DECODING STROKE DISPARITIES: ZIP CODES, COLOR CODES, AND EPIGENETIC CODES.

Despite decreases in overall stroke incidence and mortality in the United States, racial and ethnic disparities continue unabated. Of note, the long-standing disproportionate burden of stroke on African Americans compared to other racial and ethnic groups persists, and national projections indicate this toll will likely worsen over the next decade. Why have we not been able to bend the stroke disparities curve for African Americans? Well, this is mainly because traditional stroke risk factors, such as hypertension, diabetes, etc., account for just half of the Black vs. non-Hispanic White stroke disparity. As such, there is increasing interest in evaluating understudied factors like upstream social determinants of health, including geography, psychosocial stress, and environmental pollution; identifying potential mediators; and testing multilevel interventions to address them. This paper highlights emerging avenues that may help decode the excess stroke risk in African Americans, focusing on zip codes, color codes, and epigenetic codes.

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.

Forecasting the Economic Burden of Cardiovascular Disease and Stroke in the United States Through 2050: A Presidential Advisory From the American Heart Association.

BACKGROUND: Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment. METHODS: We used nationally representative health, economic, and demographic data to project health care costs attributable to key cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia) and conditions (coronary heart disease, stroke, heart failure, atrial fibrillation) through 2050. The human capital approach was used to estimate productivity losses from morbidity and premature mortality due to cardiovascular conditions. RESULTS: One in 3 US adults received care for a cardiovascular risk factor or condition in 2020. Annual inflation-adjusted (2022 US dollars) health care costs of cardiovascular risk factors are projected to triple between 2020 and 2050, from $400 billion to $1344 billion. For cardiovascular conditions, annual health care costs are projected to almost quadruple, from $393 billion to $1490 billion, and productivity losses are projected to increase by 54%, from $234 billion to $361 billion. Stroke is projected to account for the largest absolute increase in costs. Large relative increases among the Asian American population (497%) and Hispanic American population (489%) reflect the projected increases in the size of these populations. CONCLUSIONS: The economic burden of cardiovascular risk factors and overt cardiovascular disease in the United States is projected to increase substantially in the coming decades. Development and deployment of cost-effective programs and policies to promote cardiovascular health are urgently needed to rein in costs and to equitably enhance population health.

The link between insurance and blood pressure control in U.S. stroke survivors.

BACKGROUND: After a stroke, poorly controlled blood pressure (BP) is associated with a higher risk of recurrent vascular events. Despite the importance of controlling BP to avert recurrent vascular events, fewer than half of stroke survivors in the United States achieve BP control. It is unclear to what extent insurance status affects BP levels after stroke. METHODS: We assessed BP control among adults with a history of stroke who participated in the National Health and Nutrition Examination Surveys from 1999 through 2016. The relationship between insurance type and BP level (low normal: <120/80 mmHg and normal: <140/90 mmHg) were evaluated using logistic regression before and after adjusting for sociodemographic characteristics and medical comorbidities for those <65 years and ≥ 65 years. RESULTS: Among 1646 adult stroke survivors (weighted n = 5,586,417), 30% had BP in the low normal range while 64% had BP in the normal range. Among 613 stroke survivors <65 years (weighted n = 2,396,980), only those with other government insurance (CHAMPVA, CHAMPUS/TRICARE) had better BP control than the uninsured (adjusted HR 2.68, 95% CI 0.99-7.25). Among 1033 participants ≥65 years (weighted n = 3,189,437), those with private insurance plus Medicare trended toward better normal BP compared to Medicare alone (adjusted HR 1.34, 95% CI 0.94-1.90). CONCLUSIONS: Only stroke survivors with CHAMPVA, CHAMPUS/TRICARE government insurance in the United States have lower odds of controlled BP compared to no insurance among those <65 years. Insurance alone does not improve BP control among stroke survivors.

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.

Brain imaging prior to thrombectomy in the late window of large vessel occlusion ischemic stroke: a systematic review and meta-analysis.

