H3Africa AWI-Gen Collaborative Centre: a resource to study the interplay between genomic and environmental risk factors for cardiometabolic diseases in four sub-Saharan African countries.

Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40-60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.

Secondary preventive medication persistence and adherence 1 year after stroke.

OBJECTIVE: Data on long-term use of secondary prevention medications following stroke are limited. The Adherence eValuation After Ischemic stroke-Longitudinal (AVAIL) Registry assessed patient, provider, and system-level factors influencing continuation of prevention medications for 1 year following stroke hospitalization discharge. METHODS: Patients with ischemic stroke or TIA discharged from 106 hospitals participating in the American Heart Association Get With The Guidelines-Stroke program were surveyed to determine their use of warfarin, antiplatelet, antihypertensive, lipid-lowering, and diabetes medications from discharge to 12 months. Reasons for stopping medications were ascertained. Persistence was defined as continuation of all secondary preventive medications prescribed at hospital discharge, and adherence as continuation of prescribed medications except those stopped according to health care provider instructions. RESULTS: Of the 2,880 patients enrolled in AVAIL, 88.4% (2,457 patients) completed 1-year interviews. Of these, 65.9% were regimen persistent and 86.6% were regimen adherent. Independent predictors of 1-year medication persistence included fewer medications prescribed at discharge, having an adequate income, having an appointment with a primary care provider, and greater understanding of why medications were prescribed and their side effects. Independent predictors of adherence were similar to those for persistence. CONCLUSIONS: Although up to one-third of stroke patients discontinued one or more secondary prevention medications within 1 year of hospital discharge, self-discontinuation of these medications is uncommon. Several potentially modifiable patient, provider, and system-level factors associated with persistence and adherence may be targets for future interventions.

Motherhood, migration and mortality in Dikgale: modelling life events among women in a rural South African community.

OBJECTIVES: Although particular types of life events in populations are often studied separately, this study investigated the joint effects of three major event types in South African women's lives: motherhood, migration and mortality. STUDY DESIGN: Data were taken from a health and demographic surveillance site (HDSS) over an 11-year period, reflecting the entire population of a defined geographic area as an open cohort, in which individuals participated in regular longitudinal surveillance for health and demographic events. This HDSS is a member of the Indepth Network. METHODS: Multivariate Poisson regression models were built for each of the three life event types, in which individual person-time observed out of the total possible 11-year period was used as a rate multiplier. These models were used to calculate adjusted incidence rate ratios for each factor. RESULTS: In the 21,587 person-years observed for women aged 15-49 years, from 1996 to 2006, adjusted rate ratios for mortality and migration increased substantially over time, while motherhood remained fairly constant. Women who migrated were less likely to bear children; temporary migrants were at greater risk of dying, while permanent in-migrants had higher survival rates. Women who subsequently died were much less likely to bear children or migrate. CONCLUSIONS: The associations between motherhood, migration and mortality among these rural South African women were complex and dynamic. Extremely rapid increases in mortality over the period studied are presumed to reflect the effects of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. Understanding these complex interactions between various life events at population level is crucial for effective public health planning and service delivery.

Worse blood pressure control in patients with cerebrovascular or peripheral arterial disease compared with coronary artery disease.

OBJECTIVES: Poor blood pressure (BP) control is common amongst patients with symptomatic atherothrombotic disease. It is unclear whether BP control and management differ across atherothrombotic disease subtypes. METHODS: We analysed the baseline data of 44,984 patients with documented coronary artery disease (CAD) only (n = 30,414), cerebrovascular disease (CVD) only (n = 11,359) and peripheral arterial disease (PAD) only (n = 3211) from the international REduction of Atherothrombosis for Continued Health Registry and investigated the impact of atherothrombotic disease subtype on BP control and use of antihypertensive drugs. RESULTS: The proportion of patients with BP controlled (<140/90 mmHg) was higher in CAD (58.1%) than in CVD (44.8%) or PAD (38.9%) patients (P < 0.001). Amongst patients with treated hypertension, CAD patients were more likely to have BP controlled than were CVD patients [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 1.59-1.75] or PAD (OR = 2.30; 95% CI = 2.10-2.52). These differences were smaller in women than in men and decreased with age. Amongst treated patients, CAD patients were more likely to receive > or =3-drug combination therapies than were CVD (OR = 1.73; 95% CI = 1.64-1.83) or PAD (OR = 1.64; 95% CI = 1.49-1.80) patients. Adjustment for age, gender, waist obesity, diabetes, education level and world region did not alter the results. CONCLUSIONS: Coronary artery disease patients are more likely than CVD or PAD patients to have BP controlled and to receive antihypertensive drugs, particularly combination therapies. Promotion of more effective BP control through combination antihypertensive therapies could improve secondary prevention and therefore prevent complications in CVD and PAD patients.

High cardiovascular event rates in patients with asymptomatic carotid stenosis: the REACH Registry.

