Non-cigarette tobacco use and stroke among West Africans: evidence from the SIREN study.

INTRODUCTION: Non-cigarette tobacco (NCT) represents a form of tobacco use with a misperceived significance in chronic disease events. Whether NCT use is sufficient to promote stroke events, especially among Africans, is yet to be understood. This study assessed the relationship between NCT use and stroke among indigenous Africans. METHODS: A total of 7,617 respondents (NCT users: 41 vs. non-NCT: 7576) from the Stroke Investigation Research and Educational Network study were included in the current analysis. NCT use was defined as self-reported use of smoked (cigars or piper) or smokeless (snuff or chewed) tobacco in the past year preceding stroke events. Stroke was defined based on clinical presentation and confirmed with a cranial CT/MRI. Multivariable-adjusted logistic regression was applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for the relationship between NCT and stroke at p<0.05. RESULTS: Out of the 41 (0.54%) who reported NCT use, 27 (65.9%) reported using smokeless NCT. NCT users were older than non-smokers (62.8±15.7 vs 57.7±14.8 years). Overall, NCT use was associated with first-ever stroke (OR: 2.08; 95%CI: 1.02, 4.23) in the entire sample. Notably, smokeless NCT use was independently associated with higher odds of stroke (OR: 2.74; 95%CI: 1.15, 6.54), but smoked NCT use (OR: 0.16; 95%CI: 0.02, 1.63) presented a statistically insignificant association after adjusting for hypertension and other covariates. CONCLUSIONS: NCT use was associated with higher odds of stroke, and public health interventions targeting NCT use might be promising in reducing the burden of stroke among indigenous Africans. IMPLICATIONS: A detailed understanding of the relationship between NCT use and stroke will likely inform well-articulated policy guidance to promote evidence-based recommendations for public health prevention and management of stroke on the African continent.

Are there differences in perceptions, preferences and attitudes towards disclosure of genetic testing for Stroke? A qualitative study among stroke-free SIREN-SIBS genomics study participants.

OBJECTIVE: This study explored perceptions, preferences and attitudes towards disclosure of genetic testing results for stroke among stroke-free controls (and their family members) in the SIREN-SIBS Genomics Study, healthcare providers and policymakers. MATERIALS AND METHODS: We conducted a qualitative thematic analysis of key informant interviews with 61 participants recruited from community advisory boards (30) and health care providers (31) across seven sites in Nigeria and Ghana. RESULTS: Major findings illustrate differences in the knowledge of genetic testing with superior knowledge among health care professionals. Relatives and religious leaders were opined as the best to receive the disclosure as they would be able to break the news to the patient in a culturally sensitive manner to reduce the likely resultant emotional outburst. Poor level of awareness of national guidelines for disclosing genetic results exist. Key facilitating factors for disclosure are education, enabling environment, involvement of religious and community leaders, campaigns, and possible treatment options. Disclosure inhibitors include inadequate information, fear of marital break-up or family displacement, fear of stigmatization, fear of isolation, religious beliefs, health worker attitude, and lack of preparedness to accept results. CONCLUSIONS: These necessitate culturally sensitive interventions for continuing education, increased awareness and sustained engagement to equip all stakeholders in genetic testing disclosure process.

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.

Differential associations between pre-diabetes, diabetes and stroke occurrence among West Africans.

