Ayeesha Kamran Kamal

Cerebral venous thrombosis: a descriptive multicenter study of patients in Pakistan and Middle East

Background and Purpose— The natural history, causative factors, and outcomes of patients with cerebral venous thrombosis from Asia and Middle East have not been well described. This descriptive multicenter study describes the results for cerebral venous thrombosis patients in South Asia and the Middle East. Methods— The retrospective and prospective data of patients with radiologically confirmed cerebral venous thrombosis were collected from 4 centers located in Pakistan and United Arab Emirates. The demographic, clinical, radiological, and outcome data were recorded and analyzed. Primary outcome was death or dependency (modified Rankin score >2) at the time of hospital discharge. Results— This study included 109 patients with cerebral venous thrombosis; the presenting features most commonly being observed were headache (81%), focal motor deficits (45%), seizures (39%), and mental status changes (37%). Important predisposing factors included systemic and central nervous system infection (18%), postpartum state (17%), hyperhomocystinemia (9%), genetic thrombophilia (5%), and oral contraceptive pill use (3%). Ninety-six (67%) patients received therapeutic anticoagulation. Seven patients died and 43 had poor outcome at discharge. Focal motor deficits (OR, 2.93; 95% CI, 1.2–7.5; P=0.018) and hemorrhagic infarctions (OR, 2.81; 95% CI, 1.04–7.85; P=0.041) were independent predictors of unfavorable outcome at discharge. Hemorrhagic infarction was the most significant factor of long-term unfavorable outcome (OR, 5.87; 95% CI, 1.49–23.02; P=0.011). Conclusions— Infections and postpartum state were the most common predisposing factors for cerebral venous thrombosis in this cohort. Most patients (67%) were treated with anticoagulation therapy. Almost 50% of patients were dead or disabled at discharge.

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

BackgroundThe 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.MethodsIndividuals 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.ResultsFive 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.ConclusionThis 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.

Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study

BACKGROUND Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. OBJECTIVES Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF). METHODS This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. RESULTS Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations. CONCLUSIONS Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions.

Are Myocardial Infarction–Associated Single-Nucleotide Polymorphisms Associated With Ischemic Stroke?

Background and Purpose— Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Methods— Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific &bgr;s and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results— Despite having power to detect odds ratio of 1.09–1.14 for overall IS and 1.20–1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions— Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.

Functional, cognitive and psychological outcomes, and recurrent vascular events in Pakistani stroke survivors: a cross sectional study

BackgroundThere is little direct data describing the outcomes and recurrent vascular morbidity and mortality of stroke survivors from low and middle income countries like Pakistan. This study describes functional, cognitive and vascular morbidity and mortality of Pakistani stroke survivors discharged from a dedicated stroke center within a nonprofit tertiary care hospital based in a multiethnic city with a population of more than 20 million.MethodsPatients with stroke, aged > 18 years, discharged alive from a tertiary care centre were contacted via telephone and a cross sectional study was conducted. All the discharges were contacted. Patients or their legal surrogate were interviewed regarding functional, cognitive and psychological outcomes and recurrent vascular events using standardized, pretested and translated scales. A verbal autopsy was carried out for patients who had died after discharge. Stroke subtype and risk factors data was collected from the medical records. Subdural hemorrhages, traumatic ICH, subarachnoid hemorrhage, iatrogenic stroke within hospital and all other diagnoses that presented like stroke but were subsequently found not to have stroke were also excluded. Composites were created for functional outcome variable and depression. Data were analyzed using logistic regression.Results309 subjects were interviewed at a median of 5.5 months post discharge. 12.3% of the patients had died, mostly from recurrent vascular events or stroke complications. Poor functional outcome defined as Modified Rankin Score (mRS) of > 2 and a Barthel Index (BI) score of < 90 was seen in 51%. Older age (Adj-OR-2.1, p = 0.01), moderate to severe dementia (Adj-OR-19.1, p < 0.001), Diabetes (Adj-OR-2.1, p = 0.02) and multiple post stroke complications (Adj-OR-3.6, p = 0.02) were independent predictors of poor functional outcome. Cognitive outcomes were poor in 42% and predictors of moderate to severe dementia were depression (Adj-OR-6.86, p < 0.001), multiple post stroke complications (Adj-OR-4.58, p = 0.01), presence of bed sores (Adj-OR-17.13, p = 0.01) and history of atrial fibrillation (Adj-OR-5.12, p < 0.001).ConclusionsPakistani stroke survivors have poor outcomes in the community, mostly from preventable complications. Despite advanced disability, the principal caretakers were family rarely supported by health care personnel, highlighting the need to develop robust home care support for caregivers in these challenging resource poor settings.