BACKGROUND AND PURPOSE: Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1-year outcomes of patients with ACAS > or =70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis. METHODS: The Reduction of Atherothrombosis for Continued Health Registry enrolled patients with either > or =3 atherothrombotic risk factors or established atherothrombotic disease. We investigated the 1-year follow-up data of patients for whom physicians reported presence/absence of ACAS at the time of inclusion. RESULTS: Compared with patients without ACAS (n = 30 329), patients with ACAS (n = 3164) had higher age- and sex-adjusted 1-year rates of transient ischaemic attack (3.51% vs. 1.61%, P < 0.0001), non-fatal stroke (2.65% vs. 1.75%, P = 0.0009), fatal stroke (0.49% vs. 0.26%, P = 0.04), cardiovascular death (2.29% vs. 1.52%, P = 0.002), the composite end-point cardiovascular death/myocardial infarction/stroke (6.03% vs. 4.29%, P < 0.0001) and bleeding events (1.41% vs. 0.81%, P = 0.002). In patients with ACAS, Cox regression analyses identified history of cerebrovascular ischaemic events as most important predictor of future stroke (HR 3.21, 95% CI 1.82-5.65, P < 0.0001). CONCLUSION: Asymptomatic carotid artery stenosis was associated with high 1-year rates of cardiovascular and cerebrovascular ischaemic events. Stroke was powerfully predicted by prior cerebrovascular ischaemic events.

Relationship between adiposity and pedometer-assessed ambulatory activity in adult, rural African women.

PURPOSE: To investigate the association between adiposity and pedometry-assessed ambulation in a convenience sample of adult, rural black South African women. METHODS: Pedometry data were collected over 7 days in 121 subjects. Adiposity measures included body mass index (BMI), waist circumference (WC) and percentage body fat (PBF). RESULTS: Sedentarism (<5000 steps day(-1)) was found in 13.7%, while 39.7% were classified as accruing sufficient physical activity (>or=10 000 steps day(-1)). Significant associations (P<0.02) existed between steps day(-1) and adiposity measures (r=-0.22 to -0.23). After adjusting for age, only BMI remained significantly associated with steps day(-1) (r=-0.20, P=0.032). Significant age-adjusted linear trends were found across combined BMI-WC risk categories for steps day(-1) (P=0.036). Adjusting for age, motor vehicle access, education, use of tobacco products and comorbidities, BMI decreased 1.4 kg m(-2) per 5000 steps day(-1) (P=0.035), access to a motor vehicle within the household increased PBF by 4% (P=0.018), and compared with sedentarism, the risk of obesity (BMI >or=30 kg m(-2)) was 52% lower at 10 000 steps day(-1) (P=0.028). CONCLUSION: Modest associations were found between adiposity and ambulation. Ambulation decreased the risk for obesity, while motor vehicle access was associated with increased adiposity levels.

Diagnosing temporal arteritis: duplex vs. biopsy.

BACKGROUND: Temporal artery biopsy is the traditionally-accepted method of diagnosing temporal arteritis, but is of limited sensitivity. AIM: To compare the clinical decisions made after negative temporal artery biopsy vs. negative temporal artery duplex, and the effects on patient outcomes. DESIGN: Retrospective analysis. METHODS: Of 290 patients suspected of having temporal arteritis, 147 underwent bilateral temporal artery duplex with a negative result, and 143 underwent unilateral temporal artery biopsy with a negative result. These groups were compared. Dependent measures included the proportion of patients in each group whose steroids were discontinued by their primary care doctor after either negative test, and the difference in the number of alternative diagnoses considered after a negative test. The incidence of blindness in each group was also compared, as a measure of adverse outcomes. Patients were then stratified by pre-test probability of having the disease, and compared using the same measures. RESULTS: Equivalent proportions of patients in the two groups had steroids discontinued after a negative test result, even when further stratified into risk groups by the probability of having temporal arteritis. No differences in adverse outcomes or number of alternative diagnoses considered were noted between groups. DISCUSSION: In clinical practice, bilateral temporal artery duplex served the same function as biopsy, but without subjecting patients to the potential morbidity of a surgical procedure. Temporal artery biopsy could be reserved only for situations where the duplex result is inconsistent with the clinical picture, and the biopsy result, if different from the duplex result, might influence the treatment decision.

Current strategies for ischemic stroke prevention: role of multimodal combination therapies.

Stroke remains a global leading cause of death and long-term disability, highlighting the need for more effective treatment approaches. The majority of strokes are of ischemic origin, often caused by large- or small-artery atherothrombosis, or cardioembolism. Considering the systemic nature of the atherothrombotic disease process, stroke patients are at increased risk for ischemic events in several vascular territories: cerebral, coronary and peripheral. Due to the limited options for acute stroke therapies, stroke prevention is an important therapeutic approach. In addition to the management of modifiable risk factors such as hypertension, dyslipidemia and smoking through pharmacotherapy or lifestyle adjustments, anticoagulants, surgical and perhaps endovascular approaches are indicated in certain patients. Antiplatelet therapies using various agents are a cornerstone of secondary stroke prevention. To ensure the appropriate continuum of care after hospitalization for ischemic stroke, some interventions for the prevention of recurrent ischemic stroke should be initiated during the acute hospitalization setting and maintained in the out-patient setting.

