurologic deficit Discharged without neurologic deficit In-hospital mortality

Frequency (%) or mean 6 SD (range) 40/13 56.9 6 13.4 y (range 26-93 y) 15/38 36 (68) 24 (45.3) 5 (9.4) 29 (54.7) 19 (35.8) 4 (7.5) 42 (79.2) 14 (26.4) 9 (17) 6 (11.3) 6 (11.3) 6 (11.3) 6 (11.3) 4 (7.5)

5/1 (11.3) 35/12 (88.7) 9 (19.1) 4 (8.6) 7 (14.9) 18 (38.3) 9 (19.1)

Table 3. Comparison between young and non-young patients with hemorrhagic stroke

Variables Risk factors Hypertension Diabetes mellitus Previous TIA Smoking Hypercholesterolemia Chronic alcoholism Anticoagulation drugs Previous myocardial infarction Rupture aneurysm AV malformation Stroke subtypes SAH ICH Site of ICH Basal ganglion hemorrhage Cerebellar hemorrhage Thalamic hemorrhage Lobar hemorrhage Pontine hemorrhage In hospital complicaitons Deep vein thrombosis Outcome Discharged with neurological deficit Discharged without neurological deficit In hospital mortality

Young Non-young (. 45) (15-45) N 5 15 N 5 38 P value

10 (66.6) 32 (84.2) 2 (13.3) 12 (31.6) 1 (6.6) 8 (21) 1 (6.6) 5 (13) 0 6 (15.8) 2 (13.3) 4 (10.5) 1 (6.6) 5 (13) 0 4 (10.5) 2 (13.3) 2 (13.3)

0 0

5 (33.4) 1 (2.6) 10 (66.6) 37 (97.4) 1 (6.6)

8 (21)

ns ns ns ns ns ns ns ns ns ns .005 .005 ns

1 (6.6) 3 (7.9) 2 (13.3) 5 (13) 4 (26.6) 14 (36.8) 2 (13.3) 7 (18.4)

ns ns ns ns

1 (6.6)

ns

0

12 (80)

22 (58)

ns

1 (6.6)

2 (5.3)

ns

2 (13.3) 14 (36.8)

ns

1 (2) 34 (64)

Abbreviations: AV, arterio venous; ICH, intracerebral hemorrhage; ns, nonsignificant; SAH, subarachnoid hemorrhage; TIA, transient ischemic attack.

3 (5.7) 16 (30.2)

Abbreviations: F, female; ICH, intracerebral hemorrhage; M, male; SAH, subarachnoid hemorrhage; TIA, transient ischemic attack.

5 male and 1 female). Hypertension was the main risk factor for hemorrhagic stroke and occurred in 42 (79.2%) patients; of those, only 22 (41.5%) were under some form of antihypertensive treatment. SAH attributed to ruptured aneurysm was seen in two (3.7%) patients, whereas ICH caused by arteriovenous malformation was diagnosed in one (1.8%) woman. The main symptom was headache and was found in 37 (69.8%) patients. Regarding the main site of cerebral hemorrhage, lobar hemorrhage was diagnosed in 18 of the 47 (38.3%) patients with ICH. In-hospital mortality was 30.2% (16

of 53 patients), which was significantly higher in SAH (5 of 6 [83.3%]) compared with ICH (11 of 47 [23.4%]), (P 5.007). Table 2 shows clinical presentation, risk factors, echocardiographic findings, site of ICH, in-hospital complications, outcome, and hemorrhagic stroke subtypes. There were no significant differences between Qatari versus non-Qatari and young versus nonyoung patients with respect to risk factors, stroke subtypes, echocardiographic findings, complications, and outcome except for ICH and SAH. ICH was found with high frequency in nonyoung patients whereas SAH was predominant in young patients (Tables 3 and 4).