BACKGROUND: There are limited data from Africa on the burden and associations between pre-diabetes (pre-DM), diabetes mellitus (DM) and stroke occurrence in a region experiencing a profound rise in stroke burden. PURPOSE: To characterize the associations between stroke and dysglycemic status among West Africans. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with clinical and radiological evidence of an acute stroke. Controls were age-and-gender matched stroke-free adults. Detailed evaluations for vascular factors were performed. Pre-diabetes was defined as HBA1c of 5.7%-6.4% or Fasting blood glucose (FBG) 5.6-7.0 mmol/L and DM as HBA1c >6.5% or FBG>7.0 mmol/L. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. RESULTS: Among 2,935 stroke cases the mean age was 60.0 ± 14.2 years with 55.2% being males. By glycemic status, 931 (31.7%) were euglycemic, 633 (21.6%) had Pre-diabetes and 1371 (46.7%) had DM. Of the age- and sex-matched stroke-free controls 69.2% were euglycemic, 13.3% had pre-DM and 17.5% had DM. Pre-DM [aOR (95% CI): 3.68(2.61-5.21)] and DM [4.29 (3.19-5.74)] were independently associated with stroke. The aOR of Pre-DM for ischemic stroke 3.06 (2.01-4.64)] was lower than 4.82 (3.37-6.89) for DM. However, the aOR of Pre-DM for hemorrhagic stroke 6.81 (95% CI: 3.29 - 14.08)] was higher than 3.36 (1.94-5.86) for DM. Furthermore, the aOR of pre-DM for ischemic stroke subtypes were 9.64 (1.30-71.57) for cardio-embolic stroke, 3.64 (1.80-7.34) for small-vessel occlusive disease and 4.63 (0.80-26.65) for large-vessel disease. CONCLUSION: Pre-DM is strongly and independently associated with stroke in Africans. Improving glycemic control through screening, healthy lifestyle and pharmacotherapy at a population level may be strategic in reducing the rising burden of stroke in Africa.

A Novel Afrocentric Stroke Risk Assessment Score: Models from the Siren Study.

BACKGROUND: Stroke risk can be quantified using risk factors whose effect sizes vary by geography and race. No stroke risk assessment tool exists to estimate aggregate stroke risk for indigenous African. OBJECTIVES: To develop Afrocentric risk-scoring models for stroke occurrence. MATERIALS AND METHODS: We evaluated 3533 radiologically confirmed West African stroke cases paired 1:1 with age-, and sex-matched stroke-free controls in the SIREN study. The 7,066 subjects were randomly split into a training and testing set at the ratio of 85:15. Conditional logistic regression models were constructed by including 17 putative factors linked to stroke occurrence using the training set. Significant risk factors were assigned constant and standardized statistical weights based on regression coefficients (ß) to develop an additive risk scoring system on a scale of 0-100%. Using the testing set, Receiver Operating Characteristics (ROC) curves were constructed to obtain a total score to serve as cut-off to discriminate between cases and controls. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at this cut-off. RESULTS: For stroke occurrence, we identified 15 traditional vascular factors. Cohen's kappa for validity was maximal at a total risk score of 56% using both statistical weighting approaches to risk quantification and in both datasets. The risk score had a predictive accuracy of 76% (95%CI: 74-79%), sensitivity of 80.3%, specificity of 63.0%, PPV of 68.5% and NPV of 76.2% in the test dataset. For ischemic strokes, 12 risk factors had predictive accuracy of 78% (95%CI: 74-81%). For hemorrhagic strokes, 7 factors had a predictive accuracy of 79% (95%CI: 73-84%). CONCLUSIONS: The SIREN models quantify aggregate stroke risk in indigenous West Africans with good accuracy. Prospective studies are needed to validate this instrument for stroke prevention.

The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project.

BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18-60.5 months). Young-onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per-capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub-Saharan Africa. The registry will serve as a platform for development of multipronged evidence-based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria. © 2020 International Parkinson and Movement Disorder Society.

Differential Impact of Risk Factors on Stroke Occurrence Among Men Versus Women in West Africa.

Background and Purpose- The interplay between sex and the dominant risk factors for stroke occurrence in sub-Saharan Africa has not been clearly delineated. We compared the effect sizes of risk factors of stroke by sex among West Africans. Methods- SIREN study (Stroke Investigative Research and Educational Networks) is a case-control study conducted at 15 sites in Ghana and Nigeria. Cases were adults aged >18 years with computerized tomography/magnetic resonance imaging confirmed stroke, and controls were age- and sex-matched stroke-free adults. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed using validated tools. We used conditional logistic regression to estimate odds ratios and reported risk factor specific and composite population attributable risks with 95% CIs. Results- Of the 2118 stroke cases, 1193 (56.3%) were males. The mean±SD age of males was 58.1±13.2 versus 60.15±14.53 years among females. Shared modifiable risk factors for stroke with adjusted odds ratios (95% CI) among females versus males, respectively, were hypertension [29.95 (12.49-71.77) versus 16.1 0(9.19-28.19)], dyslipidemia [2.08 (1.42-3.06) versus 1.83 (1.29-2.59)], diabetes mellitus [3.18 (2.11-4.78) versus 2.19 (1.53-3.15)], stress [2.34 (1.48-3.67) versus 1.61 (1.07-2.43)], and low consumption of green leafy vegetables [2.92 (1.89-4.50) versus 2.00 (1.33-3.00)]. However, salt intake and income were significantly different between males and females. Six modifiable factors had a combined population attributable risk of 99.1% (98.3%-99.6%) among females with 9 factors accounting for 97.2% (94.9%-98.7%) among males. Hemorrhagic stroke was more common among males (36.0%) than among females (27.6%), but stroke was less severe among males than females. Conclusions- Overall, risk factors for stroke occurrence are commonly shared by both sexes in West Africa favoring concerted interventions for stroke prevention in the region.

