Sheila Adamu

Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol

Background: As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research. Methods: SIREN is a transnational, multicentre, hospital and community-based study involving 3,000 cases and 3,000 controls recruited from 8 sites in Ghana and Nigeria. Cases will be hospital-based patients with first stroke within 10 days of onset in whom neurovascular imaging will be performed. Etiological and topographical stroke subtypes will be documented for all cases. Controls will be hospital- and community-based participants, matched to cases on the basis of gender, ethnicity, and age (±5 years). Information will be collected on known and proposed emerging risk factors for stroke. Study Significance: SIREN is the largest study of stroke in Africa to date. It is anticipated that it will shed light on the phenotypic characteristics and risk factors of stroke and ultimately provide evidence base for strategic interventions to curtail the burgeoning burden of stroke on the sub-continent.

Trends in stroke admission and mortality rates from 1983 to 2013 in central Ghana

BACKGROUND Accumulating data based on model-derived estimates suggest rising rates of stroke in sub-Saharan Africa over the next several decades. Stroke is a leading cause of death, disability, and dementia worldwide. Directly enumerated hospital-based data on the longitudinal trajectory of stroke admissions and deaths in sub-Saharan Africa could help hospital administrators, public health officials, and government policy-makers with planning and utilization of scarce resources. OBJECTIVE To evaluate 30-year trends in stroke admission and mortality rates in central Ghana. METHODS We undertook a retrospective analysis of data on stroke admissions and mortality at a tertiary referral hospital in central Ghana between 1983 and 2013. Rates of stroke admissions and mortality were expressed as stroke admissions or deaths divided by total number of hospital admissions or deaths respectively. Yearly crude case fatality from stroke was calculated and predictors of stroke mortality were determined using Cox proportional hazards regression analysis. RESULTS Over the period, there were 12,233 stroke admissions with equal gender distribution. The rate of stroke admissions increased progressively from 5.32/1000 admissions in 1983 to 13.85/1000 admissions in 2010 corresponding to a 260% rise over the period. Stroke mortality rates also increased from 3.40/1000 deaths to 6.66/1000 deaths over the 30-year period. The average 28-day mortality over the period was 41.1%. Predictors of in-patient mortality were increasing age-aHR of 1.31 (1.16-1.47) for age>80years compared with <40years and admissions in 2000s compared with 1980s; aHR of 1.32 (1.26-1.39). Of the 1132 stroke patients with neuroimaging data: 569 (50.3%) had intracerebral hemorrhage, 382 (33.7%) had ischemic stroke and 181 (16.0) had sub-arachnoid hemorrhage. Patients with ischemic stroke were significantly older than those with ICH and SAH respectively. CONCLUSION Rates of stroke admission and mortality have increased steadily over the past three decades in central Ghana. More intensive risk modification and optimization of acute stroke care are urgently needed to stem these worrisome trends.

Multilingual Validation of the Questionnaire for Verifying Stroke-Free Status in West Africa

Background and Purpose— The Questionnaire for Verifying Stroke-Free Status (QVSFS), a method for verifying stroke-free status in participants of clinical, epidemiological, and genetic studies, has not been validated in low-income settings where populations have limited knowledge of stroke symptoms. We aimed to validate QVSFS in 3 languages, Yoruba, Hausa and Akan, for ascertainment of stroke-free status of control subjects enrolled in an on-going stroke epidemiological study in West Africa. Methods— Data were collected using a cross-sectional study design where 384 participants were consecutively recruited from neurology and general medicine clinics of 5 tertiary referral hospitals in Nigeria and Ghana. Ascertainment of stroke status was by neurologists using structured neurological examination, review of case records, and neuroimaging (gold standard). Relative performance of QVSFS without and with pictures of stroke symptoms (pictograms) was assessed using sensitivity, specificity, positive predictive value, and negative predictive value. Results— The overall median age of the study participants was 54 years and 48.4% were males. Of 165 stroke cases identified by gold standard, 98% were determined to have had stroke, whereas of 219 without stroke 87% were determined to be stroke-free by QVSFS. Negative predictive value of the QVSFS across the 3 languages was 0.97 (range, 0.93–1.00), sensitivity, specificity, and positive predictive value were 0.98, 0.82, and 0.80, respectively. Agreement between the questionnaire with and without the pictogram was excellent/strong with Cohen k=0.92. Conclusions— QVSFS is a valid tool for verifying stroke-free status across culturally diverse populations in West Africa.