Ischemic stroke A total of 217 patients had ischemic stroke. The mean age was 57.2 6 13.3 years (range 17-91 years). In all, 157

PROSPECTIVE STUDY OF ACUTE STROKE IN QATAR

Table 4. Comparison between Qatari and non-Qatari patients with hemorrhagic stroke

Variables Risk factors Hypertension Diabetes mellitus Previous TIA Smoking Hypercholesterolemia Chronic alcoholism Anticoagulation drugs Previous myocardial infarction Rupture aneurysm AV malformation Stroke subtypes SAH 6 ICH 47 Site of ICH (N 5 47) Basal ganglion hemorrhage Cerebellar hemorrhage Thalamic hemorrhage Lobar hemorrhage 1 Pontine hemorrhage In hospital complicaitons Deep vein thrombosis Outcome Discharged with neurological deficit Discharged without neurological deficit In hospital mortality

73

Table 5. Clinical presentation, risk factors, echocardiographic findings, in-hospital complications, outcome, and ischemic stroke subtype

Qatari Non-Qatari N 5 15 N 5 38 P value Variables 11 (73.3) 31 (81.6) 4 (26.7) 10 (36.3) 3 (20) 6 (15.8) 2 (13.3) 4 (10.5) 2 (13.3) 4 (10.5) 2 (13.3) 4 (10.5) 3 (20) 3 (7.9) 0 4 (10.5) 0 1 (6.7)

2 (5.3) 1 (2.6)

1 (6.7) 5 (13.2) 14 (93.3) 33 (86.8) 2 (13.3)

ns ns ns ns ns ns ns ns ns ns ns ns

7 (18.4)

ns

3 (20) 1 (2.6) 2 (13.3) 5 (13.2) 5 (33.3) 13 (34.2) 2 (13.3) 7 (18.4)

ns ns ns ns

0

1 (2.6)

ns

9 (60)

25 (65.8)

ns

1 (6.7)

2 (5.3)

ns

5 (33.3) 11 (29)

ns

Abbreviations: AV, arterio venous; ICH, intracerebral hemorrhage; ns, nonsignificant; SAH, subarachnoid hemorrhage; TIA, transient ischemic attack.

(71.4%) patients were male and 60 (27.7%) were female. Qatari nationality comprised 86 (39.6%) patients, whereas non-Qatari involved 131 (61.4%) patients. Hypertension was the main risk factor for ischemic stroke; it was found in 160 (73.7%) patients. Of those, only 83 (38.2%) patients were under some form of antihypertensive treatment. Diabetes mellitus was found in 145 (66.8%) patients who had a mean hemoglobin A1c of 8.1% 6 1.2%; 94 (73.4%) patients were under treatment, of whom 67 (52.3%) had hemoglobin A1c greater than 7%. Hypercholesterolemia was found in 114 (52.5%) patient; 54 (47.3%) patients were under some form of treatment; mean low-density lipoprotein cholesterol was 4.2 6 0.22 mmol/L (164 6 8.7 mg/dL), and only 36 (31.5%) patients had low-density lipoprotein cholesterol levels less than 2.6 mmol/L (,100 mg/dL). For risk factors see Table 5. Regarding other risk factors, such as protein-C and -S

M/F Age 6 SD Qatari/non-Qatari Presenting symptoms Headache Coma Convulsion Limb paralysis/weakness Speech deficit Swallowing deficit Gait imbalance Incontinence Risk factors Hypertension Diabetes mellitus Hypercholesterolemia Smoking Alcohol intake Angina Previous AMI Atrial fibrillation Previous TIA Family history of stroke Oral contraceptives Antiphospholipid syndrome Sickle cell anemia Undetermined Echocardiographic findings EF% Ventricular wall-motion abnormalities Patent foramen ovale Carotid artery stenosis (.70%) Stroke subtypes TACS PACS LACS POCS Time to hospital admission Within 3 hr from stroke onset In-hospital complications Aspiration pneumonia Deep vein thrombosis Outcome Discharged with neurologic deficit Discharged without neurologic deficit In-hospital mortality

Frequency (%) or mean 6 SD (range) 157/60 57.2 6 13.3 y (17-91 y) 86/131 90 (41.4) 20 (9.2) 8 (3.6) 180 (83) 123 (56.6) 55 (25.3) 50 (23) 8 (3.6) 160 (73.7) 145 (66.8) 114 (52.5) 91 (42) 82 (37.7) 52 (24) 22 (10) 31 (14.2) 36 (16.5) 12 (5.5) 4 (1.8) 2 (1) 2 (1) 17 (7.8) 59 6 11.2 63 (29) 2 (1) 15 (7) 58 (26.7) 53 (24.4) 66 (30.4) 40 (18.4) 38 (17.5) 4 (1.8) 1 (0.5) 176 (81) 32 (14.8) 9 (4)

Abbreviations: AMI, acute myocardial infarction; EF, ejection fraction; F, female; LACS, lacunar stroke syndrome; M, male; PACS, partial anterior circulation stroke syndrome; POCS, posterior circulation stroke syndrome; TACS, total anterior circulation stroke syndrome; TIA, transient ischemic attack.