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke.

BACKGROUND: Annotation and Image Markup on ClearCanvas Enriched Stroke-phenotyping Software (ACCESS) is a novel stand-alone computer software application that allows the creation of simple standardized annotations for reporting brain images of all stroke types. We developed the ACCESS application and determined its inter-rater and intra-rater reliability in the Stroke Investigative Research and Educational Network (SIREN) study to assess its suitability for multicenter studies. METHODS: One hundred randomly selected stroke imaging reports from 5 SIREN sites were re-evaluated by 4 trained independent raters to determine the inter-rater reliability of the ACCESS (version 12.0) software for stroke phenotyping. To determine intra-rater reliability, 6 raters reviewed the same cases previously reported by them after a month of interval. Ischemic stroke was classified using the Oxfordshire Community Stroke Project (OCSP), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and Atherosclerosis, Small-vessel disease, Cardiac source, Other cause (ASCO) protocols, while hemorrhagic stroke was classified using the Structural lesion, Medication, Amyloid angiopathy, Systemic disease, Hypertensive angiopathy and Undetermined (SMASH-U) protocol in ACCESS. Agreement among raters was measured with Cohen's kappa statistics. RESULTS: For primary stroke type, inter-rater agreement was .98 (95% confidence interval [CI], .94-1.00), while intra-rater agreement was 1.00 (95% CI, 1.00). For OCSP subtypes, inter-rater agreement was .97 (95% CI, .92-1.00) for the partial anterior circulation infarcts, .92 (95% CI, .76-1.00) for the total anterior circulation infarcts, and excellent for both lacunar infarcts and posterior circulation infarcts. Intra-rater agreement was .97 (.90-1.00), while inter-rater agreement was .93 (95% CI, .84-1.00) for TOAST subtypes. Inter-rater agreement ranged between .78 (cardioembolic) and .91 (large artery atherosclerotic) for ASCO subtypes and was .80 (95% CI, .56-1.00) for SMASH-U subtypes. CONCLUSION: The ACCESS application facilitates a concordant and reproducible classification of stroke subtypes by multiple investigators, making it suitable for clinical use and multicenter research.

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.

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.

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.

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.

Clinical and neuroimaging factors associated with 30-day fatality among indigenous West Africans with spontaneous intracerebral hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with a high case fatality rate in resource-limited settings. The independent predictors of poor outcome after ICH in sub-Saharan Africa remains to be characterized in large epidemiological studies. We aimed to determine factors associated with 30-day fatality among West African patients with ICH. METHODS: The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study conducted at 15 sites in Nigeria and Ghana. Adults aged ≥18 years with spontaneous ICH confirmed with neuroimaging. Demographic, cardiovascular risk factors, clinical features and neuroimaging markers of severity were assessed. The independent risk factors for 30-day mortality were determined using a multivariate logistic regression analysis with an adjusted odds ratio (OR) and 95% confidence interval (CI). RESULTS: Among 964 patients with ICH, 590 (61.2%) were males with a mean age (SD) of 54.3(13.6) years and a case fatality of 34.3%. Factors associated with 30-day mortality among ICH patients include: Elevated mean National Institute of Health Stroke Scale(mNIHSS);(OR 1.06; 95% CI 1.02-1.11), aspiration pneumonitis; (OR 7.17; 95% CI 2.82-18.24), ICH volume > 30mls; OR 2.68; 95% CI 1.02-7.00)) low consumption of leafy vegetables (OR 0.36; 95% CI 0.15-0.85). CONCLUSION: This study identified risk and protective factors associated with 30-day mortality among West Africans with spontaneous ICH. These factors should be further investigated in other populations in Africa to enable the development of ICH mortality predictions models among indigenous Africans.

