A contemporary evaluation of the frequency & factors associated with overt stroke across the lifespan: A Ghanaian sickle cell disease registry analysis.

BACKGROUND: Stroke is a devastating complication of Sickle Cell Disease (SCD) with significant mortality and substantial morbidity. The burden of prevalent stroke in SCD is highest in sub-Saharan Africa and estimated at 4.2 % to 6.4 % in the era where evidence-based prevention strategies such as use of hydroxyurea therapy and transcranial doppler ultrasound were not routine care. PURPOSE: To assess the contemporary frequency and factors associated with prevalent stroke across the lifespan in an SCD registry at the tertiary medical center in Ghana. METHODS: This is a cross-sectional study conducted at the Komfo Anokye Teaching Hospital, a tertiary medical center in the middle belt of Ghana. The center has comprehensive Sickle Cell Clinics for children, adolescents, and adults with a patient registry established as part of the Sickle Pan-African Research Consortium (SPARCo)-Ghana study from 2017 to date. Data captured in the registry and analyzed for the present study include demographics, stroke status using the WHO criteria supplemented by the Questionnaire for Verifying Stroke Free Status (QVSFS), use of hydroxyurea, and complete blood count. Logistic regression modeling was utilized to assess factors associated with stroke. RESULTS: Among a registry cohort of 4115 individuals with confirmed SCD, 35 (0.85 %, 95 % CI: 0.59-1.18 %) had overt or clinically confirmed stroke. The frequency of stroke differed significantly across the lifespan being 0.38 % (95 % CI: 0.12-0.64 %) among children <10 years, 1.23 % (95 % CI: 0.73-1.94 %) among adolescents aged 10 to 17 years, and 1.44 % (95 % CI: 0.66-2.71 %) among adults 18 years or more, p = 0.007. In adjusted analysis, each 10-year increase in age was associated with odds ratio, OR (95 % CI) of 1.90 (1.42-2.54) and hydroxyurea use, OR of 6.09 (2.65-13.99). The association between hydroxyurea and stroke observed in this cross-sectional study is not causal. CONCLUSION: Approximately 1 in 120 SCD patients in this large Ghanaian cohort had clinically overt stroke. The gradual uptake of hydroxyurea therapy into routine care for SCD in this resource-limited setting, may partly explain the lower frequency of stroke.

Absence of measurable quantities of Candida auris and Cryptococcus spp. in the gut microbiota of Ghanaian individuals with and without HIV infection as confirmed by applying multiple real-time PCR assays.

Introduction. Fungal infections are relevant health risks for individuals with acquired immunodeficiency in the resource-limited tropics, but available surveillance data are scarce. For Candida auris and Cryptococcus spp., the evolution from environmental reservoirs to human pathogens causing life-threatening diseases is currently discussed as a public health concern in the context of climate change and limited treatment options.Gap statement. Uncovering the gastrointestinal tract as an epidemiological niche of fungi emerging from the environment into individuals for whom fungal infections are not diagnosed.Aim. To contribute to data on the local epidemiology of C. auris and Cryptococcus spp. in Western African Ghana by analysing gastrointestinal samples of Ghanaian individuals.Methodology. Four real-time PCR assays targeting C. auris and five real-time PCR assays targeting Cryptococcus spp. were applied with stool samples of 875 non-age-stratified Ghanaian HIV patients and 30 Ghanaian control individuals without known HIV infection. Also, 664 samples from Ghanaian children under 2 years of age were investigated. The true abundance of the target micro-organism was considered as unlikely in the case of one or fewer positive signals, likely in the case of two to three positive signals and highly likely in the case of four or more positive signals per sample in the real-time PCR assays.Results. The combined application of sensitive, target-specific real-time PCR assays indicates that neither C. auris, Cryptococcus neoformans complex nor Cryptococcus gattii complex were part of the gut microbiota of Ghanaian individuals with or without HIV infection.Conclusion. Despite the significant disease burden from these pathogens in immunosuppressed Ghanaian individuals, detection from gastrointestinal samples was unlikely, which should be taken into account when discussing screening strategies for these fungi of public health concern. In contrast, the detection of these fungi from such samples should not routinely be considered as commensal colonization flora.