F.Y. KHAN ET AL.

74

Table 6. Comparison between young and non-young patients with ischemic stroke

Variables Risk factors Hypertension Diabetes mellitus Hypercholesterolemia Smoking Alcohol intake Angina Previous AMI A trial fibrillation Previous TIA Family history of stroke Oral contraceptives Antiphospholipid syndrome Sickle cell anemia Undetermined Echocardiographic findings EF% Ventricular wall motion abnormalities Patent foramen ovale Carotid artery stenosis (.70%) Stroke subtypes TACS PACS LACS POCS Time to hospital admission Within 3 hours from stroke onset In hospital complicaitons Aspiration pneumonia Deep vein thrombosis Outcome Discharged with neurological deficit Discharged without neurological deficit In hospital mortality

Young (15-45) N 5 40

Non-young .45 N 5 177

P value

16 (40) 13 (32.5) 11 (27.5) 11 (27.5) 9 (22.5) 0 0 0 0 0 3 (7.5) 2 (5) 2 (5) 17 (42.5)

144 (81.4) 132 (74.6) 103 (58) 80 (45) 73 (41.3) 52 (29.4) 22 (12.4) 31 (17.5) 36 (20.3) 12 (6.8) 1 (0.6) 0 0 0

,.001 ,.001 ,.001 ns .04 ,.001 .01 .009 .003 ns .02 .03 .03 ,.001

60 6 8.1 2 (5) 2 (5) 0

54 6 12.2 61 (34.5) 0 15 (8.5)

.03 ,.001 .03 ns

16 (40) 5 (12.5) 17 (42.5) 2 (5)

42 (23.7) 48 (27) 49 (27.7) 38 (21.5)

ns ns ns .02

18 (45)

20 (11.3)

,.001

1 (2.5) 1 (2.5)

3 (1.7) 0

ns ns

28 (70) 11 (27.5)

148 (83.6) 21 (11.8)

ns .02

1 (2.5)

8 (4.5)

ns

Abbreviations: AMI, acute myocardial infarction; EF, ejection fraction; LACS, lacunar stroke syndrome; ns, nonsignificant; PACS, partial anterior circulation stroke syndrome; POCS, posterior circulation stroke syndrome; TACS, total anterior circulation stroke syndrome; TIA, transient ischemic attack.

deficiency, homocystinemia, factor V Leiden, and antithrombin-III deficiency, none of the patients had these particular risk factors that are often seen in young stroke. All patients who had angina, previous myocardial infarction, or both were taking aspirin, clopidogrel, or both when they developed stroke. Severe carotid stenosis (.70%) was found in 15 (7%) patients, and all were older than 60 years. Although 177 (81.6%) patients had brain CT scan in the first 24 hours, stroke was confirmed only in 21 (12%) patients. The diagnoses were confirmed by further imaging studies, including repeated CT scan or MR imaging, within 2 weeks. The main symptom of ischemic stroke was limb paralysis/paresis, which was found in 180 (82.9%) patients. Among the 217 patients, only 38 (18%)

patients arrived to the hospital within 3 hours from stroke onset; none of our patients were treated with a thrombolytic. In-hospital mortality was 4.1% (9 of 217 patients). Table 5 shows clinical presentation, risk factors, echocardiographic findings, in-hospital complications, outcome, and ischemic stroke subtypes. In a comparison of risk factors between young and nonyoung patients, hypertension, diabetes, hypercholesterolemia, alcohol drinking, acute myocardial infarction, angina, TIA, and AF were more prevalent in nonyoung than the young subgroups, whereas oral contraceptives, antiphospholipid syndrome, sickle cell anemia, and undetermined hypertension were more prevalent in the young than nonyoung subgroups. Table 6 summarizes the differences between young and nonyoung subgroups.

