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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.

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.

Gaps in Hypertension Guidelines in Low- and Middle-Income Versus High-Income Countries: A Systematic Review

Hypertension, a leading cause of other cardiovascular diseases, is also a leading cause of disability and death worldwide.1 Over 1 billion people are diagnosed with hypertension, such that 1 in 3 individuals has elevated blood pressure in numerous countries.2 About 90% of the burden of cardiovascular disease is borne by the low-and middle-income countries (LMIC) that have only ≈10% of the research capacity and healthcare resources to confront the scourge.3 Hypertension had been regarded as a disease of the affluent people of the world.4,5 However, it has emerged in the LMIC where it affected ≈1 in 5 adults in 2013.5 This rate has been projected to increase such that 3 in 4 adults will be living with hypertension by 2025 in LMIC.6,7 Awareness and levels of hypertension control in LMIC are still low when compared with that in HIC.8 For instance, hypertension control in United States is 52% compared with 5% to 10% in Africa.9 The major reason for this disparity could be the lack of awareness of access and adherence to implementable hypertension guidelines in LMIC.10 Furthermore, hypertension management is complicated by choice, availability, and affordability of appropriate medications. The cultural aspects of life-long use of medications for hypertension, variable needs of individual patients, and inconsistent designs and outcomes from clinical trials have also compounded the management.11 The different genetic architectures of individuals with hypertension12,13 may determine the choice and response to treatment. Some of these antihypertensive agents are costly and not evenly accessible and distributed in LMIC. Therefore, guidelines that work in HIC settings may not be acceptable, effective, implementable, and applicable to LMIC because of the lack of supporting resources. In addition to broad international guidelines tailored to the needs …

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.

Prevalence and predictors of anxiety in an African sample of recent stroke survivors.

Studies considering emotional disturbances in the setting of stroke have primarily focused on depression and been conducted in high‐income countries. Anxiety in stroke survivors, which may be associated with its own unique sets of risk factors and clinical parameters, has been rarely investigated in sub‐Saharan Africa (SSA). We assess the characteristics of anxiety and anxiety‐depression comorbidity in a SSA sample of recent stroke survivors.

The Use of Qualitative Methods in Developing Implementation Strategies in Prevention Research for Stroke Survivors in Nigeria

Implementing complex clinical interventions is a key challenge in many global regions. Local communities play a necessary role in enhancing feasibility and strengthening adaptive issues in the design and implementation of stroke interventions in developing countries. Drawing on the knowledge of physicians, patients, and caregivers, the authors employed qualitative methods as a phase 1 strategy to explore the challenges of stroke management and improve the adaptability and efficient delivery of a multimodal preventive intervention for secondary stroke disease in Nigeria. A total of 22 individual interviews were conducted with healthcare professionals, as well as 12 focus groups with patients and caregivers. Findings revealed four operational domains to improve strategies for phase 2 implementation and intervention: (1) barriers influencing optimal adherence in stroke survivors, (2) patient health beliefs and perceptions of patient health beliefs by others, (3) adoption of the “patient report card,” and (4) “medical action plan” and family management strategies.

Short-term pilot feasibility study of a nurse-led intervention to improve blood pressure control after stroke in Nigeria

BACKGROUND Given the paucity of neurologists in Sub-Saharan Africa (SSA), task-shifting post-stroke care to nurses could be a viable avenue for enhancing post-stroke outcomes. This pilot study assessed the feasibility and short-term impact of a nurse-led intervention to manage blood pressure (BP) control in recent stroke survivors in Nigeria. METHODS A randomized pilot trial allocated patients within one month of an index stroke from two participating hospitals in Nigeria to either nurse-led group clinic or standard care for 14days. Key study endpoints were successful execution of the protocol, subject retention, and short-term BP effects. RESULTS There were no significant differences between the intervention (n=17) and control (n=18) groups at baseline. At the post-intervention clinic, patient retention rate was 100%. In the intervention group, both the systolic and diastolic BPs measured at home were lower than the clinic BPs post-intervention (127±12.88/78.13±19.26mmHg versus 137.50±23.05/84.06±9.67mmHg; p=0.05). However, there was no significant change in clinic blood pressure (BP) recordings in both the intervention and control groups. CONCLUSION It is possible to initiate a nurse-led group clinic intervention to address BP management among stroke survivors in SSA with good early retention of participants. A larger and longer-term trial is being planned.

