Risk Factor Characterization of Ischemic Stroke Subtypes Among West Africans.

BACKGROUND AND PURPOSE: To identify the qualitative and quantitative contributions of conventional risk factors for occurrence of ischemic stroke and its key pathophysiologic subtypes among West Africans. METHODS: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with ischemic stroke who were etiologically subtyped using the A-S-C-O-D classification into atherosclerosis, small-vessel occlusion, cardiac pathology, other causes, and dissection. Controls were age- and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle, and psychosocial factors were performed. We used conditional logistic regression to estimate adjusted odds ratios with 95% CI. RESULTS: There were 2431 ischemic stroke case and stroke-free control pairs with respective mean ages of 62.2±14.0 versus 60.9±13.7 years. There were 1024 (42.1%) small vessel occlusions, 427 (17.6%) large-artery atherosclerosis, 258 (10.6%) cardio-embolic, 3 (0.1%) carotid dissections, and 719 (29.6%) undetermined/other causes. The adjusted odds ratio (95% CI) for the 8 dominant risk factors for ischemic stroke were hypertension, 10.34 (6.91-15.45); dyslipidemia, 5.16 (3.78-7.03); diabetes, 3.44 (2.60-4.56); low green vegetable consumption, 1.89 (1.45-2.46); red meat consumption, 1.89 (1.45-2.46); cardiac disease, 1.88 (1.22-2.90); monthly income $100 or more, 1.72 (1.24-2.39); and psychosocial stress, 1.62 (1.18-2.21). Hypertension, dyslipidemia, diabetes were confluent factors shared by small-vessel, large-vessel and cardio-embolic subtypes. Stroke cases and stroke-free controls had a mean of 5.3±1.5 versus 3.2±1.0 adverse cardio-metabolic risk factors respectively (P<0.0001). CONCLUSIONS: Traditional vascular risk factors demonstrate important differential effect sizes with pathophysiologic, clinical and preventative implications on the occurrence of ischemic stroke among indigenous West Africans.

Disparities in clinical features and outcomes of peripartum cardiomyopathy in high versus low prevalent regions in Nigeria.

AIMS: The prospective, multicentre Peripartum Cardiomyopathy in Nigeria (PEACE) registry originally demonstrated a high prevalence of peripartum cardiomyopathy (PPCM) among patients originating from Kano, North-West Nigeria. In a post hoc analysis, we sought to determine if this phenomenon was characterized by a differential case profile and outcome among PPCM cases originating elsewhere. METHODS AND RESULTS: Overall, 199 (81.6%) of a total 244 PPCM patients were recruited from three sites in Kano, compared with 45 patients (18.4%) from 11 widely dispersed centres across Nigeria. Presence and extent of ventricular myocardial remodelling during follow-up, relative to baseline status, were assessed by echocardiography. During median 17 months follow-up, Kano patients demonstrated significantly better myocardial reverse remodelling than patients from other sites. Overall, 50.6% of patients from Kano versus 28.6% from other regions were asymptomatic (P = 0.029) at study completion, with an accompanying difference in all-cause mortality (17.6% vs. 22.2% respectively, P = 0.523) not reaching statistical significance. Alternatively, 135/191 (84.9%) of Kano patients had selenium deficiency (<70 µg/L), and 46/135 (34.1%) of them received oral selenium supplementation. Critically, those that received selenium supplementation demonstrated better survival (6.5% vs. 21.2%; P = 0.025), but the supplement did not have significant impact on myocardial remodelling. CONCLUSIONS: This study has shown important non-racial regional disparities in the clinical features and outcomes of PPCM patients in Nigeria, that might partly be explained by selenium supplementation.

Clinical Features and Outcomes of Peripartum Cardiomyopathy in Nigeria.