PINGS (Phone-Based Intervention Under Nurse Guidance After Stroke): Interim Results of a Pilot Randomized Controlled Trial

Background and Purpose— Stroke exacts an immense toll in sub-Saharan Africa where there are few resources, and stroke prevention research is limited. The aim of this study is to test the feasibility and preliminary efficacy of an m-Health technology–enabled, nurse-guided intervention in improving blood pressure (BP) control among Ghanaian stroke patients within 1 month of symptom onset. Methods— We conducted a 2-arm cluster pilot randomized controlled trial involving 60 recent stroke survivors encountered within a single tertiary medical system in Ghana. Subjects in the intervention arm (n=30) received a Blue-toothed UA-767Plus BT BP device and smartphone for monitoring and reporting BP measurements and medication intake for 3 months compared with standard of care (n=30). Primary outcome measure was systolic BP <140 mm Hg at month 3; secondary outcomes included medication adherence and autonomous self-regulation. Analysis accounting for clustering was made using generalized linear mixed model by intention to treat. Results— Mean±SD age was 55±13 years, 65% male. Systolic BP <140 mm Hg at month 3 was found in 20/30 subjects (66.7%) in the intervention arm versus 14/30 subjects (46.7%) in the control arm (P=0.12). Medication possession ratio scores at month 3 were better in the intervention (0.88±0.40) versus control (0.64±0.45) arm (P=0.03). One subject in control arm died from a recurrent hemorrhagic stroke. Conclusions— It is feasible to conduct an m-Health–based, nurse-guided BP control intervention among recent stroke patients in sub-Saharan Africa. We observed a potential signal of efficacy with the intervention, which will need to be tested in a future large definitive study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT02568137.

Burden and Predictors of Poststroke Cognitive Impairment in a Sample of Ghanaian Stroke Survivors

BACKGROUND AND OBJECTIVE There are limited data on vascular cognitive impairment (VCI) from low- and middle-income countries where the stroke burden is burgeoning. The aim of this study was to characterize the burden, determinants, and effects of VCI on health-related quality of life in sub-Saharan Africa (SSA). METHODS From January 2015 to February 2016, we collected information on 147 consecutive stroke survivors (>45 years) seen at a tertiary hospital in Ghana and 49 demographically matched stroke-free controls. Data collected included demographics, clinical factors, health-related quality of life, and presence of depression. Cognitive status was evaluated using a standard Vascular Neuropsychological Battery that assessed memory, executive function and mental speed, language, and visuospatial-visuoconstructive functioning. Expert VCI guideline and Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria were used to classify stroke patients into no VCI, VCI but no dementia, and vascular dementia (VD). RESULTS The mean age ± standard deviation of the stroke survivors was 59.9 ± 13.7 years, of which 47.6% were women. Among the cohort, 77 out of 147 (52.3%) had no VCI, 50 of the 147 (34.0%) had VCI without dementia, and 20 of the 147 (13.6%) had VD. Three factors remained significantly associated with VCI: increasing age for each successive 10-year rise (odds ratio [OR] 1.44, 95% confidence interval [CI]: 1.03-2.02), lack of formal education (OR 5.26, 95% CI: 1.01-27.52), and worse functional disability on the modified Rankin scale (OR 2.46, 95% CI: 1.61-3.75). Patients with VD had the poorest health-related quality of life. CONCLUSIONS Half of the Ghanaian stroke survivors encountered in this cross-sectional study had evidence of cognitive dysfunction. Future studies in SSA will need to identify strategies to address this immense burden.

Dominant modifiable risk factors for stroke in Ghana and Nigeria (SIREN): a case-control study