PROSPECTIVE STUDY OF ACUTE STROKE IN QATAR

75

Table 7. Comparison between Qatari and non-Qatari patients with ischemic stroke Qatari N 5 86

Non-Qatari N 5 131

P value

62 (72) 62 (72) 54 (62.8) 40 (46.5) 28 (32.5) 21 (24.4) 9 (10.5) 14 (16.3) 14 (16.3) 5 (5.8) 1 (1.2) 1 (1.2) 1 (1.2) 5 (5.8)

98 (74.8) 83 (63.4) 60 (45.8) 51 (39) 54 (41.2) 31 (23.7) 13 (10) 17 (13) 22 (16.8) 7 (5.3) 3 (2.3) 1 (0.8) 1 (0.8) 12 (9)

ns ns .02 ns ns ns ns ns ns ns ns ns ns ns

55.6 6 11.7 20 (23.3) 1 (1.2) 5 (5.8)

54.3 6 10.2 43 (32.8) 1 (0.8) 10 (7.6)

ns ns ns ns

28 (32.5) 24 (28) 25 (29) 9 (10.5)

30 (23) 29 (22) 41 (31.3) 31 (23.7)

ns ns ns .02

16 (18.6)

22 (16.8)

ns

1 (1.2) 1 (1.2)

3 (2.3) 0

ns ns

69 (80.2) 15 (17.4) 2 (2.3)

107 (81.6) 17 (13) 7 (5.3)

ns ns ns

Variables Risk factors Hypertension Diabetes mellitus Hypercholesterolemia Smoking Alcohol intake Angina Previous AMI Atrial fibrillation Previous TIA Family history of stroke Oral contraceptives Antiphospholipid syndrome Sickle cell anemia Undetermined Echocardiographic findings EF% Ventricular wall motion abnormalities Patent foramen ovale Carotid artery stenosis (.70%) Stroke subtypes TACS PACS LACS POCS Time to hospital admission Within 3 hours from stroke onset In hospital complicaitons Aspiration pneumonia Deep vein thrombosis Outcome Discharged with neurological deficit Discharged without neurological deficit In hospital mortality

Abbreviations: AMI, acute myocardial infarction; EF, ejection fraction; LACS, lacunar stroke syndrome; ns, nonsignificant; PACS, partial anterior circulation stroke syndrome; POCS, posterior circulation stroke syndrome; TACS, total anterior circulation stroke syndrome; TIA, transient ischemic attack.

On the other hand, risk factor profiles were similar between Qatari and non-Qatari patients except for hypercholesterolemia, which was observed with a higher frequency in Qatari compared with non-Qatari patients. The comparison between Qatari and non-Qatari patients are summarized in Table 7.

Discussion Population-based studies provide the best estimation of stroke incidence.3,4 Moreover, stroke data banks and stroke registries provide the best information about cerebrovascular diseases.5,6 However, because these methods are not yet available nationwide in Qatar, the exact incidence and prevalence of stroke are not yet known. Despite these limitations some authors estimated the

overall incidence of stroke in Qatar to be 41/100,000 inhabitants/year.7 Stroke accounted for approximately 3.5% of admissions to the medical ward of HMC in Qatar during the period of the study, which was similar to that found in Saudi Arabia and other Arabic countries (e.g., Libya and Jordan).8-13 In comparison with a previous study,7 the annual number of patients admitted to our center with stroke increased from 214 to 270 patients, an increment that seems to be artificial because of the large expatriate influx to the country. In agreement with other reports, men predominated in all types of strokes irrespective of nationality.8-12 The peak frequency of stroke was above the sixth decade of life, and was less frequent in those younger than 45 years. This pattern was generally in line with those of other reports.14-16