BACKGROUND: Nigeria has the highest incidence of peripartum cardiomyopathy (PPCM) in the world. However, data on PPCM-related outcomes are limited. OBJECTIVES: The purpose of this study was to examine the clinical profile, myocardial remodeling, and survival of patients with PPCM in Nigeria. METHODS: This study consecutively recruited 244 PPCM patients (median 7 months postpartum) at 14 sites in Nigeria and applied structured follow-up for a median of 17 months (interquartile range: 14 to 20 months). Left ventricular reverse remodeling (LVRR) was defined as the composite of left ventricular (LV) end-diastolic dimension <33 mm/m2 and absolute increase in left ventricular ejection fraction (LVEF) ≥10%. LV full recovery was defined as LVEF ≥55%. RESULTS: Overall, 45 (18.7%) patients died during follow-up. Maternal age <20 years (hazard ratio [HR]: 2.40; 95% confidence interval (CI): 1.27 to 4.54), hypotension (HR: 1.87; 95% CI: 1.02 to 3.43), tachycardia (HR: 2.38; 95% CI: 1.05 to 5.43), and LVEF <25% at baseline (HR: 2.11; 95% CI: 1.12 to 3.95) independently predicted mortality. Obesity (HR: 0.16; 95% CI: 0.04 to 0.55) and regular use of beta-blockers at 6-month follow-up (HR: 0.20; 95% CI: 0.09 to 0.41) were independently associated with reduced risk for mortality. In total, 48 patients (24.1%) achieved LVRR and 45 (22.6%) achieved LV full recovery. LVEF <25% at baseline (HR: 0.66; 95% CI: 0.47 to 0.92) and regular use of beta-blockers at 6-month follow-up (HR: 1.62; 95% CI: 1.17 to 2.25) independently determined the risk for LV full recovery. Progressive reverse remodeling of all cardiac chambers was observed. In total, 18 patients (7.4%) were hospitalized during the study. CONCLUSIONS: This is the largest study of PPCM in Africa. Consistent with late presentations, the mortality rate was high, whereas frequencies of LVRR and LV full recovery were low. Several variables predicted poor outcomes, and regular use of beta-blockers correlated with late survival and LV functional recovery.

Unraveling the risk factors for spontaneous intracerebral hemorrhage among West Africans.

OBJECTIVE: To characterize risk factors for spontaneous intracerebral hemorrhage (sICH) occurrence and severity among West Africans. METHODS: The Stroke Investigative Research and Educational Network (SIREN) study is a multicenter case-control study involving 15 sites in Ghana and Nigeria. Patients were adults ≥18 years old with CT-confirmed sICH with age-, sex-, and ethnicity-matched stroke-free community controls. Standard instruments were used to assess vascular, lifestyle, and psychosocial factors. Factors associated with sICH and its severity were assessed using conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% confidence intervals (CIs) for factors. RESULTS: Of 2,944 adjudicated stroke cases, 854 were intracerebral hemorrhage (ICH). Mean age of patients with ICH was 54.7 ± 13.9 years, with a male preponderance (63.1%), and 77.3% were nonlobar. Etiologic subtypes of sICH included hypertension (80.9%), structural vascular anomalies (4.0%), cerebral amyloid angiopathy (0.7%), systemic illnesses (0.5%), medication-related (0.4%), and undetermined (13.7%). Eight factors independently associated with sICH occurrence by decreasing order of PAR with their adjusted OR (95% CI) were hypertension, 66.63 (20.78-213.72); dyslipidemia, 2.95 (1.84-4.74); meat consumption, 1.55 (1.01-2.38); family history of CVD, 2.22 (1.41-3.50); nonconsumption of green vegetables, 3.61 (2.07-6.31); diabetes mellitus, 2.11 (1.29-3.46); stress, 1.68 (1.03-2.77); and current tobacco use, 14.27 (2.09-97.47). Factors associated with severe sICH using an NIH Stroke Scale score >15 with adjusted OR (95% CI) were nonconsumption of leafy green vegetables, 2.03 (1.43-2.88); systolic blood pressure for each mm Hg rise, 1.01 (1.00-1.01); presence of midline shift, 1.54 (1.11-2.13); lobar ICH, 1.72 (1.16-2.55); and supratentorial bleeds, 2.17 (1.06-4.46). CONCLUSIONS: Population-level control of the dominant factors will substantially mitigate the burden of sICH in West Africa.