Summary Background Sub-Saharan Africa has the highest incidence, prevalence, and fatality from stroke globally. Yet, only little information about context-specific risk factors for prioritising interventions to reduce the stroke burden in sub-Saharan Africa is available. We aimed to identify and characterise the effect of the top modifiable risk factors for stroke in sub-Saharan Africa. Methods The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study done at 15 sites in Nigeria and Ghana. Cases were adults (aged ≥18 years) with stroke confirmed by CT or MRI. Controls were age-matched and gender-matched stroke-free adults (aged ≥18 years) recruited from the communities in catchment areas of cases. Comprehensive assessment for vascular, lifestyle, and psychosocial factors was done using standard instruments. We used conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% CIs. Findings Between Aug 28, 2014, and June 15, 2017, we enrolled 2118 case-control pairs (1192 [56%] men) with mean ages of 59.0 years (SD 13.8) for cases and 57.8 years (13.7) for controls. 1430 (68%) had ischaemic stoke, 682 (32%) had haemorrhagic stroke, and six (<1%) had discrete ischaemic and haemorrhagic lesions. 98.2% (95% CI 97.2–99.0) of adjusted PAR of stroke was associated with 11 potentially modifiable risk factors with ORs and PARs in descending order of PAR of 19.36 (95% CI 12.11–30.93) and 90.8% (95% CI 87.9–93.7) for hypertension, 1.85 (1.44–2.38) and 35.8% (25.3–46.2) for dyslipidaemia, 1.59 (1.19–2.13) and 31.1% (13.3–48.9) for regular meat consumption, 1.48 (1.13–1.94) and 26.5% (12.9–40.2) for elevated waist-to-hip ratio, 2.58 (1.98–3.37) and 22.1% (17.8–26.4) for diabetes, 2.43 (1.81–3.26) and 18.2% (14.1–22.3) for low green leafy vegetable consumption, 1.89 (1.40–2.54) and 11.6% (6.6–16.7) for stress, 2.14 (1.34–3.43) and 5.3% (3.3–7.3) for added salt at the table, 1.65 (1.09–2.49) and 4.3% (0.6–7.9) for cardiac disease, 2.13 (1.12–4.05) and 2.4% (0.7–4.1) for physical inactivity, and 4.42 (1.75–11.16) and 2.3% (1.5–3.1) for current cigarette smoking. Ten of these factors were associated with ischaemic stroke and six with haemorrhagic stroke occurrence. Interpretation Implementation of interventions targeting these leading risk factors at the population level should substantially curtail the burden of stroke among Africans. Funding National Institutes of Health.

Long-Term Outcomes of Stroke in a Ghanaian Outpatient Clinic

BACKGROUND Compared with high-income countries, sub-Saharan African (SSA) countries experience a comparatively higher early mortality from stroke. However, data on long-term mortality from stroke in SSA are lacking. OBJECTIVE Our aim is to assess long-term outcomes of stroke in an SSA setting. METHODS We conducted a retrospective analysis of longitudinal data involving 607 consecutive stroke survivor encountered at an outpatient clinic in Kumasi, Ghana, between January 2012 and June 2014. Data were closed for analysis in June 2016. Data on demography, presence of vascular risk factors, stroke type, and functional status were evaluated. We followed up subjects who were no longer attending clinic by phone to assess their vital status. Primary outcome was death after initiation of clinic care, and its predictors were determined using a Cox proportional hazards regression model. RESULTS Mean ± standard deviation (SD) age of cohort was 59.9 ± 13.9 years and 50.3% were female. Of the 607 stroke survivors, 377 (62.1%) were still alive, 59 (9.7%) were confirmed to have died, whereas 171 (28.2%) were lost to follow-up at the clinic. Mean ± SD observation time for the cohort was 32 ± 30 months. Upon adjustment for confounders, the independent predictors of mortality were age (adjusted hazard ratio [aHR] of 1.41 [95% confidence interval 1.15-1.73] for a 10-year increase in age) and diabetes mellitus (aHR of 2.24 [1.32-3.80]). CONCLUSIONS Diabetes mellitus, a modifiable risk factor for stroke, is associated with an increased risk of mortality among West African stroke survivors over the long term.

Administration of a pictorial questionnaire to screen for stroke among patients with hypertension or diabetes in rural Ghana

BACKGROUND Stroke prevention is an important public health goal in low-and-middle income countries (LMIC) due to its high mortality and morbidity in these settings. Epidemiological data from high-income countries have demonstrated a potent predictive association between self-reported stroke symptoms and risks of future strokes, incident cognitive impairment and all-cause mortality. OBJECTIVE To utilize a pictographic version of the 8-item Questionnaire for Verifying Stroke Free Status (QVSFS) to screen for stroke symptoms and determine its predictors among hypertensive and diabetic patients in a rural hospital within a LMIC. METHODS Between July and October 2016, 500 consecutive patients with hypertension and/or diabetes mellitus encountered in clinic at the Agogo Presbyterian Hospital, a district level health institution in Ghana were enrolled. A validated pictographic version of the QVSFS was administered by trained research assistants to all study participants and demographic and clinical information on hypertension and diabetes control were collected. The neurologist/specialist physician examined all patients neurologically using a structured questionnaire and reviewed medical charts for objective documentary evidence of stroke. Predictors of stroke symptoms were assessed using a multivariate logistic regression model. RESULTS Among the cohort, median (IQR) age was 58 (51-66) years, 399 (79.8%) were women, 388 (77.6%) had hypertension, 92 (18.4%) had diabetes and hypertension, and 20 (4.0%) had just diabetes. 30 (6.0%) patients had confirmed stroke/TIA after physician evaluation, 151 (30.6%) had at least one symptom of stroke (SS) without prior diagnosis of stroke/TIA and 319 (63.8%) reported no stroke symptoms. Independent predictors of reporting stroke symptoms were increasing age - aOR: 1.38 (1.16-1.64) for each 10years older and HBA1C-OR: 1.74 (1.16-2.61) for each 2% increase. Subjects with previous stroke/TIA diagnosis had significantly higher mean±SD systolic blood pressure (148.0±21.2mmHg vs. 136.0±17.3mmHg vs. 138.3±19.7mmHg, p=0.009) and median (IQR) HBA1C (8.8% (6.7-10.2) vs. 8.2 (6.4-10.6) vs. 7.2 (6.3-8.0), p=0.05) compared with SS and asymptomatic groups. CONCLUSION One in three patients with hypertension and/diabetes in rural Ghana report stroke-like symptoms. Routine use of the pictographic version of the QVSFS could assist in identifying patients with or at high risk for stroke who may benefit from appropriate prevention treatments.