Frequency and Outcome of Carotid Atheromatous Disease in Patients With Stroke in Pakistan

Background and Purpose— Limited data exist on the frequency and outcome of carotid artery disease in Pakistan. Such information would help guide the usefulness of screening for the condition in this low-middle income health care setting. Methods— A prospective, descriptive study was conducted among 3 large teaching hospitals in Karachi, Pakistan. Patients referred for carotid Doppler ultrasound examination were included if they had experienced a stroke or TIA within the previous month. The severity and morphology of carotid disease were characterized by trained technicians using standardized criteria. Demographic and risk factor data were collected at baseline, and the outcome of patients was assessed at least 6 months later. Results— A total of 672 patients underwent bilateral carotid Doppler ultrasound (1344 carotid examinations). The findings revealed 0% to 50% stenosis in 526 (78%), 51% to 69% stenosis in 57 (8%), 70% to 99% stenosis in 82 (12%), and total occlusion in 7 patients (1%). Potentially surgically correctable disease, defined as 70% to 99% carotid artery stenosis, was present in only 79 (12%) patients, of whom 47 (60%) were ipsilateral symptomatic, 15 (20%) asymptomatic, and 17 (20%) had status unknown. Outcome information at ≥6 months follow-up was available for 36 of the 47 (76%) surgically correctable and only 4 of these patients (12%) had undergone surgical or radiological intervention (carotid endarterectomy in 3 patients and carotid stenting in 1 patient). Conclusion— The frequency of carotid artery disease of at least moderate severity is very low in patients with recent stroke or TIA and there is low utilization of high-cost, carotid intervention procedures in Pakistan. These data raise questions regarding the applicability and cost-effectiveness of routine carotid ultrasound screening in our country and similar population in Asia. The local socio-economic and clinical data do not support routine carotid Doppler ultrasound in every patient with stroke and TIA in Pakistan. Studies are warranted to determine predictors of significant carotid artery stenosis in stroke/TIA patients of our country to develop reliable stroke guidelines appropriate for local population.

Lipoprotein abnormalities in South Asians and its association with cardiovascular disease: Current state and future directions

South Asians have a high prevalence of coronary heart disease (CHD) and suffer from early-onset CHD compared to other ethnic groups. Conventional risk factors may not fully explain this increased CHD risk in this population. Indeed, South Asians have a unique lipid profile which may predispose them to premature CHD. Dyslipidemia in this patient population seems to be an important contributor to the high incidence of coronary atherosclerosis. The dyslipidemia in South Asians is characterized by elevated levels of triglycerides, low levels of high-density lipoprotein (HDL) cholesterol, elevated lipoprotein(a) levels, and a higher atherogenic particle burden despite comparable low-density lipoprotein cholesterol levels compared with other ethnic subgroups. HDL particles also appear to be smaller, dysfunctional, and proatherogenic in South Asians. Despite the rapid expansion of the current literature with better understanding of the specific lipid abnormalities in this patient population, studies with adequate sample sizes are needed to assess the significance and contribution of a given lipid parameter on overall cardiovascular risk in this population. Specific management goals and treatment thresholds do not exist for South Asians because of paucity of data. Current treatment recommendations are mostly extrapolated from Western guidelines. Lastly, large, prospective studies with outcomes data are needed to assess cardiovascular benefit associated with various lipid-lowering therapies (including combination therapy) in this patient population.

Recommendations from the international stroke genetics consortium, part 1: standardized phenotypic data collection.