Replicative co-infections with human immunodeficiency virus 1 and 2 as well as hepatitis B and C virus in Ghanaian individuals.

Background: The study assessed replicative human immunodeficiency virus-(HIV-) infection and replicative co-infections as well as molecular determinants of reduced susceptibility towards anti-retroviral therapy in a Ghanaian population of known HIV patients and a control group. Methods: Real-time PCRs for HIV-1, HIV-2, hepatitis B virus (HBV) and hepatitis C virus (HCV) were run with serum samples from known Ghanaian HIV-patients (n = 975) and control individuals (n = 105). For 108 individuals, HIV-sequence analysis was performed. Results: Prevalence of replicative HIV-1 infection was 59.8% (583/975) in the known HIV-positive population and 2.9% (3/105) in the controls. Prevalences of replicative HBV-infection were comparable with 3.4% (33/975) in the HIV-positive individuals and 3.8% (4/105) in the controls. HIV-2 and HCV sequences were not recorded. Almost perfect concordance between two compared HIV-1-PCR assays was indicated by Fleiss' Kappa >0.8. Sanger sequencing indicated CRF_02AG, G and A3 as the quantitatively dominating HIV-1 subtypes, a minority of 3.4% CXCR4 tropism and high detection rates of mutations mediating reduced susceptibility towards nucleoside reverse transcriptase inhibitors (71.9%, 64/89), non-nucleoside reverse transcriptase inhibitors (95.5%, 85/89), protease inhibitors (95.9%, 93/97) and integrase inhibitors (22.4%, 22/98). Conclusions: The assessment did not suggest HIV-triggered increased replication of HBV and HCV in the investigated Ghanaian population.

The association of blood pressure, body mass index and carotid intima-media thickness as childhood predictors of cardiovascular disease risk: A systematic review and meta-analysis.

Background and Aims: Blood pressure, body mass index (BMI), and carotid intima-media thickness (CIMT) are well-known independent predictors of cardiovascular disease especially in adulthood. However, there is insufficient evidence regarding the statistical significance of the relationship between childhood CIMT, blood pressure and BMI. This systematic review and meta-analysis was therefore conducted to ascertain the relationship. Methods: This systematic review and meta-analysis was reported in accordance with the PRISMA statement. Three electronic databases were searched, namely EMBASE, MEDLINE and the Cochrane Library. Data were extracted independently by two review authors. Quantitative data were analyzed using Review Manager. Results: The meta-analysis was conducted using a random effects model and standard mean difference. The results of the meta-analysis indicated a statistically significant difference in CIMT of 0.86 (95% CI: 0.41-1.31) between normotensive versus hypertensive children. Again, overweight and moderately obese children had higher CIMT values as compared to normal weight children with a pooled standard mean difference of 0.72 (95% CI: 0.24-1.20) and 2.75 (95% CI: 0.73-4.77) respectively. The pooled standard mean difference of systolic and diastolic blood pressures was found to be 2.44 (95% CI: 1.69-3.19) and 1.28 (95% CI: 0.65-1.92) respectively between normal weight and overweight/obese children. Conclusion: The meta-analysis found a significant difference in CIMT between normotensive and hypertensive children, with overweight and moderately obese children having higher CIMT values. Thus, conducting CIMT screening for obese or overweight children and children with increased blood pressure can provide valuable information about their cardiovascular disease risk.

Protocol for a mixed-methods study to explore implementation outcomes of the Phone-based Interventions under Nurse Guidance after Stroke (PINGS-II) across 10 hospitals in Ghana.