PURPOSE: Optimal imaging modalities to select patients for endovascular thrombectomy (EVT) in the late window of acute ischemic stroke due to large vessel occlusions (AIS-LVO) are not known. We conducted a systematic review comparing outcomes of patients selected by non-contrast computed tomography (NCCT)/CT angiography (CTA) vs. those selected by CT perfusion (CTP) or magnetic resonance imaging (MRI) for EVT in these patients. METHODS: We searched PUBMED, EMBASE, and the Cochrane Library from January 1, 2000, to July 15, 2023, to identify studies comparing outcomes of patients selected for EVT by NCCT/CTA vs. CTP or MRI in the late time window for AIS-LVO. Primary outcome was independence (mRS 0-2) at 90 days or discharge. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. We pooled data across studies based on an inverse variance method. RESULTS: Six cohort studies with 4208 patients were included. Pooled results showed no significant difference in the rate of independence at 90 days or discharge (RR 0.96, 95% CI 0.88-1.03) and sICH (RR 1.26, 0.85-1.86) between patients selected by NCCT/CTA vs. CTP or MRI for EVT in the late window of AIS-LVO. However, patients selected by NCCT/CTA vs. CTP or MRI for EVT were associated with a higher risk of mortality (RR 1.21, 1.06-1.39). CONCLUSION: For AIS-LVO in the late window, patients selected by NCCT/CTA compared with those selected by CTP or MRI for EVT might have a comparable rate of functional independence and sICH. Baseline NCCT/CTA may triage AIS-LVO in the late window.

Addressing disparities in the global epidemiology of stroke.

Stroke is the second leading cause of death and the third leading cause of disability worldwide. Though the burden of stroke worldwide seems to have declined in the past three decades, much of this effect reflects decreases in high-income countries (HICs). By contrast, the burden of stroke has grown rapidly in low-income and middle-income countries (LMICs), where epidemiological, socioeconomic and demographic shifts have increased the incidence of stroke and other non-communicable diseases. Furthermore, even in HICs, disparities in stroke epidemiology exist along racial, ethnic, socioeconomic and geographical lines. In this Review, we highlight the under-acknowledged disparities in the burden of stroke. We emphasize the shifting global landscape of stroke risk factors, critical gaps in stroke service delivery, and the need for a more granular analysis of the burden of stroke within and between LMICs and HICs to guide context-appropriate capacity-building. Finally, we review strategies for addressing key inequalities in stroke epidemiology, including improvements in epidemiological surveillance and context-specific research efforts in under-resourced regions, development of the global workforce of stroke care providers, expansion of access to preventive and treatment services through mobile and telehealth platforms, and scaling up of evidence-based strategies and policies that target local, national, regional and global stroke disparities.

Dietary patterns associated with hypertension among stroke-free indigenous Africans: insights from the Stroke Investigative Research and Educational Network study.

BACKGROUND: The dietary factors associated with the high burden of hypertension among indigenous Africans remain poorly understood. We assessed the relationship between dietary patterns and hypertension among indigenous Africans. METHOD: In this study, 1550 participants with hypertension matched (for age: ±â€Š5 years, sex and ethnicity) with 1550 participants without hypertension were identified from the stroke-free population in the Stroke Investigative Research and Educational Network study in Ghana and Nigeria. Food consumption was assessed using a food frequency questionnaire, and dietary information was summarized using principal component analysis to identify seven dietary patterns. Conditional logistic regression was applied to compute the odds ratio (OR) and 95% confidence interval (CI) for the risk of hypertension by tertiles of dietary patterns adjusting for age, education, income, smoking, alcohol use, physical inactivity, family history of cardiovascular diseases, obesity and salt intake at a two-sided P less than 0.05. RESULTS: Multivariable-adjusted OR [95% confidence interval (CI)] for risk of hypertension by second and third tertiles [using the lowest (first) tertile as reference] of dietary patterns were 0.62 (0.48-0.80), 0.70 (0.54-0.90) for whole grains and fruit drinks; 0.87 (0.68-1.12), 0.83 (0.64-1.08) for fruits; 0.85 (0.65-1.10), 0.97 (0.75-1.26) for vegetables, legumes and potatoes; 0.78 (0.60-1.00), 0.84 (0.65-1.08) for fried foods and sweetened drinks; 1.13 (0.88-1.45), 0.80 (0.62-1.03) for poultry product and organ meat; 1.11 (0.86-1.43), 0.88 (0.68-1.14) for red meat; and 1.14 (0.88-1.48), 1.09 (0.84-1.43) for processed foods ( P  < 0.05). CONCLUSION: A higher adherence to dietary consumption of whole grains and fruits was inversely associated with low odds of hypertension in this population.