Knowledge, attitudes and practices of West Africans on genetic studies of stroke: Evidence from the SIREN Study.

BACKGROUND: It is crucial to assess genomic literacy related to stroke among Africans in preparation for the ethical, legal and societal implications of the genetic revolution which has begun in Africa. OBJECTIVE: To assess the knowledge, attitudes and practices (KAP) of West Africans about stroke genetic studies. METHODS: A comparative cross-sectional study was conducted among stroke patients and stroke-free controls recruited across 15 sites in Ghana and Nigeria. Participants' knowledge of heritability of stroke, willingness to undergo genetic testing and perception of the potential benefits of stroke genetic research were assessed using interviewer-administered questionnaire. Descriptive, frequency distribution and multiple regression analyses were performed. RESULTS: Only 49% of 2029 stroke patients and 57% of 2603 stroke-free individuals knew that stroke was a heritable disorder. Among those who knew, 90% were willing to undergo genetic testing. Knowledge of stroke heritability was associated with having at least post-secondary education (OR 1.51, 1.25-1.81) and a family history of stroke (OR 1.20, 1.03-1.39) while Islamic religion (OR=0.82, CI: 0.72-0.94), being currently unmarried (OR = 0.81, CI: 0.70-0.92), and alcohol use (OR = 0.78, CI: 0.67-0.91) were associated with lower odds of awareness of stroke as a heritable disorder. Willingness to undergo genetic testing for stroke was associated with having a family history of stroke (OR 1.34, 1.03-1.74) but inversely associated with a medical history of high blood pressure (OR = 0.79, 0.65-0.96). CONCLUSION: To further improve knowledge of stroke heritability and willingness to embrace genetic testing for stroke, individuals with less formal education, history of high blood pressure and no family history of stroke require targeted interventions.

Knowledge, attitudes and practices related to stroke in Ghana and Nigeria: A SIREN call to action.

INTRODUCTION: Stroke is a prominent cause of death, disability, and dementia in sub-Saharan Africa (SSA). The Stroke Investigative Research and Education Network works collaboratively with stroke survivors and individuals serving as community controls to comprehensively characterize the genomic, sociocultural, economic and behavioral risk factors for stroke in SSA. PURPOSE: In this paper, we aim to: i) explore the attitudes, beliefs, and practices related to stroke in Ghana and Nigeria using the process of qualitative description; and ii) propose actions for future research and community-based participation and education. METHODS: Stroke survivors, their caregivers, health care professionals, and community representatives and faith-based leaders participated in one of twenty-six focus groups, which qualitatively explored community beliefs, attitudes and practices related to stroke in Ghana and Nigeria. Arthur Kleinman's Explanatory Model of Illness and the Social Ecological Model guided the questions and/or thematic analysis of the qualitative data. We hereby describe our focus group methods and analyses of qualitative data, as well as the findings and suggestions for improving stroke outcomes. RESULTS AND DISCUSSION: The major findings illustrate the fears, causes, chief problems, treatment, and recommendations related to stroke through the views of the participants, as well as recommendations for working effectively with the SIREN communities. Findings are compared to SIREN quantitative data and other qualitative studies in Africa. As far as we are aware, this is the first paper to qualitatively explore and contrast community beliefs, attitudes, and practices among stroke survivors and their caregivers, community and faith-based leaders, and health professionals in multiple communities within Nigeria and Ghana.

Exploring Overlaps Between the Genomic and Environmental Determinants of LVH and Stroke: A Multicenter Study in West Africa.