Dietary patterns associated with stroke among West Africans: A case-control study.

BACKGROUND: The relationship of diet with stroke risk among Africans is not well understood. AIM: The aim of this study was to investigate the association between dietary patterns and stroke risk among West Africans. METHODS: In this multi-center case-control study, 3684 stroke patients matched (for age and sex) with 3684 healthy controls were recruited from Nigeria and Ghana. Food consumption was assessed using a food frequency questionnaire, and dietary patterns were summarized using principal component analysis. Stroke was defined using predefined criteria primarily on clinical evaluation following standard guidelines. Conditional logistic regression was applied to compute odds ratio (OR) and 95% confidence interval (CI) for stroke risk by tertiles of dietary patterns adjusting for relevant confounders. RESULTS: Overall, mean age was 59.0 ± 13.9 years, and 3992 (54.2%) were males. Seven dietary patterns were identified. Multivariable-adjusted OR (95% CI) for risk of stroke by second and third tertiles (using the lowest and first tertile as reference) of dietary patterns was 1.65 (1.43, 1.90) and 1.74 (1.51, 2.02), for "poultry product and organ meat"; 1.69 (1.47, 1.96) and 1.51 (1.31, 1.75) for "red meat"; 1.07 (0.92, 1.23) and 1.21 (1.04, 1.40) for "fried foods and sweetened drinks"; 0.69 (0.60, 0.80) and 0.45 (0.39, 0.53) for "vegetables"; 0.84 (0.72, 0.97) and 0.81 (0.70, 0.93) for "whole-grain and fruit drinks"; and 0.97 (0.84, 1.12) and 0.85 (0.73, 0.98) for "fruits" respectively (p < 0.05). CONCLUSION: These data suggest that plant-based diets are associated with a lower risk of stroke and might be a beneficial dietary recommendation for the primary prevention of stroke among Africans.

MAPT allele and haplotype frequencies in Nigerian Africans: Population distribution and association with Parkinson's disease risk and age at onset.

INTRODUCTION: The association between MAPT and PD risk may be subject to ethnic variability even within populations of similar geographical origin. Data on MAPT haplotype frequencies, and its association with PD risk in black Africans are lacking. We aimed to determine the frequencies of MAPT haplotypes and their role as risk factors for PD and age at onset in Nigerians. METHODS: The haplotype and genotype frequencies of MAPT rs1052553 were analysed in 907 individuals with PD and 1022 age-matched healthy controls from the Nigeria Parkinson's Disease Research network cohort. Clinical data related to PD included age at study, age at onset (AAO), and disease duration. RESULTS: The frequency of the H1 haplotype was 98.7% in PD, and 99.1% in controls (p = 0.19). The H2 haplotype was present in - 1.3% of PD and 0.9% of controls (p = 0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and AAO (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p = 0.23). CONCLUSIONS: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans but document its occurrence in Nigerians. The MAPT H1 haplotype was not associated with an increased risk or age at onset of PD in this cohort.

MAPT allele and haplotype frequencies in Nigerian Africans: population distribution and association with Parkinson's disease risk and age at onset.

Background: The microtubule-associated protein tau ( MAPT ) gene is critical because of its putative role in the causal pathway of neurodegenerative diseases including Parkinson's disease (PD). However, there is a lack of clarity regarding the link between the main H1 haplotype and risk of PD. Inconsistencies in reported association may be driven by genetic variability in the populations studied to date. Data on MAPT haplotype frequencies in the general population and association studies exploring the role of MAPT haplotypes in conferring PD risk in black Africans are lacking. Objectives: To determine the frequencies of MAPT haplotypes and explore the role of the H1 haplotype as a risk factor for PD risk and age at onset in Nigerian Africans. Methods: The haplotype and genotype frequencies of MAPT rs1052553 were analysed using PCR-based KASP™ in 907 individuals with PD and 1,022 age-matched neurologically normal controls from the Nigeria Parkinson's Disease Research (NPDR) network cohort. Clinical data related to PD included age at study, age at onset, and disease duration. Results: The frequency of the main MAPT H1 haplotype in this cohort was 98.7% in individuals with PD, and 99.1% in healthy controls (p=0.19). The H2 haplotype was present in 41/1929 (2.1%) of the cohort (PD - 1.3%; Controls - 0.9%; p=0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and age at onset (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p=0.23). Conclusions: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans, but document its occurrence in the Nigerian population (2.1%). In this cohort of black Africans with PD, the MAPT H1 haplotype was not associated with an increased risk or age at onset of PD.

