Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans.

BACKGROUND: African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans. METHODS: Cases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation. RESULTS: We observed genome-wide significant (P-value < 5.0E-8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E-6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E-6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E-6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping. CONCLUSIONS: Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke's risk prediction and development of new targeted interventions to prevent or treat stroke.

Effect of an Educational Intervention for Primary Stroke Risk Reduction in Ghana and Nigeria: Pilot Randomized Controlled Trial.

BACKGROUND: Using tailored mobile health interventions to improve global vascular risk awareness and control is yet to be investigated for primary stroke prevention in Africa. METHODS: This 2-arm pilot randomized controlled trial involved 100 stroke-free adults with at least 2 vascular risk factors for stroke. Eligible participants were assigned randomly to a control arm offering 1-time counseling (n=50) or a 2-month educational intervention arm (n=50) comprising a stroke video and riskometer app aimed at improving stroke risk factor awareness and health-seeking behavioral modification to control total vascular risk. Reduction in total stroke risk score was the primary outcome while feasibility and process measures were secondary outcomes. RESULTS: All enrolled participants completed the 2-month follow-up (retention rate=100%). The mean (SD) age of participants was 59.5 (±12.5) years, 38% were males. The mean change in stroke risk score at 2 months was -11.9% (±14.2) in the intervention arm versus -1.2% (±9.1) in the control arm, P=0.0001. Stroke risk awareness improved by 16.1% (±24.7) in the intervention arm versus 8.9% (±24.7) in the control arm, P=0.08. The intervention arm had 11.1 mm Hg reduction in systolic blood pressure compared with 4.8 mm Hg reduction in the control arm. CONCLUSIONS: The intervention demonstrated a positive signal of effect over a 2-month period. A definitive clinical trial with a longer duration of follow-up is warranted on the premise of these promising findings from this pilot randomized clinical trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05619406.

Pilot trial of a tele-rehab intervention to improve outcomes after stroke in Ghana: A feasibility and user satisfaction study.

BACKGROUND: Tele-rehabilitation after stroke holds promise for under-resourced settings, especially sub-Saharan Africa (SSA), with its immense stroke burden and severely limited physical therapy services. OBJECTIVE: To preliminarily assess the feasibility and outcomes of mobile technology-assisted physical therapy exercises for stroke survivors in Ghana. METHODS: We conducted a prospective, single arm, pre-post study involving 20 stroke survivors recruited from a tertiary medical center, who received a Smartphone with the 9zest Stroke App® to deliver individualized, goal-targeted 5-days-a-week exercise program that was remotely supervised by a tele-therapist for 12 weeks. Outcome measures included changes in stroke levity scale scores (SLS), Modified Rankin score (MRS), Montreal Cognitive Assessment (MOCA), and feasibility indicators. RESULTS: Among study participants, mean ±â€¯SD age was 54.6 ±â€¯10.2 years, 11 (55%) were men, average time from stroke onset was 6 months. No participants dropped out. Compared with baseline status, mean ±â€¯SD scores on SLS improved from 7.5 ±â€¯3.1 to 11.8 ±â€¯2.2 at month 1 (p < 0.0001) and 12.2 ±â€¯2.4 at month 3 (p < 0.0001), MOCA scores improved from 18.2 ±â€¯4.3 to 20.4 ±â€¯4.7 at month 1 (p = 0.14), and 22.2 ±â€¯7.6 at month 3 (p = 0.047). Mean ±â€¯SD weekly sessions performed by participants per month was 5.7 ±â€¯5.8 and duration of sessions was 25.5 ±â€¯16.2 min. Erratic internet connectivity negatively affected full compliance with the intervention, although satisfaction ratings by study participants were excellent. CONCLUSION: It is feasible to administer an m-health delivered physical therapy intervention in SSA, with high user satisfaction. Randomized trials to assess the efficacy and cost-effectiveness of this intervention are warranted.

Post-stroke depression in Ghana: Characteristics and correlates.

BACKGROUND: Poststroke depression (PSD) is prevalent and is an important determinant of functional recovery, quality of life and mortality after stroke. Scanty data on the nature of PSD among stroke survivors in sub-Saharan Africa prompted this study. OBJECTIVE: To assess the prevalence and predictors of depression in a convenience sample of Ghanaian stroke survivors. METHODS: We evaluated consecutive stroke survivors encountered at a comprehensive neurology clinic in a tertiary medical center in Ghana. The Center for Epidemiologic Studies Depression Scale (CES-D) and Geriatric Depression Scale (GDS) were both used to screen for depressive symptoms and subjects were considered as depressed if they scored ≥16 on the CES-D scale and >5 on the GDS. Demographic and clinical data on stroke type and severity as well as health-related quality of life indicators were collected. Predictors of stroke-related depression were assessed using a logistic regression model. RESULTS: Of 200 stroke survivors, mean±SD age was 62.0±14.4years, and 105 (52.5%) patients were men. Among the cohort 78.5% were classified as being depressed by CES-D, 42.5% by GDS, and 36.5% on both CES-D and GDS. In multivariable analyses, for each unit increase on the Modified Rankin scale (i.e. worsening disability), there were higher odds of depression (adjusted OR 1.85; 1.28-2.69, p=0.001), and being divorced (vs. being married) was linked to depression (adjusted 2.82; 1.18-6.71, p=0.02). Stroke survivors with depression demonstrated profound diminutions in the physical, psycho-social, cognitive and eco-social domains of quality of life compared with those without depression (p<0.05). CONCLUSION: Almost 4 out of 10 stroke survivors in this Ghanaian cohort displayed clinically significant depression. Prospective interventional studies are urgently needed to provide solid evidence-based and culturally tailored interventions to address post-stroke depression particularly in LMICs.