Plasma Glial Fibrillary Acidic Protein, Copeptin, and Matrix Metalloproteinase-9 Concentrations among West African Stroke Subjects Compared with Stroke-Free Controls

BACKGROUND Measurement of plasma molecular markers among stroke patients has been proposed as an avenue for improving the accuracy of stroke diagnosis. There is paucity of data on the potential role of these markers in resource-limited settings, where the burden of stroke is greatest. OBJECTIVE To assess the potential diagnostic and prognostic performance of 3 proposed biomarkers for stroke in a resource-constrained setting. METHODS Consecutive stroke subjects presenting at a tertiary medical center in Kumasi, Ghana, with radiologically confirmed diagnosis and etiologic subtype information available were recruited along with age- and gender-matched controls in a 2:1 ratio. Plasma concentrations of glial fibrillary acidic protein (GFAP), copeptin, and matrix metalloproteinase-9 (MMP-9) among stroke patients and stroke-free controls were measured in duplicates using enzyme linked immunoassays. Diagnostic and prognostic correlates were assessed using area-under-the-curve (AUC) measures of receiver operator curves and logistic regression analysis, respectively. RESULTS There were 156 stroke subjects with a mean age of 61.3 years of which 47.4% were females and 74 age- and gender-matched stroke-free controls. Median (interquartile range) time from symptom onset to hospital presentation for care was 7 days (5-11). Diagnostic accuracy of a single measurement of the 3 biomarkers for stroke using AUC (95% confidence interval) plots were as follows: .84 (.77-0.91), P < .0001, for GFAP; .85 (.79-0.92), P < .0001, for copeptin; and .65 (.56-0.73), P = .0003, for MMP-9. None of the biomarkers was associated with stroke severity or mortality. CONCLUSION Plasma concentrations of GFAP and copeptin demonstrated stronger associations with stroke occurrence in this West African cohort compared with controls.

Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART): study protocol for a randomized controlled trial

BackgroundThere is an unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA). Secondary prevention guidelines recommend that antihypertensive, statin and antiplatelet therapy be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular-risk reduction. However, these goals are seldom realized in routine clinical care settings in SSA due to logistical challenges.We seek to assess whether a polypill containing fixed doses of three antihypertensive agents, a statin and antiplatelet therapy taken once daily per os for 12 months among recent stroke survivors would result in carotid intimal thickness regression compared with usual care (UC).MethodsThe Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART) trial is a phase 2, open-label, evaluator-blinded trial involving 120 Ghanaian recent-ischemic-stroke survivors. Using a computer-generated sequence, patients will be randomly allocated 1:1 into either the intervention arm or UC. Patients in the intervention arm will receive Polycap DS® (containing aspirin, 100 mg; atenolol, 50 mg; ramipril, 5 mg; thiazide, 12.5 mg; simvastatin, 20 mg) taken as two capsules once daily. Patients in the UC will receive separate, individual secondary preventive medications prescribed at the physician’s discretion. Both groups will be followed for 12 months to assess changes in carotid intimal thickness regression – a surrogate marker of atherosclerosis – as primary outcome measure. Secondary outcome measures include adherence to therapy, safety and tolerability, health-related quality of life, patient satisfaction, functional status, depression and cognitive dysfunction.DiscussionAn efficacy-suggesting SMAART trial could inform the future design of a multi-center, double-blinded, placebo-controlled, parallel-group, randomized controlled trial comparing the clinical efficacy of the polypill strategy for vascular risk moderation among stroke survivors in SSA.Trial registrationClinicalTrials.gov, ID: NCT03329599. Registered on 11 February 2017.