76

The existence of a circadian rhythm of stroke has been established by the current study and other reports.17,18 The first peak occurred in the morning (6 AM-12 PM) for both infarcts and hemorrhages; a second peak was present in the afternoon and early evening (12 PM-6 PM). In our study, cerebral infarction accounted for 80.4% of cases, which was higher than that reported from some areas of Saudi Arabia8-10 and other countries19-22 but similar to that found in two hospital-based studies in a Saudi Arabia and Kuwait.11,23,24 ICH accounted for 17.4% of cases, whereas SAH accounted for 2.2% of cases, which was similar to that found in some areas of Saudi Arabia, Kuwait, and other countries11,23-25 but different from those reported in Bahrain, Libya, and other areas of Saudi Arabia.10,12,19 Untreated hypertension is highly prevalent and an important risk factor for hemorrhagic stroke worldwide.26 Previous studies27,28 and this study have shown that hypertension is a significant and independent risk factor for hemorrhagic stroke. It was estimated that among patients with hypertension, approximately one fourth of hemorrhagic strokes would be prevented if all patients with hypertension received treatment.26 The prevalence of lobar ICH in different studies has been reported to be 32% to 51%.29-33 In the current study lobar ICH accounted for 38.3% of cases, which falls within the above-mentioned range. Some authors34,35 suggested an association between hypertension and nonlobar (cerebellum, and brain stem) ICH, whereas another report suggested an association between smoking and lobar ICH.26 In our study lobar hemorrhage was significantly higher, despite high prevalence of hypertension among our patients, which suggests a multifactorial cause for lobar ICH. Consistent with many studies,8,11,12,32,33,36 other risk factors for hemorrhagic stroke in our study included previous diabetes mellitus, TIA, smoking, hypercholesterolemia, chronic alcoholism, anticoagulation drugs, and previous myocardial infarction. A significant relationship between low total cholesterol and the increased incidence of hemorrhagic stroke was found in recent studies from Korea and Japan37,38; such a relationship was not found in our study. Despite global attempts to improve its prognosis by medical or neurosurgical treatments, hemorrhagic stroke has a mortality of 39% to 50%, with half of the deaths occurring in the first 2 days.26,32,33,39 In our study, inhospital mortality for hemorrhagic stroke was 30.2%. Although there was no significant differences between Qatari and non-Qatari patients, this study has shown that ICH was more prevalent in nonyoung patients than young, whereas SAH was more prevalent in young patients than in nonyoung, in general agreement with data from many reports.25,33 Consistent with other reports,9-11,40-42 risk factors of ischemic stroke in our study included hypertension, hyperlipidemia, diabetes mellitus, ischemic heart disease,

F.Y. KHAN ET AL.

smoking, and AF. Most of our patients had more than one risk factor at the same time, with hypertension being the most frequent. In our study hypertension accounted for 73.7% of cases, which was similar to that reported in certain Arab countries13,43 but different from that reported in other Arab countries.10-12 In Qatar, hypertension and diabetes mellitus have high prevalence (25% and 15% of the population, respectively)44-46 and are often poorly controlled, which is noticed more in the non-Qatari group. Noncompliance of patients to medication and nonadherence to lifestyle measures such as dieting and exercise might have contributed to poor control of these two risk factors. This can in part explain the higher frequency of strokes among non-Qatari patients. In our study, 61.8% of patients who were hypertensive did not take their treatment. The role of inherited deficiency of coagulation inhibitors (protein-S, protein-C, and antithrombin-III deficiency) varies between studies. In the current study inherited deficiency of coagulation inhibitors had not been noted. However, in respect to other hematologic causes of stroke, positive lupus anticoagulant and anticardiolipin antibody result was found in two patients, whereas no patient was positive for factor V Leiden. The prevalence of patent foramen ovale in this study was low (0.9%), although many previous studies reported a high prevalence of patent foramen ovale.47-49 Worldwide, the prevalence of undetermined stroke has been reported to be 10.2% to 65.3%.8,9,12,13,19,22,50-52 In the current study the origin remained undetermined in 17 (7.8%) patients despite extensive causative workup. The differences in the distribution of stroke of undetermined origin among different reports may depend on the extent of the diagnostic workup. Concerning the subtypes of stroke, LACI was found in 30.4% of all cerebral infarction in Qatar, which was comparable to the incidence reported in patients in Saudi Arabia,8,9 Taiwan, and China52,53 but much higher than reports from other countries.11,19,22,54 High frequency of LACI in our study is probably explained by high frequency of hypertension among our patients.52,55 Although brain CT in the first 24 hours has limited value in the diagnosis of ischemic stroke (12%), it has great value in excluding hemorrhagic stroke or other conditions mimicking stroke. Current National Clinical Guidelines for Stroke (updated in 2004) from the Royal College of Physicians recommend brain imaging for all patients with suggested stroke within 24 hours of the event. Early imaging is considered to improve care and be cost-effective.56 The late presentation of our patients is of a major concern especially if thrombolytic therapy is to be considered. Among the 217 patients with ischemic stroke, 179 (82%) patients arrived at the hospital after 3 hours from stroke onset because of unawareness and/or late recognition of stroke. None of our patients were treated with thrombolytic therapy because the thrombolysis team stopped this project during the period of study for re-evaluation, as the

