Study protocol: asymptomatic intracranial atherosclerotic disease in pakistanis.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is the most frequent subtype of ischemic stroke globally. It is important to describe the determinants of early ICAD as a strategy to prevent strokes from clinically evident and progressive ICAD. Our objective is to report the determinants of asymptomatic ICAD by linking the presence or absence of ICAD on magnetic resonance angiogram (MRA) with detailed risk assessment in asymptomatic adults. METHODS: This is an observational cross-sectional analytical study. We plan to recruit 200 adult participants from the radiology departments of two tertiary care centers of Karachi, Pakistan. The participants will first be screened for the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS). QVSFS negative will be participants will be eligible. After written informed consent, participants will undergo detailed medical, sociodemographic, lifestyle, and anthropometric evaluation by a detailed interview. They will, in addition, undergo MRA to study the presence, degree, and distribution of asymptomatic ICAD. All MRA scans will be reviewed centrally by vascular neurologists blinded to clinical information. These images would be reviewed on DICOM Viewer 3.0 used for calculating the degree of stenosis using Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) study defined criteria employing electronic calipers. A sample size of 200 will achieve 80% power for detecting a minimum difference of 20% in the prevalence of exposure factors (medical and lifestyle) between asymptomatic ICAD positive and ICAD negative persons. This study will generate regional data on risks for ICAD development and prevention in a high-risk susceptible population. Study ID: NCT02072876.

Clinical, lifestyle, socioeconomic determinants and rate of asymptomatic intracranial atherosclerosis in stroke free Pakistanis.

BACKGROUND: Intracranial Atherosclerotic Disease (ICAD) is the most frequent etiology of stroke with high prevalence among Asians. Despite this, early determinants of ICAD have not been described from this region. METHODS: The study is an analytical prospective cross-sectional study of 200 adults from Radiology Departments of two diagnostic centers in Karachi. Eligible participants confirmed the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS) and underwent an interview covering medical, socio demographic, lifestyle and anthropometric evaluation using locally validated and standardized definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect ICAD using the criterion used in the Warfarin-Aspirin Symptomatic Intracranial Disease study. The risk factors associated with asymptomatic ICAD are reported along with prevalence ratios. RESULTS: Of the 200 participants, ICAD was found in 34.5% (n = 69) of the participants. Mean age was 37.1 (S.D 15.1) years with 62% younger than 45 years. Self-reported hypertension was found in 26.5% subjects, diabetes in 9%, dyslipidemia in 5% and depression in 60%. Smokeless tobacco (Adjusted PR 3.27 (1.07-6.05)), Western diet, high socioeconomic status (Adjusted PR 2.26 (1.99-5.62)) and dyslipidemia (Adjusted PR 1.88 (1.25-2.21)) had significant associations with ICAD after multivariable analysis. Age, gender, diabetes, hypertension, depression and physical activity did not have a significant association. CONCLUSION: ICAD was found on MRI in one in three asymptomatic Pakistanis and was associated with modifiable risks. Initiatives targeting primary prevention may be able to decrease the burden of disease caused by stroke due to ICAD. STUDY REGISTRATION NUMBER: NCT02072876 2/25/2014.