BACKGROUND: Stroke survivors are at a substantially higher risk for adverse vascular events driven partly by poorly controlled vascular risk factors. Mobile health interventions supported by task shifting strategies have been feasible to test in small pilot trials in low-income settings to promote vascular risk reduction after stroke. However, real-world success and timely implementation of such interventions remain challenging, necessitating research to bridge the know-do gap and expedite improvements in stroke management. The Phone-based Interventions under Nurse Guidance after Stroke (PINGS-II) is a nurse-led mHealth intervention for blood pressure control among stroke survivors, currently being assessed for efficacy in a hybrid clinical trial across 10 hospitals in Ghana compared with usual care. This protocol aims to assess implementation outcomes such as feasibility, appropriateness, acceptability, fidelity, cost and implementation facilitators and barriers of the PINGS-II intervention. METHODS AND ANALYSIS: This study uses descriptive mixed methods. Qualitative data to be collected include in-depth interviews and FGDs with patients who had a stroke on the PINGS-II intervention, as well as key informant interviews with medical doctors and health policy actors (implementation context, barriers and facilitators). Data will be analysed by thematic analysis. Quantitative data sources include structured questionnaires for clinicians (feasibility, acceptability and appropriateness), and patients who had a stroke (fidelity and costs). Analysis will include summary statistics like means, medians, proportions and exploratory tests of association including χ2 analysis. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Committee for Human Research Publication and Ethics at the Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Voluntary written informed consent will be obtained from all participants. All the rights of the participants and ethical principles guiding scientific research shall be adhered to. Findings from the study will be presented in scientific conferences and published in a peer-reviewed scientific journal. A dissemination meeting will be held with relevant agencies of the Ghana Ministry of Health, clinicians, patient group representatives, and non-governmental organisations.

Towards improving stroke services in Africa: Results from the Africa-UK Stroke Partnership [AUKSP] surveys.

BACKGROUND: The African Stroke Organization (ASO) in partnership with the University of Central Lancashire's Stroke Research Team launched the Africa-UK Stroke Partnership (AUKSP). AUKSP undertook two (stroke expert and hospital Stroke Unit (SU)) on-line surveys mapping existing capacity and capability to deliver African stroke care. METHODS: An on-line expert survey tool was sent to 139 stroke experts in 54 African countries October 2021-March 2022 and the hospital SU survey to 120 hospital SUs (identified from the expert survey) June-October 2022. Both survey tools were prepared according to the World Stroke Organisation's Roadmap for Delivering Quality Stroke Care. Completed responses were exported from Qualtrics into Microsoft excel and were analysed descriptively. RESULTS: Forty-five expert responses and 62 hospital SU responses were analysed, representing 54(87%) public hospitals, 7(11%) private and 1(2%) charitable organization. In both surveys, three main priorities for improvement of stroke services were: a rapid and prompt stroke diagnosis; effective primary and secondary stroke prevention, and acute stroke management. Survey findings suggest that there is a low presence of national stroke surveillance systems and registries, and heterogeneity in availability of diagnostic services, SUs, endovascular treatments, and rehabilitation. CONCLUSION: Significant gaps exist in Africa's capacity and capability to deliver essential elements of effective and quality stroke care. Tackling these challenges requires urgent and sustained multi-stakeholder action including: government, administrators, policy makers and other partners. Our survey findings highlight key priority areas for multi-stakeholder engagement and crafting of a pragmatic, prioritized and context-sensitive African Stroke Action Plan.

Healthcare system barriers and facilitators to hypertension management in Ghana.

Background: Hypertension continues to pose a significant burden on the health systems in Sub-Saharan Africa (SSA). Multiple challenges at the health systems level could impact patients' blood pressure outcomes. There is a need to understand the gaps in health systems to improve their readiness to manage the rising burden of hypertension Objective: To explore health system barriers and opportunities for improved management of hypertension in Ghana, West Africa. Methods: We conducted 5 focus group discussions involving 9 health facility leaders and 24 clinicians involved in hypertension treatment at 15 primary-level health facilities in Kumasi, Ghana. We held discussions remotely over Zoom and used thematic analysis methods. Results: Four themes emerged from the focus group discussions: (1) financial and geographic inaccessibility of hypertension services; (2) facilities' struggle to maintain the supply of antihypertensive medications and providers' perceptions of suboptimal quality of insured medications; (3) shortage of healthcare providers, especially physicians; and (4) patients' negative self-management practices. Facilitators identified included presence of wellness and hypertension clinics for screening and management of hypertension at some health facilities, nurses' request for additional roles in hypertension management, and the rising positive practice of patient home blood pressure monitoring. Conclusion: Our findings highlight critical barriers to hypertension service delivery and providers' abilities to provide quality services. Health facilities should build on ongoing innovations in hypertension screening, task-shifting strategies, and patient self-management to improve hypertension control. In Ghana and other countries, policies to equip healthcare systems with the resources needed for hypertension management could lead to a high improvement in hypertension outcomes among patients.

