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.

Deciphering the contextual barriers to mainstreaming the implementation of stroke thrombolysis in a Ghanaian hospital: Findings from the activate mixed-methods study.

BACKGROUND: Each year, stroke-related death and disability claim over 143 million years of healthy life globally. Despite accounting for much of the global stroke burden, acute stroke care in Low-and-Middle-Income Countries remains suboptimal. Thrombolysis, an effective treatment option for stroke, is only received by a minority of stroke patients in these settings. AIM: To determine the context-specific barriers and facilitators for the implementation of mainstream stroke thrombolysis in a Ghanaian hospital. METHODS: We employed a mixed-methods approach involving key stakeholders (recipients, providers, and leaders) in the acute stroke care continuum. Surveys were administered to acute stroke patients, and in-depth key informant interviews were conducted with experts in stroke care, including a neurologist, medical director, neurology residents, a stroke nurse, emergency physicians, a radiologist, and a pharmacist. The data collected from these interviews were transcribed and analysed using content analysis with the CFIR (Consolidated Framework for Implementation Research) model as a guiding template. Two independent coders were involved in the analysis process to ensure reliability and accuracy. RESULTS: The stroke thrombolysis rate over a 6-month period was 0.83% (2 out of 242), with an average door-to-needle time among thrombolyzed patients being 2 hours, 37 minutes. Only 12.8% of patients (31 out of 242) presented within 4.5 hours of stroke symptom onset. The most significant obstacle to the implementation of acute stroke thrombolysis was related to the characteristics of the individuals involved, notably delays in presenting to the hospital among stroke patients due to a lack of knowledge about stroke symptoms and cultural beliefs. Additionally, a significant bottleneck that contributed to the discrepancy between the number of patients who presented within the 4.5-6 hour window and the number of patients who actually received thrombolysis was the inability to pay for the cost of thrombolytic agents. This was followed by challenges in the implementation processes. CONCLUSIONS: Addressing challenges related to stroke awareness, and financial constraints via multi-level stakeholder engagement, and enactment of stroke protocols are crucial steps in ensuring a successful implementation of a stroke thrombolysis program in a resource-limited setting.

Participation by patients from low- and middle-income countries (LMICs) in trial evidence supporting secondary stroke prevention guideline recommendations.

BACKGROUND: One out of every four strokes is a highly preventable recurrent stroke. However, while low-and-middle-income countries (LMICs) experience a disproportionate global burden of stroke, individuals in these regions seldomly participate in pivotal clinical trials, which form the basis for international expert consensus guideline recommendations. OBJECTIVE: To evaluate a contemporary and globally prominent expert consensus secondary stroke prevention guideline statement for the participation of clinical trial subjects recruited from LMICs in formulating key therapeutic recommendations. METHODS: We examined the 2021 American Heart Association/American Stroke Association Guideline for the Prevention of Stroke in Patients with Stroke and TIA. All randomized controlled trials (RCTs) cited in the Guideline were independently reviewed by two authors for study populations and participating countries with a focus on trials for vascular risk factor control and management by underlying stroke mechanism. We also reviewed all cited systematic reviews and meta-analyses for the original RCTs. RESULTS: Among 320 secondary stroke prevention clinical trials, 262 (82%) focused on vascular risk control addressing diabetes (n = 26), hypertension (n = 23), obstructive sleep apnea (n = 13), dyslipidaemia (n = 10), lifestyle (n = 188) and obesity (n = 2); and 58 focused on stroke mechanism management including atrial fibrillation (n = 10), large vessel atherosclerosis (n = 45) and small vessel disease (n = 3). Overall, 53 of 320 studies (16.6%) had contributions from LMICs ranging from 55.6% for dyslipidemia, 40.7% for diabetes, 26.1% for hypertension, 15.4% for OSA, 6.4% for lifestyle, 0% for obesity, and by mechanism: 60.0% for atrial fibrillation, 22.2% large vessel atherosclerosis and 33.3% for small vessel disease trials. Only 19 (5.9%) of the trials had participatory contributions from a country in sub-Saharan Africa (South Africa only). CONCLUSIONS: Compared to their global burden of stroke, LMICs are underrepresented in key clinical trials used in formulating a prominent global stroke prevention guideline. While current therapeutic recommendations are likely applicable to practice settings throughout the world, greater involvement of patients from LMIC settings will enhance the contextual relevance and generalizability of recommendations to these disparate populations.