FACULTY OF PUBLIC HEALTH
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Item Differential impact of risk factors on stroke occurrence among men versus women in West Africa The SIREN Study(American Heart Association, Inc., 2019) Akpalu A.; Gebregziabher M.; Ovbiagele B.; Sarfo F.; Iheonye H.; Akinyemi R.; Akpa O.; Tiwari H. K.; Arnett D.; Wahab K.; Lackland D.; Abiodun A.; Ogbole G.; Jenkins C.; Arulogun O.; Akpalu J.; Obiako R.; Olowoyo P.; Fawale M.; Komolafe M.; Osaigbovo G.; Obiabo Y.; Chukwuonye I.; Owolabi L.; Adebayo P.; Sunmonu T.; Owolabi M.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.Item Echocardiographic abnormalities and determinants of 1-month outcome of stroke among West Africans in the SIREN Study(American Heart Association, 2019) Adeoye A. M.; Ovbiagele B.; Akinyemi J. O.; Ogah O. S.; Akinyemi R.; Gebregziabher M.; Wahab K.; Fakunle A. G.; Akintunde A.; Adebayo O.; Aje A.; Tiwari H. K; Arnett D.; Agyekum F.; Appiah L. T.; Amusa G.; Olunuga T. O.; Akpa O.; Sarfo F. S.; Akpalu A.; Jenkins C.; Lackland D.Background-—Little is known about the relationship between echocardiographic abnormalities and outcome among patients with acute stroke. We investigated the pattern and association of baseline echocardiographic variables with 1-month disability and mortality among patients with stroke in the SIREN (Stroke Investigative Research and Education Network) study. Methods and Results-—We enrolled and followed up consecutive 1020 adult patients with acute stroke with baseline transthoracic echocardiography from west Africa. To explore the relationship between echocardiographic variables and 1-month disability (using modified Rankin scale >3) and fatality, regression models were fitted. Relative risks were computed with 95% CIs. The participants comprised 60% men with a mean age of 59.2_14.6 years. Ischemic stroke was associated with smaller aortic root diameter (30.2 versus 32.5, P=0.018) and septal (16.8 versus 19.1, P<0.001) and posterior wall thickness at systole (18.9 versus 21.5, P=0.004). Over 90% of patients with stroke had abnormal left ventricular (LV) geometry with eccentric hypertrophy predominating (56.1%). Of 13 candidate variables investigated, only baseline abnormal LV geometry (concentric hypertrophy) was weakly associated with 1-month disability (unadjusted relative risk, 1.80; 95% CI, 0.97–5.73). Severe LV systolic dysfunction was significantly associated with increased 1-month mortality (unadjusted relative risk, 3.05; 95% CI, 1.36–6.83). Conclusions-—Nine of 10 patients with acute stroke had abnormal LV geometry and a third had systolic dysfunction. Severe LV systolic dysfunction was significantly associated with 1 month mortality. Larger studies are required to establish the independent effect and unravel predictive accuracy of this associationItem Knowledge, attitudes and practices of West Africans on genetic studies of stroke: Evidence from the SIREN Study(World Stroke Organization Reprints and permissions, 2018) Akinyemi R. O.; Sarfo F. S.; Akinyemi J.; Singh A.; Akpa M. O.; Akpalu A.; Owolabi L.; Adeoye A. M.; Obiako R.; Wahab K.; Sanya E.; Komolafe M.; Ogbole G.; Fawale M.; Adebayo P.; Osaigbovo G.; Sunmonu T.; Olowoyo P.; Chukwuonye I.; Obiabo Y.; Adeniji O.; Fakunle G.; Melikam E.; Saulson R.; Yaria J.; Uwanruochi K.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 (OR¼0.82, CI: 0.72–0.94), being currently unmarried (OR ¼ 0.81, CI: 0.70–0.92), and alcohol use (OR ¼ 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 ¼ 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 interventionsItem Stroke Among Young West Africans Evidence From the SIREN (Stroke Investigative Research and Educational Network) Large Multisite Case–Control Study.(American Heart Association, Inc., 2019) Sarfo F. S.; Ovbiagele B.; Gebregziabher M.; Wahab K.; Akinyemi R. O.; Akpalu A.; Akpa O.; Obiako R.; Owolabi L.; Jenkins C.; Owolabi M. O.Background and purpose: Stroke in lower and middle-income countries affects a young and productive age group. Data on factors associated with stroke in the young are sorely lacking from lower and middle-income countries. Our objective is to characterize the nature of stroke and its risk factors among young West Africans aged <50 years old. Methods: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Nigeria and Ghana. Cases included adults aged ≥18 years with computed tomography/magnetic resonance imaging-confirmed stroke. Controls were age-and gender-matched stroke-free adults recruited from the communities in catchment areas of cases. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed. We used conditional logistic regression to estimate odds ratios and population attributable risks with 95% confidence intervals. Results: Five hundred fifteen (24.3%) out of 2118 cases enrolled were <50 years old. Among subjects <50 years old, hemorrhagic stroke proportion was 270 (52.5%) versus 245 (47.5%) for ischemic strokes. Etiologic subtypes of ischemic strokes included large artery atherosclerosis (40.0%), small vessel disease (28.6%), cardioembolism (11.0%), and undetermined (20.4%). Hypertension (91.7%), structural lesions (3.4%), and others (4.9%) were causally associated with hemorrhagic stroke. Six topmost modifiable factors associated with stroke in descending order of population attributable risk (95% confidence interval) were hypertension: 88.7% (82.5%-94.8%), dyslipidemia: 48.2% (30.6%-65.9%), diabetes mellitus: 22.6% (18.7%-26.5%), low green vegetable consumption: 18.2% (-6.8%-43.2%), stress: 14.5% (4.9%-24.1%), and cardiac disease: 8.4% (5.8%-11.1%). Conclusions: The high and rising burden of stroke among young Africans should be curtailed via aggressive, population-wide vascular risk factor control.Item Dominant modifiable risk factors for stroke in Ghana and and Nigeria (SIREN): a case-control study(Elsevier Ltd., 2018) Owolabi M. O.; Sarfo F. S.; Akinyemi R. O.; Gebregziabher M.; Akpa O.; Akpalu A.; Wahab K.; Obiako R.; Owolabi L.; Ovbiagele B.Background Sub-Saharan Africa has the highest incidence, prevalence, and fatality from stroke globally. Yet, only little information about context-specific risk factors for prioritising interventions to reduce the stroke burden in sub-Saharan Africa is available. We aimed to identify and characterise the effect of the top modifiable risk factors for stroke in sub Saharan Africa. Methods The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study done at 15 sites in Nigeria and Ghana. Cases were adults (aged ≥18 years) with stroke confirmed by CT or MRI. Controls were age-matched and gender-matched stroke-free adults (aged ≥18 years) recruited from the communities in catchment areas of cases. Comprehensive assessment for vascular, lifestyle, and psychosocial factors was done using standard instruments. We used conditional logistic regression to estimate odds ratios (ORs) and population attributable risks (PARs) with 95% CIs. Findings Between Aug 28, 2014, and June 15, 2017, we enrolled 2118 case-control pairs (1192 [56%] men) with mean ages of 59•0 years (SD 13•8) for cases and 57•8 years (13•7) for controls. 1430 (68%) had ischaemic stoke, 682 (32%) had haemorrhagic stroke, and six x (<1%) had discrete ischaemic and haemorrhagic lesions. 98•2% (95% CI 97•2–99•0) of adjusted PAR of stroke was associated with 11 potentially modifiable risk factors with ORs and PARs in descending order of PAR of 19•36 (95% CI 12•11–30•93) and 90•8% (95% CI 87•9–93•7) for hypertension, 1•85 (1•44–2•38) and 35•8% (25•3–46•2) for dyslipidaemia, 1•59 (1•19–2•13) and 31•1% (13•3–48•9) for regular meat consumption, 1•48 (1•13–1•94) and 26•5% (12•9–40•2) for elevated waist-to-hip ratio, 2•58 (1•98–3•37) and 22•1% (17•8–26•4) for diabetes, 2•43 (1•81–3•26) and 18•2% (14•1–22•3) for low green leafy vegetable consumption, 1•89 (1•40–2•54) and 11•6% (6•6–16•7) for stress, 2•14 (1•34–3•43) and 5•3% (3•3–7•3) for added salt at the table, 1•65 (1•09–2•49) and 4•3% (0•6–7•9) for cardiac disease, 2•13 (1•12–4•05) and 2•4% (0•7–4•1) for physical inactivity, and 4•42 (1•75–11•16) and 2•3% (1•5–3•1) for current cigarette smoking. Ten of these factors were associated with ischaemic stroke and six with haemorrhagic stroke occurrence. Interpretation Implementation of interventions targeting these leading risk factors at the population level should substantially curtail the burden of stroke among Africans.Item Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke(Elsevier Inc., 2017) Owolabi M.; Ogbole G.; Akinyemi R.; Salaam K.; Akpa O.; Mongkolwat P.; Omisore A.; Agunloye A.; Efidi R.; Odo J.; Makanjuola A.; Akpalu A.; Sarfo F.; Owolabi L.; Obiako R.; Wahab K.; Sanya E.; Adebayo P.; Komolafe M.; Adeoye A. M.; Fawale M. B."