Exploring patient-, provider-, and health facility-level determinants of blood pressure among patients with hypertension: A multicenter study in Ghana.

Optimal blood pressure (BP) control is essential in averting cardiovascular disease and associated complications, yet multiple factors influence the achievement of BP targets. We explored patient-, provider-, and health facility-level factors of systolic and diastolic BP and controlled BP status among patients with hypertension in Ghana. Using a cross-sectional design, we recruited 15 health facilities, and from each facility, we recruited four healthcare providers involved in managing hypertension and 15 patients diagnosed with hypertension. The primary outcome of interest was systolic and diastolic BP; the secondary outcome was BP control (<140/90 mmHg) in compliance with Ghana's national standard treatment guidelines. We used mixed-effects regression models to explore the patient- and facility-level predictors of the outcomes. Two hundred twenty-four patients and 67 healthcare providers were sampled across 15 health facilities. The mean (SD) age of providers and patients was 32 (7) and 61 (13) years, respectively. Most (182 [81%]) of the patient participants were female, and almost half (109 [49%]) had controlled BP. At the patient level, traveling for 30 minutes to one hour to the health facility was associated with higher diastolic BP (Coeff.:3.75, 95% CI: 0.12, 7.38) and lower odds of BP control (OR: 0.51, 95% CI: 0.28, 0.92) compared to traveling for less than 30 minutes. Receiving hypertension care at government health facilities than at private health facilities was associated with lower systolic BP (Coeff.: -13.89; 95% CI: -23.99, -3.79). A higher patient-to-physician or physician-assistant ratio was associated with elevated systolic BP (Coeff.: 21.34; 95% CI: 8.94, 33.74) and lower odds of controlled BP (OR: 0.19, 95% CI: 0.05, 0.72). Along with addressing the patient-level factors influencing BP outcomes in Ghana, there is a need for public health and policy interventions addressing the inaccessibility of hypertension services, the shortage of clinical care providers, and the underperformance of private health facilities.

Clustering of Gastrointestinal Microorganisms in Human Stool Samples from Ghana.

The study was conducted to identify cluster patterns of enteric microorganisms with potential etiological relevance for infectious gastroenteritis in stool samples of individuals from Ghana, which is a known high-endemicity setting for infectious gastroenteritis. These patterns were compared to previous observations with specimens from Colombian indigenous people in order to assess potentially stable clustering for temporally and spatially distinct populations from high-endemicity regions. By doing so, the study aimed to identify stable clusters as markers of microbial interaction with potential importance for etiological relevance assignment in cases of multiple enteric pathogen detections. Stool samples from 1569 Ghanaian individuals (875 from HIV patients, 30 from HIV-negative control adult patients, and 644 from children < 2 years of age) were assessed for enteric microorganisms by applying real-time PCR. As a result, nucleic acids of bacterial microorganisms were most frequently detected, followed by protozoa, microsporidia, and helminths. Interestingly, the cluster assessment confirmed interaction patterns known from the previous analysis with Colombian indigenous people, demonstrating a high likelihood of Blastocystis hominis for clustering with other microorganisms and a prominent, potentially mediating role of Dientamoeba fragilis for microbial interactions within the clusters. In conclusion, the assessment confirmed conserved clustering of enteric microorganisms with potential etiological relevance for human infectious gastroenteritis over geographically distinct high-endemicity settings. Furthermore, the composition of abundant microorganisms is more important than regional factors for the determination of the interplay of enteric microorganisms in the human gut. Thereby, some microbial pathogens and commensals seem more susceptible to a changing microbial composition in the human gut than others.