Distribution, Severity and Radiologic Features of Intracranial Stenosis in Asymptomatic Pakistanis.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is the most common ischemic stroke subtype globally. It accounts for 30-50% of all ischemic strokes in Asians. AIMS: The aim of the study is to report the frequency of asymptomatic ICAD and its associated Magnetic Resonance Imaging (MRI) findings. METHODS: 200 adult participants were recruited from the Radiology Departments of two major diagnostic centers in Karachi. Eligible participants were confirmed for the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS). QVSFS negative subjects underwent MRI on a 1.5 Tesla scanner. Images were centrally reviewed on Di com Viewer 3.0 with electronic calipers to calculate the degree of ICAD. RESULTS: Mean age of subjects was 37.1 years (S.D 15.1) with 50.5% men (n=101) and 49.5% women (n=99). Asymptomatic ICAD was found in 34.5% (n=69) subjects. Of the 3800 intracranial arteries studied, 2.2% (n=88) had biological disease. 20.5% (n=18) of these vessels had atherosclerotic irregularities, 43.2% (n=38) had mild stenos is, 11.4% (n=10) had moderate stenos is, 5.7% (n=5) had severe stenos is while 19.3% (n=17) were completely occluded. The posterior cerebral artery (42% of stenosed arteries, n=37) was most affected. 23.5% (n=47) of subjects had peri-ventricular lucencies, 10.5% (n=21) had brain atrophy while 3.5% (n=7) had silent brain infarcts. There was a significant association between asymptomatic ICAD and peri ventricular lucencies (PR 1.59; 95% CI 1.35-1.99). CONCLUSION: Asymptomatic ICAD is common in young Pakistanis, with no gender predilection; it preferentially affects the posterior circulation. Silent infarcts are rare compared to peri ventricular lucencies and atrophy.

Left atrial volumes and associated stroke subtypes.

BACKGROUND: Cardio embolism and cerebrovascular atherosclerosis are two major mechanisms of stroke. Studies investigating associations between advanced echocardiographic parameters and stroke mechanisms are limited. METHODS: This study is a standardized review of 633 patients admitted to the stroke service of a tertiary care hospital following a standardized stroke investigation and management pathway. Stroke subtypes were characterized using the Causative Classification System, using the hospitals online radiologic archival system with CCS certified stroke investigators. Patients with two mechanisms were excluded. RESULTS: Patients with cardioembolic stroke had a higher proportion of atrial fibrillation (p < 0.001), acute myocardial infarction (p < 0.001) and ischemic heart disease (p < 0.001). On electrocardiogram (ECG) and transthoracic Echo (TTE), patients with cardioembolic stroke had a greater atrial fibrillation (p < .00), left ventricular thrombus (p < .00), left ventricular ejection fraction <30% (p < .00) and global hypokinesia (p < .00) Patients with cardioembolic stroke had higher mean left atrial volume indices (LAVi) (p < 0.001), mean left ventricular mass indices (LVMi) (p < 0.05) and mean left atrial diameters (LAD) (p < 0.05). At LAVi of 29-33 ml/m2, the risk of atherothrombotic stroke increased. The risk of cardioembolic stroke increased with LAVi of 34 ml/m2 and above. CONCLUSION: Left atrial volume indices may be linked to specific stroke phenotype. At mild increases in left atrial dimensions, the risks of atherosclerotic stroke are high, and probably reflect hypertension as the unifying mechanism. Further increases in left atrial dimensions shifts the risk towards cardioembolic stroke.

The burden of stroke and transient ischemic attack in Pakistan: a community-based prevalence study.

BACKGROUND: The burden of cerebrovascular disease in developing countries is rising sharply. The prevalence of established risk factors of stroke is exceptionally high in Pakistan. However, there is limited data on the burden of stroke and transient ischemic attack (TIA) in South Asia. We report the first such study conducted in an urban slum of Karachi, Pakistan. METHODS: Individuals 35 years of age or older were invited for participation in this investigation through simple random sampling. A structured face-to-face interview was conducted using a pre-tested stroke symptom questionnaire in each participant to screen for past stroke or TIA followed by neurological examination of suspected cases. Anthropometric measurements and random blood glucose levels were recorded. Multivariable logistic regression was used to determine the association of vascular risk factors with prevalence of stroke. RESULTS: Five hundred and forty five individuals (49.4% females) participated in the study with a response rate of 90.8%. One hundred and four individuals (19.1%) were observed to have a prior stroke while TIA was found in 53 individuals (9.7%). Overall, 119 individuals (21.8% with 66.4% females) had stroke and/or TIA. Female gender, old age, raised random blood glucose level and use of chewable tobacco were significantly associated with the prevalence of cerebrovascular disease. CONCLUSION: This is the first study demonstrating an alarmingly high life-time prevalence of cerebrovascular disease in Pakistan. Individual and public health interventions in Pakistan to increase awareness about stroke, its prevention and therapy are warranted.