PROSPECTIVE STUDY OF ACUTE STROKE IN QATAR

previous experience in the outcome was disappointing. Thrombolysis with intravenous recombinant tissue plasminogen activator was given to 18 patients with acute ischemic stroke in Qatar in the period from January 2002 until the program was stopped in August 2004. With regard to complications, they were less frequently seen in our patients during their hospital stay, reflecting the standard of care provided in our hospital. In our study, in-hospital case-fatality rate was 9.3% of ischemic strokes, whereas in certain Arab countries and Taiwan it has been reported to be between 8% and 30%.11,23,52 Adequate data were not available in these studies to determine whether variations in treatments may have been responsible for variations in case-fatality rates, but possible explanations for the different fatality rates in these populations could be the diversity of stroke risk factors, comorbidities, and differences in stroke evaluation and treatment, or unique response to stroke therapies. The relatively good outcome in our patients may be a result of the higher rates of ischemic strokes that have high proportion of LACI.52,57,58 Although mortality in this study was low, a significant number of discharged patients remained disabled. The impact of this event on non-Qatari patients (especially young patients) is devastating because they lost their jobs and returned to their countries. According to Deleu et al,58 significant ethnic differences in age of occurrence, risk factor profile, and cardiovascular variables were observed in Qatar. In our study there were no significant differences between Qatari and nonQatari patients with respect to risk factors except for hypercholesterolemia, which was observed with a higher frequency in Qatari patients compared with non-Qatari, indicating the considerable effect of dietary habits. However, posterior circulation stroke syndrome was observed more in non-Qatari than in Qatari patients. On the other hand, significant differences between the young and nonyoung patients were observed with respect to number of risk factors, ejection fraction, ventricular wall-motion abnormalities, and outcome. Moreover, the number of young patients who arrived within 3 hours of stroke onset was significantly larger than those in nonyoung patients. We think the differences observed in age, sex distribution, stroke risk factors, and subtypes between Qatari and non-Qatari patients is most likely a reflection of the demographic structure existing in Qatar rather than ethnic variation; whereas the differences observed in number of risk factors, ventricular wall-motion abnormalities, time to hospital admission, and outcome between young and nonyoung patients is most likely a reflection of physiologic and behavioral characteristics of each subgroup. Several limitations have been noted in our study. The study was hospital based rather than population based, but having our center as the only referral center is probably reflecting the actual burden of stroke in the country. In considering the risk factors, the interplay of different factors, especially obesity, should be considered for further

77

studies. In addition, the degree of the neurologic deficit on discharge would have been better evaluated based on functional status score, but for practical reasons it was categorized into those with and those without neurologic deficit. For the outcome at 1 year, no follow-up was conducted in our patients because of technical difficulties. In conclusion, this study has shown that stroke is a major cause of morbidity and mortality in Qatar. To reduce morbidity and mortality caused by stroke we recommend the following: (1) prevention of primary risk factors, hypertension, and diabetes mellitus; (2) education targeting public and primary health care workers for early referral of strokes to stroke departments; (3) addition of thrombolysis in the golden hours; (4) lifestyle modifications in a population at increased risk; (5) secondary prevention of recurrence for both Qatari and non-Qatari patients; (6) more nursing homes and rehabilitation centers to reduce burden on tertiary hospitals; and (7) establishment of stroke data banks and national stroke registries to provide further information on the epidemiology of stroke in Qatar.