Effect of a Cardiovascular Polypill on Poststroke Cognition Among Ghanaians: Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: Poststroke cognitive impairment is prevalent worldwide, with no satisfactory preventative therapeutic strategies. We report on the effect of a cardiovascular polypill on cognitive performance among recent stroke survivors. METHODS AND RESULTS: The SMAART (Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment) trial was a phase II randomized trial primarily assessing the polypill versus usual care for secondary prevention after a recent ischemic stroke. Participants allocated to the experimental arm were provided 2 Polycaps taken orally once a day for 12 months. A capsule of Polycap contained aspirin 100 mg, simvastatin 20 mg, hydrochlorothiazide 12.5 mg, ramipril 5 mg, and atenolol 50 mg. Participants in the usual care arm received standard secondary prevention therapy. We compared slopes of the trajectory of raw scores in the executive, language, memory, and visuospatial cognitive domains and aggregated cognitive scores over 12 months via a linear mixed-effects model. We enrolled 148 eligible participants (n=74 in each arm) and 59 versus 64 participants in the polypill and usual care arms, respectively, at month 12. Compared with the usual care arm, the slopes of cognitive performance over 12 months in the polypill arm were steeper by 2.02 units (95% CI, 0.52-3.53), P=0.009 in executive domain, 1.88 units (95% CI, 0.42-3.34), P=0.012 in language domain, 2.60 (0.03-5.17), P=0.049 in memory domain, 0.55 (-0.80 to 1.91), P=0.42 in the visuospatial domain, and global cognitive performance 6.87 units (95% CI, 1.44-12.30), P=0.013. CONCLUSIONS: The cardiovascular polypill is associated with a signal of better cognitive performance over 12 months among stroke survivors. Further definitive trials are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03329599.

Prevalence and predictors of long-term progression of chronic kidney disease in people with HIV in Ghana from 2003-2018.

BACKGROUND: HIV is associated with an increased risk of progression to chronic kidney disease (CKD), and this risk is higher in people of West African descent than many other ethnicities. Our study assessed the rates of eGFR change and predictors of rapid eGFR progression in patients receiving antiretroviral therapy (ART), including tenofovir disoproxil fumarate (TDF), in central Ghana between 2003 and 2018. METHODS: This single-centre retrospective study enrolled people with HIV (PWH) initiating ART in Ghana between 2003-2018. Demographics, hepatitis B (HBsAg) status, ART regimens and estimated glomerular filtration rate (eGFR) measurements were recorded, and analyses including multi-level model linear regression were performed to determine predictors of greater levels of eGFR decline and risk of rapid eGFR decline. RESULTS: Six hundred and fifty-nine adult participants were included in the study with a median follow-up time of 6 years (IQR 3.6-8.9). 149 participants (22.6%) also had confirmed HBV co-infection. eGFR mean values were lowest at the point of diagnosis and highest on the second measurement taken; mean eGFR slowly decreased over subsequent measures thereafter. TDF use was associated with the highest mean rate of eGFR decline of all nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) with a statistically significant greater annual decline of -1.08 mL/min/1.73m2/year (CI: -1.92, -0.24) compared with zidovudine. Nevirapine (-0.78mL /min/173m2/year; CI: -1.39, -0.17) and protease inhibitors (-1.55mL/mil/173m2/year; CI: -2.68, -0.41) were associated with greater eGFR declines compared with efavirenz. Negative HBsAg status was associated with greater eGFR decline compared with positive HBsAg status (-1.25mL/mil/173m2/year; CI 0.29. -2.20). CONCLUSIONS: Increased rates of eGFR decline amongst PWH in Ghana were associated with TDF, nevirapine, and protease inhibitor use as well as negative HBsAg status. Additional research using mortality outcome data is needed to closely assess long-term predictors of eGFR decline in African populations.

Dyke-Davidoff-Masson syndrome-A rare cause of recurrent seizures in adulthood.

It is important to consider DDMS as a differential diagnosis in any patient with early childhood onset of epilepsy. Early diagnosis and optimal management are key to reducing the disabling effect of DDMS.

Mucuna pruriens to treat Parkinson's disease in low-income countries: Recommendations and practical guidelines from the farmer to clinical trials. Paving the way for future use in clinical practice.