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.

Factors associated with frequency of fruit and vegetable consumption among selected sub-Saharan African populations: evidence from the Cardiovascular H3Africa Innovation Resource Project.

BACKGROUND: Frequent fruit and vegetable consumption is considered a promising dietary behaviour that protects health. However, most existing studies about the factors associated with this phenomenon among Africans are based on single-country reports, apart from one meta-regression combining smaller studies. This study harmonized large datasets and assessed factors associated with the frequency of fruit and vegetable consumption in this population. METHODS: Individual-level data on sociodemographics, lifestyle and diet from 20 443 participants across five African countries (Burkina Faso, Ghana, Kenya, South Africa and Nigeria), from the Stroke Investigative Research and Educational Network (SIREN) and Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) studies, were harmonized. Total frequency of fruit and vegetable consumption (in portions/week) was classified as 'low' (≤6), 'moderate' (7-14) and 'high' (≥15). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with the total frequency of fruit and vegetable consumption (using 'low' consumption as the reference) were estimated using multinomial regression models. RESULTS: Mean age of participants was 54.3 ± 11.8 years, 10 641 (52.1%) were female, and the median (interquartile range) frequency of total fruit and vegetable consumption was 10.0 (4.0, 21.0) portions/week. Participants with a family history of cardiovascular disease [moderate (aOR, 0.92; 95% CI, 0.85, 1.00) and high (aOR, 0.85; 95% CI, 0.78, 0.92)], current smokers [moderate (aOR, 0.83; 95% CI, 0.74, 0.94) and high (aOR, 0.78; 95% CI, 0.69, 0.88)], current alcohol users [moderate (aOR, 0.92; 95% CI, 0.85, 1.00) and high (aOR, 0.82; 95% CI, 0.76, 0.89)] and physically inactive participants [moderate (aOR, 0.85; 95% CI, 0.75, 0.96) and high (aOR, 0.80; 95% CI, 0.70, 0.90)] were less likely to consume fruits and vegetables frequently. CONCLUSION: Africans with lifestyle risk factors for cardiovascular disease were less likely to consume fruit and vegetables frequently.

Frequency & factors associated with elevated lipoprotein-a among Ghanaian stroke survivors.

BACKGROUND: Indigenous Africans are genetically predisposed to elevated lipoprotein-a (Lp(a)), a veritable risk factor for ischemic stroke. Recent studies have demonstrated the promising efficacy of therapeutic interventions for addressing elevated Lp(a) among patients at high risk of atherosclerotic cardiovascular events. It is important to assess the burden of elevated Lp(a) among stroke survivors of African ancestry aimed at addressing potential unmet therapeutic gaps for optimal secondary prevention. PURPOSE: To assess the frequency of elevated lipoprotein-a among Ghanaian stroke survivors and factors associated with it. METHODS: A prospective study conducted at the Neurology clinic of the Komfo Anokye Teaching Hospital among ischemic stroke survivors aged ≥18 years. Serum lipoprotein-a concentrations were measured using ELISA kits. A multivariate regression analysis was fitted to identify factors independently associated with elevated lipoprotein-a concentration > 30 mg/dl. RESULTS: Among 116 stroke survivors, 35 (30.2%) had elevated Lp(a). The adjusted odds ratio (95% CI) of factors associated with elevated Lp(a) were female sex 3.09 (1.05-9.12), p = 0.04, diabetes mellitus 3.52 (1.32-9.40), p = 0.01, urban dwelling 4.64 (1.61-13.39), p = 0.005 and total cholesterol 1.85 (1.28-2.67), p = 0.001. Whereas the LDL cholesterol significantly decreased from baseline to month 12 among a subset of participants, the Lp(a) levels significantly increased from a baseline value of 29.38 ± 15.32 mg/dl to 40.97 ± 29.72 mg/dl, p = 0.032. CONCLUSION: Approximately 1 in 3 Ghanaian ischemic stroke survivors harbor an elevated Lp(a) associated with female sex, urban residence, diabetes mellitus and raised cholesterol. This burden highlights an unmet therapeutic gap in secondary risk reduction in this resource-limited setting.