References 1. Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: Global burden of disease study. Lancet 1997;349:1269-1276. 2. World Health Organization. The world health report: Reducing risks, promoting healthy life. World Health Organization; 2002. 3. Bonita R, Stewart AW, Bewart AW, et al. International trends in stroke mortality: 1970-1985. Stroke 1990; 21:989-992. 4. Sudlow CLM, Warlow CP. Comparing stroke incidence worldwide: What makes studies comparable? Stroke 1996;27:550-558. 5. Kunitz SC, Gross CR, Heyman A, et al. The pilot stroke data bank: Definition, design, and data. Stroke 1984; 15:740-746. 6. Mohr JP, Caplan LR, Melski JW. The Harvard cooperative stroke registry: A prospective registry. Neurology 1978; 28:754-762. 7. Hamad A, Hamad A, Sokrab TE, et al. Stroke in Qatar: A one-year, hospital-based study. J Stroke Cerebrovasc Dis 2001;10:236-241. 8. Al-Rajeh S, Larbi E, Bademosi O, et al. Stroke in a tertiary hospital in Saudi Arabia: A study of 372 cases. Eur Neurol 1991;31:251-256. 9. Al-Rajeh S, Awada A, Niazi G, et al. Stroke in a Saudi Arabian National Guard community: Analysis of 500 consecutive cases from a population-based hospital. Stroke 1993;24:1635-1639. 10. Al-Rajeh S, Larabi EB, Bademosi O, et al. Stoke register: Experience from the eastern province of Saudi Arabia. Cerebrovasc Dis 1998;8:86-89. 11. Qari FA. Profile of stroke in a teaching university hospital in the western region. Neurosciences 2001;6:38-41. 12. El-Zunni S, Ahmed M, Prakash P, et al. Stroke: Incidence and pattern in Benghazi, Libya. Ann Saudi Med 1995; 5:367-369. 13. Bahou Y, Hamid H, Hadidi A. Ischemic stroke in Jordan: A 2-year hospital-based study of subtypes and risk factors. East Mediterr Health J 2004;10:138-146. 14. Warlow CP. Epidemiology of stroke. Lancet 1998; 352(suppl):1-4.

F.Y. KHAN ET AL.

78 15. Poungvarin N. Stroke in the developing world. Lancet 1998;332(suppl):19-22. 16. Awada A, Al Rajeh S. The Saudi stroke data bank: Analysis of the first 1000 cases. Acta Neurol Scand 1999;100:265-269. 17. Elliott WJ. Circadian variation in the timing of stroke onset: A meta-analysis. Stroke 1998;29:992-996. 18. Lago A, Geffner D, Tembl J, et al. Circadian variation in acute ischemic stroke: A hospital-based study. Stroke 1998;29:1873-1875. 19. Al Jishi A, Mohan PK. Profile of stroke in Bahrain. Neurosciences 2000;5:30-34. 20. Hu HH, Sheng WY, Chu FL, et al. Incidence of stroke in Taiwan. Stroke 1992;23:1237-1241. 21. Whisnant JP, Fitzgibbons JP, Kurland LT, et al. Natural history of stroke in Rochester, Minnesota, 1945 through 1954. Stroke 1971;2:11-22. 22. Yatsu FM, Becker C, McLeroy KR, et al. Community hospital-based stroke programs: North Carolina, Oregon, and New York. Stroke 1986;17:276-284. 23. El Sayed MM, Adeuja OG, El-Nahrawy E, et al. Characteristics of stroke in Hofuf, Saudi Arabia. Ann Saudi Med 1999;19:27-31. 24. Abdul-Ghaffar NU, el-Sonbaty MR, el-Din AbdulBaky MS, et al. Stroke in Kuwait: A three-year prospective study. Neuroepidemiology 1997;16:40-47. 25. Broderick JP, Brott T, Tomsick T, et al. Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg 1993;78:188-191. 26. Woo D, Haverbusch M, Sekar P, et al. Effect of untreated hypertension on hemorrhagic stroke. Stroke 2004; 35:1703-1708. 27. Woo D, Sauerbeck LR, Kissela BM, et al. Genetic and environmental risk factors for intracerebral hemorrhage: Preliminary results of a population-based study. Stroke 2002;33:1190-1196. 28. Kissela BM, Sauerbeck L, Woo D, et al. Subarachnoid hemorrhage: A preventable disease with a heritable component. Stroke 2002;33:1321-1326. 29. Boonyakarnkul S, Dennis M, Sandercock P, et al. Primary intracerebral hemorrhage in the Oxfordshire community stroke project, 1: Incidence, clinical features and causes. Cerebrovasc Dis 1993;3:343-349. 30. Anderson CS, Chakera TM, Stewart-Wynne E, et al. Spectrum of primary intracerebral hemorrhage in Perth, Western Australia, 1989-90: Incidence and outcome. J Neurol Neurosurg Psychiatry 1994;57:936-940. 31. Broderick J, Brott T, Tomsick T, et al. Lobar hemorrhage in the elderly: The undiminishing importance of hypertension. Stroke 1993;24:49-51. 32. Fogelholm R, Nuutila M, Vuorela AL. Primary intracerebral hemorrhage in the Jyva¨skla¨ region, central Finland, 1985-9: Incidence, case fatality rate, and functional outcome. J Neurol Neurosurg Psychiatry 1992;55:546-552. 33. Nilsson OG, Lindgren A, Sta˚hl N, et al. Incidence of intracerebral and subarachnoid hemorrhage in southern Sweden. J Neurol Neurosurg Psychiatry 2000;69:601-607. 34. Broderick J. Intracerebral hemorrhage. In: Gorelick P, Alter M, eds. Handbook of neuroepidemiology. New York: Marcel Dekker Inc; 1994:141-167. 35. Challa V, Moody D, Bell M. The Charcot-Bouchard aneurysm controversy: Impact of a new histologic technique. J Neuropathol Exp Neurol 1992;51:264-271. 36. Feldmann E, Broderick JP, Kernan WN, et al. Major risk factors for intracerebral hemorrhage in the young are modifiable. Stroke 2005;36:1881-1885. 37. Okumura K, Iseki K, Wakugami K, et al. Low serum cholesterol as a risk factor for hemorrhagic stroke in men:

38.

39.

40. 41. 42.

43.

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56. 57.

58.

A community-based mass screening in Okinawa, Japan. Jpn Circ J 1999;63:53-58. Suh I, Jee SH, Kim HC, et al. Low serum cholesterol and hemorrhagic stroke in men: Korea Medical Insurance Corporation study. Lancet 2001;357:922-925. Broderick JP, Viscoli CM, Brott T, et al. Major risk factors for aneurysmal subarachnoid hemorrhage in the young are modifiable. Stroke 2003;34:1375-1381. Dyken M, Wolf PA, Bernette JHM, et al. Risk factors in stroke. Stroke 1984;15:1105-1111. Wolf PA, Kannel WB, Verter J. Current status of risk factors for stroke. Neurol Clin 1983;1:317-343. Sandercock PA, Warlow CP, Jones LN, et al. Predisposing factors for cerebral infarction: The Oxfordshire community stroke project. BMJ 1989;298:75-80. Al-Shammri S, Shahid Z, Ghali A, et al. Risk factors, subtypes and outcome of ischemic stroke in Kuwait–a hospital-based study. Med Princ Pract 2003;12:218-223. Bener A. Is hypertension a predictor risk factor for acute myocardial infarction? Nephrol Hypertens 2004; 10:77-81. Bener A, Al Suwaidi J, El-Menyar A, et al. The effect of hypertension as a predictor of risk for congestive heart failure patients over a 10-year period in a newly developed country. Blood Press 2004;13:41-46. Bener A, Al Suwaidi J, Al Jaber K, et al. The epidemiology of hypertension and its associated risk factors in the Qatari population. J Hum Hypertens 2004; 18:529-530. Lechat P, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988;318:1148-1152. Di Tullio M, Sacco RL, Gopal A, et al. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992;117:461-465. Homma S, Di Tullio MR, Sacco RL, et al. Characteristics of patent foramen ovale associated with cryptogenic stroke: A biplane transesophageal echocardiographic study. Stroke 1994;25:582-586. Sagui E, M’Baye PS, Dubecq CBA, et al. Ischemic and hemorrhagic strokes in Dakar, Senegal: A hospital-based study. Stroke 2005;36:1844-1847. Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undetermined cause: The NINCDS stroke data bank. Ann Neurol 1989;25:382-390. Yip PK, Jeng JS, Lee TK, et al. Subtypes of ischemic stroke: A hospital-based stroke registry in Taiwan (SCAN-IV). Stroke 1997;28:2507-2512. Davis LE, Xie JG, Zou AH, et al. Deep cerebral infarcts in the People’s Republic of China. Stroke 1990;21: 394-396. Chambers BR, Donnan GA, Baldin PF. Patterns of stroke: An analysis of the first 700 consecutive admissions to the Austin Hospital stroke unit. Aust N Z J Med 1983; 13:57-64. Sacco SE, Whisnant JP, Broderick JP, et al. Epidemiological characteristics of lacunar infarcts in a population. Stroke 1991;22:1236-1241. Wardlaw JM, Farrall AJ. Diagnosis of stroke on neuroimaging. BMJ 2004;328:655-656. Ward G, Jamrozik K, Stewart-Wynne W. Incidence and outcome of cerebrovascular disease in Perth, western Australia. Stroke 1988;19:1501-1506. Deleu D, Hamad AA, Kamran S, et al. Ethnic variations in risk factor profile, pattern and recurrence of noncardioembolic ischemic stroke. Arch Med Res 2006;37: 655-662.