Parkinson's disease (PD) is a progressive and disabling neurodegenerative disease that rapidly worsens and results in premature mortality if left untreated. Although levodopa is the gold standard treatment for PD globally, its accessibility and affordability are severely limited in low- and middle-income countries worldwide. In this scenario, Mucuna pruriens (MP), a leguminous plant growing wild in tropical regions, emerges as a potential alternative or adjunct to levodopa-based medications due to its cost-effectiveness and global natural availability. Recent studies have demonstrated that MP can significantly ameliorate motor symptoms, although tolerability may vary. The proposition that MP could play a pivotal role in providing affordable and symptomatic relief for PD in low- and middle-income countries is grounded in its promising therapeutic profile, yet caution is warranted until more comprehensive data on the long-term safety and efficacy of MP become available. This manuscript summarizes the knowledge gained about MP by the authors, focusing on how to cultivate, store, and provide it to patients in the safest and most effective way in clinical trials. We aim to increase clinical trials investigating its safety and efficacy in PD, before promoting individual use of MP on a global scale, particularly in countries where availability and affordability of levodopa-based medications is still limited.

Views of Service Users, Their Family or Carers, and Health Care Professionals on Telerehabilitation for People With Neurological Conditions in Ghana: Qualitative Study.

BACKGROUND: Up to 50% of people in low- and middle-income countries do not receive the rehabilitation they require. Telerehabilitation has the potential to improve access to neurorehabilitation services especially in low- and middle-income countries. Although there are reports of the barriers and facilitators to telerehabilitation in such settings, almost all are anecdotal. Furthermore, family or carers have a significant influence on the adoption and success of telerehabilitation, but their views have not been reported. OBJECTIVE: This study aimed to investigate the views of service users, their family or carers, and health care professionals (HCPs) on telerehabilitation for people with neurological conditions in Ghana. METHODS: Two focus groups were held at Komfo Anokye Hospital in Kumasi, Ghana: one in person for service users (n=11) and their family or carers (n=9), conducted in the Ghanaian language of Twi, and one hybrid for HCPs (n=18) conducted in English. The mean (SD) age of the service users was 59.8 (8.6) years; 5 users had a stroke and 6 had Parkinson disease. The HCP group consisted of 7 speech and language therapists, 3 physiotherapists, 3 occupational therapists, 3 medical staff, 1 nurse, and 1 industry representative. Focus groups were semi-structured and explored previous experiences of telerehabilitation, perceived benefits and challenges, and solutions to overcome these challenges. Focus groups were audio transcribed, and the service user transcript was translated into English. The resulting transcripts were analyzed using thematic analysis. RESULTS: Overall, participants were positive about the role of telerehabilitation but recommended hybrid delivery, with in-person rehabilitation in the early stages and telerehabilitation in the later stages. In relation to telerehabilitation in Ghana, there were 3 main themes: benefits, challenges or barriers, and implementation. Benefits included the convenience and lower cost for service users, the higher dose of therapy possible, and increased access for people in remote areas. However, challenges included lack of a stable internet connection, cost of phones and data packages, and low levels of literacy. Implementation issues included cultural relevance, information governance, and the platform used to deliver telerehabilitation, with most participants being familiar with WhatsApp. CONCLUSIONS: Telerehabilitation has the potential to be a useful method of delivering rehabilitation to people with neurological conditions in Ghana, especially in a hybrid rehabilitation model with telerehabilitation augmenting in-person sessions. However, many people were unaware of telerehabilitation, and challenges such as a reliable internet connection, cultural relevance, and costs need to be addressed. Clinical trials of low-cost telerehabilitation interventions contextualized to the specific user group are required.

Stroke occurrence by hypertension treatment status in Ghana and Nigeria: A case-control study.