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. OBJECTIVES: 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 SIREN (Stroke Investigative Research and Education Network) study. METHODS: SIREN is a transnational, multicenter study involving acute stroke patients and age-, ethnicity-, and sex-matched control subjects 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% male). Fifty-five 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 blood pressure (167.1/99.5 mm Hg vs 151.7/90.6 mm Hg; p < 0.001). Uncontrolled blood pressure 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 (adjusted odds ratio [AOR]: 1.91; 95% confidence interval [CI]: 1.14 to 3.19), female sex (AOR: 2.01; 95% CI: 1.44 to 2.81), and diastolic blood pressure > 90 mm Hg (AOR: 2.10; 95% CI: 1.39 to 3.19; p < 0.001). CONCLUSIONS: 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 LVH 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.

Prevalence and Prognostic Features of ECG Abnormalities in Acute Stroke: Findings From the SIREN Study Among Africans.

BACKGROUND: Africa has a growing burden of stroke with associated high morbidity and a 3-year fatality rate of 84%. Cardiac disease contributes to stroke occurrence and outcomes, but the precise relationship of abnormalities as noted on a cheap and widely available test, the electrocardiogram (ECG), and acute stroke outcomes have not been previously characterized in Africans. OBJECTIVES: The study assessed the prevalence and prognoses of various ECG abnormalities among African acute stroke patients encountered in a multisite, cross-national epidemiologic study. METHODS: We included 890 patients from Nigeria and Ghana with acute stroke who had 12-lead ECG recording within first 24 h of admission and stroke classified based on brain computed tomography scan or magnetic resonance imaging. Stroke severity at baseline was assessed using the Stroke Levity Scale (SLS), whereas 1-month outcome was assessed using the modified Rankin Scale (mRS). RESULTS: Patients' mean age was 58.4 ± 13.4 years, 490 were men (55%) and 400 were women (45%), 65.5% had ischemic stroke, and 85.4% had at least 1 ECG abnormality. Women were significantly more likely to have atrial fibrillation, or left ventricular hypertrophy with or without strain pattern. Compared to ischemic stroke patients, hemorrhagic stroke patients were less likely to have atrial fibrillation (1.0% vs. 6.7%; p = 0.002), but more likely to have left ventricular hypertrophy (64.4% vs. 51.4%; p = 0.004). Odds of severe disability or death at 1 month were higher with severe stroke (AOR: 2.25; 95% confidence interval: 1.44 to 3.50), or atrial enlargement (AOR: 1.45; 95% confidence interval: 1.04 to 2.02). CONCLUSIONS: About 4 in 5 acute stroke patients in this African cohort had evidence of a baseline ECG abnormality, but presence of any atrial enlargement was the only independent ECG predictor of death or disability.

Stroke Investigative Research and Education Network: Community Engagement and Outreach Within Phenomics Core.

Stroke is the leading cause of neurological hospital admissions in sub-Saharan Africa (SSA) and the second leading cause of death globally. The Stroke Investigative Research and Education Network seeks to comprehensively characterize the genomic, sociocultural, economic, and behavioral risk factors for stroke and to build effective teams for research to address and decrease the burden of stroke and other noncommunicable diseases in SSA. One of the first steps to address this goal is to effectively engage the communities that suffer the high burden of disease. The purpose of this article is to describe plans to elucidate information about knowledge, attitudes, beliefs, and practices about stroke and genomics from patients, caregivers, and local leaders, to recruit participation in research activities and dissemination of ongoing results, as well as to facilitate research uptake and impact within the broader communities of scientists, health professionals, policy makers, and others. We describe the (a) study sites and their communities; (b) plans for community advisory boards, focus groups, and surveys; (c) methods for data management in REDCap database; (d) analyses of qualitative data; (e) evaluation of community and public engagement across multiple sites and research teams in SSA and the United States; (f) use of RE-AIM for presentation of evaluation data; and (g) community indicators of success. This is the first of its kind public outreach engagement initiative to evaluate stroke and genomics in SSA, and has implications as a model for assessment in other high-stroke risk populations.