Exploring Overlaps Between the Genomic and Environmental Determinants of LVH and Stroke

Background—Whether left ventricular hypertrophy (LVH) is determined by similar genomic and environmental risk factors with stroke, or is simply an intermediate stroke marker, is unknown. We present a research plan and preliminary findings to explore the overlap in the genomic and environmental determinants of LVH and stroke among Africans participating in the Stroke Investigative Research and Education Network (SIREN) study. Methods—SIREN is a transnational, multi-centre study involving acute stroke patients and age, ethnicity and sex-matched controls recruited from 9 sites in Ghana and Nigeria. Genomic and environmental risk factors and other relevant phenotypes for stroke and LVH are being collected and compared using standard techniques. Results—This preliminary analysis included only 725 stroke patients (mean age 59.1±13.2 years; 54.3% males). Fiftyfive percent of the stroke subjects had LVH with greater proportion among women (51.6% vs 48.4%, p<0.001). Those with LVH were younger (57.9±12.8 vs 60.6±13.4; p=0.006) and had higher mean systolic and diastolic BP (167.1/99.5 mmHg vs 151.7/90.6 mmHg, p <0.001). Uncontrolled blood pressure (BP) at presentation was prevalent in subjects with LVH (76.2% vs 57.7%; p <0.001). Significant independent predictors of LVH were age, < 45 years (AOR =1.91, 95% CI: 1.14 to 3.19), female gender (AOR = 2.01; 95% CI:1.44 to 2.81), and diastolic BP > 90mmHg (AOR = 2.10; 95% CI:1.39 to 3.19, p <0.001). Conclusion—The prevalence of LVH was high among stroke patients especially the younger ones suggesting a genetic component to LVH. Hypertension was a major modifiable risk factor for stroke as well as LVH. It is envisaged that the SIREN project will elucidate polygenic overlap (if present) between left ventricular hypertrophy and stroke among Africans, thereby defining the role of LVH as a putative intermediate cardiovascular phenotype and therapeutic target to inform interventions to reduce stroke risk in populations of African ancestry. Corresponding Author: Mayowa O. Owolabi, MBBS, MSc, DM, FMCP, Department of Medicine, University College Hospital, Ibadan, Nigeria, West Africa., Phone: +234 802 077 5595, mayowaowolabi@yahoo.com. Publishers Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript Glob Heart. Author manuscript; available in PMC 2018 June 01. Published in final edited form as: Glob Heart. 2017 June ; 12(2): 107–113.e5. doi:10.1016/j.gheart.2017.01.001. A uhor M anscript

Experience of Using an Interdisciplinary Task Force to Develop a Culturally Sensitive Multipronged Tool to Improve Stroke Outcomes in Nigeria

The burden of stroke is on the rise in Nigeria. A multi-faceted strategy is essential for reducing this growing burden and includes promoting medication adherence, optimizing traditional biomarker risk targets (blood pressure, cholesterol) and encouraging beneficial lifestyle practices. Successful implementation of this strategy is challenged by inadequate patient health literacy, limited patient/medical system resources, and lack of a coordinated interdisciplinary treatment approach. Moreover, the few interventions developed to improve medical care in Nigeria have generally been aimed at physicians (primarily) and nurses (secondarily) with minimal input from other key health care providers, and limited contributions from patients, caregivers, and the community itself. The Tailored Hospital-based Risk Reduction to Impede Vascular Events after Stroke (THRIVES) study is assessing the efficacy of a culturally sensitive multidimensional intervention for controlling blood pressure in recent stroke survivors. A key component of the intervention development process was the constitution of a project task force comprising various healthcare providers and administrators. This paper describes the unique experience in Sub-Saharan Africa of utilizing of an interdisciplinary Task force to facilitate the development of the multipronged behavioral intervention aimed at enhancing stroke outcomes in a low-middle income country.

Cost and cost-effectiveness analysis of a bundled intervention to enhance outcomes after stroke in Nigeria: Rationale and design.

The economic and social costs of stroke to the society can be enormous. These costs can cause serious economic damage to both the individual and the nation. It is thus important to conduct a cost effectiveness analysis to indicate whether an intervention provides high value where its health benefits justify its costs. This study will provide evidence based on the costs of stroke with a view of improving intervention and treatments of stoke survivors in Nigeria. This study utilizes two types of economic evaluation methods – cost-effectiveness analysis and cost–benefit analysis – to determine the economic impact of Tailored Hospital-based Risk Reduction to Impede Vascular Events after Stroke (THRIVES) intervention. The study is conducted in four Nigerian hospitals where 400 patients are recruited to participate in the study. The cost-effectiveness of THRIVES post-discharge intervention is compared with the control Intervention scenario, which is the usual and customary care delivered at each health facility in terms of cost per quality adjusted life years (QALYs). It is expected that successful implementation of the project would serve as a model of cost-effective quality stroke care for implementation. Award Number: U01 NS079179. Trial registration: RL: http://www.clinicaltrials.gov. Unique identifier: NCT01900756