BACKGROUND: Hypertension is preeminent among the vascular risk factors for stroke occurrence. The wide gaps in awareness, detection, treatment, and control rates of hypertension are fueling an epidemic of stroke in sub-Saharan Africa. PURPOSE: To quantify the contribution of untreated, treated but uncontrolled, and controlled hypertension to stroke occurrence in Ghana and Nigeria. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a case-control study across 16 study sites in Ghana and Nigeria. Cases were acute stroke (n = 3684) with age- and sex-matched stroke-free controls (n = 3684). We evaluated the associations of untreated hypertension, treated but uncontrolled hypertension, and controlled hypertension at BP of <140/90 mmHg with risk of stroke occurrence. We assessed the adjusted odds ratio and population-attributable risk of hypertension treatment control status associated with stroke occurrence. RESULTS: The frequencies of no hypertension, untreated hypertension, treated but uncontrolled hypertension and controlled hypertension among stroke cases were 4.0%, 47.7%, 37.1%, and 9.2% vs 40.7%, 34.9%, 15.9%, and 7.7% respectively among stroke-free controls, p < 0.0001. The aOR and PAR (95% CI) for untreated hypertension were 6.58 (5.15-8.41) and 35.4% (33.4-37.4); treated but uncontrolled hypertension was 9.95 (7.60-13.02) and 35.9% (34.2-37.5); and controlled hypertension 5.37 (3.90-7.41) and 8.5% (7.6-9.5) respectively. Untreated hypertension contributed a PAR of 47.5% to the occurrence of intracerebral hemorrhage vs 29.5% for ischemic stroke. The aOR of untreated hypertension for stroke occurrence was 13.31 (7.64-23.19) for <50 years; 7.14 (4.51-11.31) for 50-64 years; and 3.48 (2.28-5.30) for 65 years or more. CONCLUSION: The contribution of untreated hypertension and treated but uncontrolled hypertension to stroke occurrence among indigenous Africans is substantial. Implementing targeted interventions that address gaps in hypertension prevention and treatment, involving the local population, healthcare providers, and policymakers, can potentially substantially reduce the escalating burden of strokes in Africa.

ACHIEVE conference proceedings: implementing action plans to reduce and control hypertension burden in Africa.

The prevalence of hypertension, the commonest risk factor for preventable disability and premature deaths, is rapidly increasing in Africa. The African Control of Hypertension through Innovative Epidemiology, and a Vibrant Ecosystem [ACHIEVE] conference was convened to discuss and initiate the co-implementation of the strategic solutions to tame this burden toward achieving a target of 80% for awareness, treatment, and control by the year 2030. Experts, including the academia, policymakers, patients, the WHO, and representatives of various hypertension and cardiology societies generated a 12-item communique for implementation by the stakeholders of the ACHIEVE ecosystem at the continental, national, sub-national, and local (primary) healthcare levels.

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.

Epigenetics as a target to mitigate excess stroke risk in people of African ancestry: A scoping review.

BACKGROUND: Globally, individuals of African ancestry have a relatively greater stroke preponderance compared to other racial/ethnic groups. The higher prevalence of traditional stroke risk factors in this population, however, only partially explains this longstanding disparity. Epigenetic signatures are transgenerational and could be a plausible therapeutic target to further bend the stroke disparities curve for people of African ancestry. There is, however, limited data on epigenetics and stroke risk in this population. PURPOSE: To examine existing evidence and knowledge gaps on the potential contribution of epigenetics to excess stroke risk in people of African ancestry and avenues for mitigation. MATERIALS AND METHODS: We conducted a scoping review of studies published between January 2003 and July 2023, on epigenetics and stroke risk. We then summarized our findings, highlighting the results for people of African ancestry. RESULTS: Of 104 studies, there were only 6 studies that specifically looked at epigenetic mechanisms and stroke risk in people of African ancestry. Results of these studies show how patterns of DNA methylation and non-coding RNA interact with lifestyle choices, xenobiotics, and FVIII levels to raise stroke risk in people of African ancestry. However, no studies evaluated epigenetic patterns as actionable targets for the influence of psychosocial stressors or social context and excess stroke risk in this population (versus others). Also, no studies interrogated the role of established or novel therapeutic agents with the potential to reprogram DNA by adding or removing epigenetic markers in people of African ancestry. CONCLUSION: Epigenetics potentially offers a promising target for modifying the effects of lifestyle, environmental exposures, and other factors that differentially affect people of African ancestry and place them at relatively greater stroke risk compared to other populations. Studies that precisely assess the pathways by which epigenetic mechanisms modulate population-specific disparities in the risk of stroke are needed.