Risk and clinical outcome of stroke, as for nearly all complex conditions, is polygenic.1 Discovering influential genetic variants offers the promise of new and personalized treatments that will substantially reduce the devastating effects of stroke on global health. Adequate power to detect multiple genetic risk alleles requires large sample sizes. Although stroke is the second leading cause of death worldwide and a major contributor to adult disability,2 no individual center can collect sufficient samples on its own. Recognizing this challenge, in 2007, stroke researchers from around the world formed the International Stroke Genetics Consortium (ISGC, http://www.strokegenetics.org). The ISGC mission is to identify genetic factors influencing stroke risk, prognosis, and treatment response by studying patients enrolled at centers around the globe. Although there has been notable early success,3–5 much work remains not only to achieve the ultimate goal of personalized medicine in stroke, finding genetic risk alleles, but also, more importantly, to develop comprehensive stroke risk assessments with actionable clinical results.6 Judging from developments in other complex diseases, such as diabetes mellitus and coronary artery disease, sample sizes of the order of 100 000 to 200 000 will be needed to identify the full range of genetic variation involved in stroke. Achieving such sample sizes requires even larger collaboration. We propose a standard methodology for data collection in stroke genetics studies to establish a best practice approach, sharing lessons learned through the ISGC. We outline the appropriate selection of case and control subjects and delineate the phenotypic data to collect, including minimum and preferred data points. Minimum requirements are prerequisites for inclusion in basic stroke genetic studies. Preferred data elements enable centers to participate in a broader variety of collaborations, such as those exploring gene–environment interactions, imaging endophenotypes, such as white matter hyperintensities, and functional …

Mobile Health (mHealth) Technology for the Management of Hypertension and Hyperlipidemia: Slow Start but Loads of Potential

Purpose of ReviewHypertension and hyperlipidemia represent two major risk factors for atherosclerotic cardiovascular disease. Mobile health or mHealth is defined as the use of mobile phone and wireless technologies to support the achievement of health objectives. Management of hypertension, and to some extent hyperlipidemia, has often employed mHealth interventions given lower cost and greater patient engagement compared to traditional methods. These interventions include the use of text messaging, wireless devices, and mobile phone applications. This review considers recent studies evaluating the effectiveness of mHealth interventions in the management of hypertension and hyperlipidemia.Recent FindingsNumerous studies have evaluated the role of mHealth interventions in the management of hypertension, while very few have evaluated their role in hyperlipidemia. Text messaging has been used most frequently. However, the trend is shifting towards the use of mobile phone applications and wireless devices. Interventions in developing countries have been modified for greater applicability to local settings. mHealth interventions were found to be frequently effective. However, studies comparing the relative efficacy of various mHealth strategies are scarce. Long-term cardiovascular outcomes data and analyses relating to cost effectiveness are also lacking.SummarymHealth interventions may be effective in improving hypertension management. More studies are needed to evaluate the role of mHealth strategies in hyperlipidemia management, particularly in identifying high-risk individuals and improving medication adherence. Studies assessing the long-term impact of these interventions, comparing different interventions and analyzing their relative cost effectiveness, are also needed. Following recently published guidelines on reporting results of mHealth interventions will provide a more meaningful context for interpreting these promising early studies.

Risk factors of stroke in Pakistan: a dedicated stroke clinic experience.

BACKGROUND Secondary prevention of cerebrovascular disease through dedicated stroke clinics has been shown to decrease recurrent vascular events in patients. However, there is limited literature describing such stroke clinic experiences from low and middle income countries. This study describes patient characteristics and observations made at the first systematized stroke clinic in Pakistan. METHODS A retrospective audit of medical records of all patients presenting between September 2006 and August 2008 with a cerebrovascular event was conducted. Information about clinical presentation, modifiable risk factors and laboratory and radiological investigations was collected. Burden of disability was assessed using Modified Rankin score. Data was entered and analyzed using SPSS 14.0. RESULTS 159 patients with a mean age of 57.0 +/- 13.9 years were included in this study and 34.6% of all patients were women. 108 patients were diagnosed with ischemic stroke (67.9%) while 34 patients presented with hemorrhagic stroke (21.4%) and 17 patients presented with transient ischemic attacks (10.7%). Hypertension was the most common modifiable risk factor seen in 78.0%, followed by diabetes in 40.3% and dyslipidemia in 31.5%. At presentation to clinic, only 26.0% patients with dyslipidemia and 64.5% patients with hypertension were on appropriate medications. CONCLUSION A high prevalence of modifiable risk factors such as hypertension in stroke patients was observed and it presents an opportunity for conventional interventions in Pakistan. Systematized clinics for stroke and an algorithmic approach in primary care towards stroke may improve the implementation of evidence based secondary prevention strategies in developing countries.