Determinants of First-Ever Stroke Severity in West Africans: Evidence From the SIREN Study.

Background Baseline stroke severity is probably partly responsible for poor stroke outcomes in sub-Saharan Africa. However, there is a paucity of information on determinants of stroke severity among indigenous Africans. We sought to identify the factors associated with stroke severity among West Africans in the SIREN (Stroke Investigative Research and Educational Networks) study. Methods and Results Stroke was diagnosed clinically and confirmed with brain neuroimaging. Severe stroke was defined as a Stroke Levity Scale score of ≤5. A multivariate logistic regression model was constructed to identify factors associated with stroke severity at 95% CI and a nominal cutoff of 5% type 1 error. A total of 3660 stroke cases were included. Overall, 50.7%% had severe stroke, including 47.6% of all ischemic strokes and 56.1% of intracerebral hemorrhage. Factors independently associated with severe stroke were meat consumption (adjusted odds ratio [aOR], 1.97 [95% CI, 1.43-2.73]), low vegetable consumption (aOR, 2.45 [95% CI, 1.93-3.12]), and lesion volume, with an aOR of 1.67 (95% CI, 1.03-2.72) for lesion volume of 10 to 30 cm3 and aOR of 3.88 (95% CI, 1.93-7.81) for lesion volume >30 cm3. Severe ischemic stroke was independently associated with total anterior circulation infarction (aOR, 3.1 [95% CI, 1.5-6.9]), posterior circulation infarction (aOR, 2.2 [95% CI, 1.1-4.2]), and partial anterior circulation infarction (aOR, 2.0 [95% CI, 1.2-3.3]) compared with lacunar stroke. Increasing age (aOR, 2.6 [95% CI, 1.3-5.2]) and lesion volume >30 cm3 (aOR, 6.2 [95% CI, 2.0-19.3]) were independently associated with severe intracerebral hemorrhage. Conclusions Severe stroke is common among indigenous West Africans, where modifiable dietary factors are independently associated with it. These factors could be targeted to reduce the burden of severe stroke.

Patient-level and system-level determinants of stroke fatality across 16 large hospitals in Ghana and Nigeria: a prospective cohort study.

BACKGROUND: Every minute, six indigenous Africans develop new strokes. Patient-level and system-level contributors to early stroke fatality in this region are yet to be delineated. We aimed to identify and quantify the contributions of patient-level and system-level determinants of inpatient stroke fatality across 16 hospitals in Ghana and Nigeria. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a multicentre study involving 16 sites in Ghana and Nigeria. Cases include adults (aged ≥18 years) with clinical and radiological evidence of an acute stroke. Data on stroke services and resources available at each study site were collected and analysed as system-level factors. A host of demographic and clinical variables of cases were analysed as patient-level factors. A mixed effect log-binomial model including both patient-level and system-level covariates was fitted. Results are presented as adjusted risk ratios (aRRs) with respective 95% CIs. FINDINGS: Overall, 814 (21·8%) of the 3739 patients admitted with stroke died as inpatients: 476 (18·1%) of 2635 with ischaemic stroke and 338 (30·6%) of 1104 with intracerebral haemorrhage. The variability in the odds of stroke fatality that could be attributed to the system-level factors across study sites assessed using model intracluster correlation coefficient was substantial at 7·3% (above a 5% threshold). Stroke units were available at only five of 16 centres. The aRRs of six patient-level factors associated with stroke fatality were: low vegetable consumption, 1·19 (95% CI 1·07-1·33); systolic blood pressure, 1·02 (1·01-1·04) for each 10 mm Hg rise; stroke lesion volume more than 30 cm3, 1·48 (1·22-1·79); National Institutes of Health Stroke Scale (NIHSS) score, 1·20 (1·13-1·26) for each 5-unit rise; elevated intracranial pressure, 1·75 (1·31-2·33); and aspiration pneumonia, 1·79 (1·16-2·77). INTERPRETATION: Studies are needed to assess the efficacy of interventions targeting patient-level factors such as aspiration pneumonia in reducing acute stroke fatality in this region. Policy directives to improve stroke unit access are warranted. FUNDING: US National Institutes of Health. TRANSLATIONS: For the Twi, Yoruba and Hausa translations of the abstract see Supplementary Materials section.

