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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Secondhand smoke exposure is independently associated with stroke among non-smoking adults in West Africa.

BACKGROUND: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans. OBJECTIVE: To evaluate the association of SHSE with stroke among indigenous Africans. METHODS: We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05. RESULTS: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes. CONCLUSION: Culturally relevant primary prevention strategies targeted at SHSE might be promising in preventing stroke among Africans.

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.

The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13-3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19-0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD.

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.

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.

Determinants of metabolic syndrome and its prognostic implications among stroke patients in Africa: Findings from the Stroke Investigative Research and Educational Network (SIREN) study.

BACKGROUND: The prognostic implications of metabolic syndrome (METS) among African stroke patients are poorly understood. This study aimed to investigate the determinants of METS and its prognostic implications among Africans with newly diagnosed stroke in the SIREN study. METHODS: We included stroke cases (adults aged >18 years with CT/MRI confirmed stroke). The validated tools comprehensively evaluated vascular, lifestyle, and psychosocial factors. We used logistic regression to estimate adjusted odds ratios (OR) with 95% CIs for the association between METS and risk factors. We also computed the prediction power of the domain of covariates in a sequential manner using the area under the receiver operating curve (ROC) curve. RESULTS: Among 3998 stroke subjects enrolled in the study, 76.8% had METS by at least one of the clinical definitions. Factors associated with METS were age > 50 years (OR- 1.46, CI-1.19-1.80), male gender (OR 4.06, CI- 3.28-5.03), income >100USD (OR1.42, CI-1.17-1.71), stress (OR1.46, CI-1.14-1.87), family history of diabetes mellitus (OR1.38, CI-1.06-1.78), and cardiac disease (OR1.42, CI-1.18-1.65). Stroke severity was higher among those with METS (SLS = 5.8 ± 4.3) compared with those without METS (6.2 ± 4.5) at p = 0.037. METS was associated with higher odds (aOR 1.31, CI-1.08-1.58) of one-month fatality after adjusting for stroke severity, age > 50 years, and average monthly income >100USD. CONCLUSION: METS is very common among African stroke patients and is associated with stroke severity and worse one-month fatality. Lifestyle interventions may prevent METS and attenuate its impact on stroke occurrence and outcomes.

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.

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.

Carotid and Vertebral Atherosclerosis in West African Stroke Patients: Findings from the Stroke Investigative Research and Education Network.

Background: We evaluated the characteristics of carotid and vertebral atherosclerosis in indigenous West Africans with stroke. Methodology: Of the 3778stroke patients recruited between 01/2014 and 08/2017, 1070 (28.3%) received carotid and vertebral artery evaluation with B-mode Ultrasound. Carotid and vertebral intima-media thickness (IMT) using multiple site technique were measured bilaterally and plaque frequency was determined. Descriptive and comparative analyses between stroke types and vessels were carried out. Results: There were 809 (75.6%) patients with ischemic stroke. The prevalence of intima-media thickening in the study population was 84.0% (898/1070) [95% CI: 81.7-86.1], being higher in the ischemic stroke (688/809, 85.0%) [95% CI: 82.4-87.3] than in the hemorrhagic stroke group (211/261, 80.8%) [95% CI: 75.6-85.2]. Overall prevalence of plaques which was 26.1% [95% CI: 23.5-28.8], was found also to be higher in ischemic than hemorrhagic stroke (29.8%[95% CI: 26.7-33.0] vs. 14.6% [95% CI: 10.8-19.4], p < 0.05). The mean IMT (carotids: 2.01+1.33 mm; vertebrals: 0.96+0.54mm, p<0.001) and prevalence of plaques (carotids: 8.8%; vertebrals: 1.7%,p<0.001) were higher in carotid than vertebral arteries. Age, hypertension, level of formal education, history of smoking, average monthly income, and family histories of hypertension and stroke were associated with intima-media thickening in the carotids (all p< 0.05) in the ischemic stroke patients while family history of hypertension, diabetes mellitus, and level of formal education were independently associated with intima-media thickening in the carotids (all p< 0.05) in the hemorrhagic stroke patients. No CVRF showed an independent association with the presence of plaque in the carotid and vertebral arteries both stroke types. Conclusions: One off our stroke patients in our cohort had atherosclerotic plaques, with ischemic patients being twice as likely to have this burden compared to hemorrhagic patients, and carotid atherosclerosis being five times as frequent as vertebral atherosclerosis.