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 con cordant and reproducible classification of stroke subtypes by multiple investigators, making it suitable for clinical use and multicenter research.Item African Ancestry, APOL1, candidate genes, CDKN2A/CDKN2B, HDAC9, small vessel disease, stroke, West Africa(John Wiley & Sons Ltd, 2017) Akinyemi R.; Tiwari H. K.; Arnett D. K.; Ovbiagele B.; Irvin M. R.; Wahab K.; Sarfo F.; Srinivasasainagendra V.; Adeoye A.; Perry R. T.; Akpalu A.; Jenkins C.; Arulogun O.; Gebregziabher M.; Owolabi L.; Obiako R.; Sanya E.; Komolafe M.; Fawale M.; Adebayo P.; Osaigbovo G.; Sunmonu T.; Olowoyo P.; Chukwuonye I.; Obiabo Y.; Onoja A.; Akinyemi J.; Ogbole G.; Melikam S.; Saulson R.; Owolabi M.Objective: Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) is chemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Materials and Methods: Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging—confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls. Results: Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P value = .013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P – value = .026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value = .014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value = .036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations. Conclusion: This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from AfricaItem Interleukin–6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men(Elvsevier B. V, 2017) Akinyemi R.; Arnett D. K.; Tiwari H. K.; Ovbiagele B.; Sarfo F.; Srinivasasainagendra V.; Irvin M. R.; Adeoye A.; Perry R. T.; Akpalu A.; Jenkins C.; Owolabi L.; Obiako R.; Wahab K.; Sanya E.; Komolafe M.; Fawale M.; Adebayo P.; Osaigbovo G.; Sunmonu T.; Olowoyo P.; Chukwuonye I.; Obiabo Y.; Akpa O.; Melikam S.; Saulson R.; Kalaria R.; Ogunniyi A.; Owolabi M.Background: Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub - Saharan African populations. Interleukin–6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. Aim: Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6, CDKN2A CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Methods: Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardio vascular disease risk factors were constructed to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 429) of ischemic stroke (Men = 198; Women = 231) and stroke– free (N = 483) controls (Men = 236; Women = 247). Results: Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans = 8.6%) was significantly associated with ischemic stroke in men (OR = 2.006, 95% CI = [1.065, 3.777], p = 0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans = 1.7%) was also associated with ischemic stroke in men (OR = 2.550, 95% CI = [1.027, 6.331], p = 0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke.Item Prevalence and prognostic features of ECG abnormalities in acute stroke(Elsevier Ltd, 2017) Adeoye A. M.; Ogah O. S.; Ovbiagele B.; Akinyemi R.; Shidali V.; Agyekum F.; Aje A.; Adebayo O.; Akinyemi J. O.; Kolo P.; Appiah L. T.; Iheonye H.; Kelechukwu U.; Ganiyu A.; Olunuga T. O.; Akpa O.; Olagoke O. O.; Sarfo F. S.; Wahab K.; Olowookere S.; Fakunle A.; Akpalu A.; Adebayo P. B.; Nkromah K.; Yaria J.; Ibinaiye P.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 out comes 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 ¼ 0.002), but more likely to have left ventricular hypertrophy (64.4% vs. 51.4%; p ¼ 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 disabilityItem Exploring overlaps between the genomic and environmental determinants of LVH and stroke(Elsevier Ltd, 2017) Adeoye A. M.; Ovbiagele B.; Kolo P.; Appiah L.; Ajek A.; Adebayo O.; Sarfo F.; Akinyemi J.; Adekunle G.; Agyekum F.; Shidali V.; Ogah O.; Lackland D.; Gebregziabher M.; Arnett D.; Tiwari H. K.; Akinyemi R.; Olagoke O. O.; Oguntade A. S.; Olunuga T.; Uwanruochi K.; Jenkins C.; Adadey P.; Iheonye H.; Owolabi L.; Obiako R.; Akinjopo S.; Armstrong K.; Akpalu A.; Fakunle A.; Saulson R.; Aridegbe M.; Olowoyo P.; Osaigbovo G.; Akpa O.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 ¼ 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 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