Frequency & factors associated with recurrent stroke in Ghana and Nigeria.

BACKGROUND: Data on the burden and outcomes of recurrent strokes in sub-Saharan Africa are limited, impeding efforts at optimal recurrent stroke prevention. OBJECTIVE: To assess the prevalence, risk factor profile, stroke types and mortality from recurrent strokes in Ghana and Nigeria. METHODS: We analyzed data from 3553 stroke cases involved in the Stroke Investigative Research and Educational Networks (SIREN) study for proportion with recurrent strokes. Conditional logistic regression models were constructed to interrogate for risk factors of recurrent stroke compared with stroke-free controls. Generalized Linear models were used to assess correlates of recurrent strokes relative to index strokes. RESULTS: Among stroke cases, 335 (9.4%) were recurrent strokes, of which 79.9% were ischemic and 20.1% hemorrhagic. Those with recurrent stroke were significantly older than index stroke cases 62.2 ± 12.9 years vs 58.9 ± 14.0 years, p < 0.01 respectively. Topmost risk factors associated with recurrent stroke were hypertension adjusted odds ratio 50.7 (95%CI: 6.6-392.7), dyslipidemia 2.8 (1.3-6.2), diabetes mellitus 4.0 (2.1-7.7) and family history of cardiovascular disease (CVD) 2.1 (1.1-4.2). The relative risk (95%CI) of factors associated with recurrent stroke vs index stroke were age > 50 years (1.5: 1.1-2.0); Hausa ethnicity (1.5:1.1-2.1), Yoruba ethnicity with Akan as referent; table added salt (0.4:0.2-0.8) and current alcohol intake (0.6:0.4-0.9). In-patient mortality among those with recurrent stroke vs. primary stroke was 20.5% vs. 21.4%. CONCLUSION: Several modifiable lifestyle related factors may warrant additional emphasis as targets for reducing the burden of recurrent stroke in sub-Saharan Africa.

Frequent vegetable consumption is inversely associated with hypertension among indigenous Africans.

AIMS: The relationship between vegetable consumption and hypertension occurrence remains poorly characterized in sub-Saharan Africa. This study assessed the association of vegetable consumption with odds of hypertension among indigenous Africans. METHODS AND RESULTS: We harmonized data on prior vegetable consumption and hypertension occurrence (defined as one of the following conditions; systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg or previous diagnosis or use of antihypertensive medications) from 16 445 participants across five African countries (Nigeria, South Africa, Kenya, Ghana and Burkina Faso) in the Stroke Investigative Research and Educational Network and Africa Wits-INDEPTH partnership for Genomic studies. Vegetable consumption (in servings/week) was classified as 'low' (<6). 'moderate' (6-11), 'sufficient' (12-29), and 'high' (≥30). Odds ratios (ORs) and 95% confidence interval (CI) of hypertension were estimated by categories of vegetable consumption (using 'low' consumption as reference), adjusting for sex, age in years, family history of cardiovascular diseases, education, smoking, alcohol use, physical inactivity, body mass index, diabetes mellitus and dyslipidaemia using logistic regressions at P < 0.05. The mean age of participants was 53.0 ( ± 10.7) years, and 7552 (45.9%) were males, whereas 7070 (42.9%) had hypertension. In addition, 6672(40.6%) participants had 'low' vegetable consumption, and 1758(10.7%) had 'high' vegetable consumption. Multivariable-adjusted OR for hypertension by distribution of vegetable consumption (using 'low' consumption as reference) were 1.03 (95% CI: 0.95, 1.12) for 'moderate' consumption; 0.80 (0.73, 0.88) for 'sufficient', and 0.81 (0.72, 0.92) for 'high' consumption, P-for-trend <0.0001. CONCLUSION: Indigenous Africans who consumed at least 12 servings of vegetables per week were less likely to be found hypertensive, particularly among males and young adults.