Association between insulin-like growth factor-1, insulin-like growth factor-binding protein-1 and leptin levels with nutritional status in 1-3-year-old children, residing in the central region of Limpopo Province, South Africa.

The present study evaluated levels of growth factors and their associations with nutritional status with emphasis on stunting in children at 1 and 3 years of age. A follow-up study on a birth cohort (n 219) of children from villages in the central region of the Limpopo Province was undertaken. Of the original cohort, 156 and 162 could be traced and assessed at ages 1 and 3 years, respectively. Data collected included socio-demographic characteristics, anthropometric measurements, dietary intake and fasting blood (collected from 116 and 145 children at 1 and 3 years, respectively) for growth factor analysis (insulin-like growth factor (IGF)-1, IGF binding protein (BP)-1, IGFBP-3, leptin, glucose and insulin). At 1 year it was found that stunted children had lower leptin levels while their IGFBP-1 levels were higher than that in normal children. These differences were, however, not observed at 3 years. Furthermore at 1 year the biochemical parameters were more related to length measures whereas at 3 years the parameters were more associated with weight measures. The observed stunting in this group of children may be a result of chronic undernutrition resulting in long-term growth faltering which is already evident at 1 year. Thus the observed phenomenon might be an adaptive mechanism adopted by children's metabolic processes as they grow up in an environment with inadequate essential nutrients due to poor weaning practices and consumption of a diet of poor quality, resulting in them gaining more weight at the expense of linear growth.

Prevalence of gestational diabetes mellitus and the effect of weight on measures of insulin secretion and insulin resistance in third-trimester pregnant rural women residing in the Central Region of Limpopo Province, South Africa.

AIMS: To examine the prevalence of gestational diabetes in third-trimester pregnant women as well as to assess their insulin secretion and insulin resistance (IR). METHODS: Third-trimester pregnant women (n= 262) attending antenatal care at local clinics in the central region of the Limpopo Province underwent a 2-h oral glucose tolerance test (OGTT) with blood collected at 0, 30 and 120 min. Glucose and insulin were measured. RESULTS: The prevalence of gestational impaired glucose tolerance (GIGT) and gestational diabetes mellitus (GDM) was 8.8% (7.3% GIGT; 1.5% GDM). Women with GIGT/GDM were significantly older and had more children compared with women with a normal response to the OGTT. Homeostasis model assessment(HOMA)-IR and fasting insulin were lower in the GIGT/GDM group compared with the normal group, as were measures of insulin secretion (HOMA B-cell function and insulinogenic index). Furthermore, women with body mass index (BMI)> or =30.0 kg/m2 were significantly older and had higher parity, systolic and diastolic blood pressure measurements than those with BMI 25.0-29.9 kg/m2 and BMI < 25.0 kg/m2. However,increased BMI was not associated with an increased risk of GIGT/GDM. CONCLUSION: The present study shows that there is a high prevalence of GIGT/GDM, with most women having IGT. The GIGT/GDM present in these women is characterized by increased insulin sensitivity accompanied by reduced pancreatic B-cell function. Additionally, heavier women appear to have increased first phase insulin secretion, suggesting the presence of insulin resistance.

Effect of Traditional Beer Consumption on the Iron Status of A Rural South African Population

Objective.To determine the effect of traditional beer consumption on the iron status of rural black subjects.Design. A cross-sectional study was undertaken.Setting. Dikgale field site and the surrounding villages in Limpopo Province; South Africa.Subjects. Eight hundred and forty-four non-alcohol consumers (738 women and 106 men) and 280 alcohol consumers (163 women and 117 men) aged 30 years and above; participated in the study.Outcome measures. Outcome measures included alcohol consumption; serum ferritin levels; percentagetransferrin saturation; total iron-binding capacity; haemoglobin and C-reactive protein levels.Results. Traditional beer fermented in either iron pots or plastic containers was found to have iron levels ranging from 15 mg/l to 67.8 mg/l and 6 mg/l to 17 mg/l; respectively. Iron status as measured by serum ferritin; serum iron; percentage transferrin saturation; and haemoglobin levels was significantly higher in alcohol consumers than in non-consumers; even after adjustment for age and C-reactive protein (CRP) levels. A high percentage of women (12.3) and men (8.2) consuming alcohol had iron overload.Conclusion. This study showed that consumption of traditional beer in a non-urban population in Limpopo Province was associated with high levels of markers of iron status. Traditional beer consumption seemed to prevent iron deficiency in those at risk of developing such deficiency; but appeared to precipitate iron overload in those at risk of developing iron overload

Acute physiological derangement is associated with early radiographic cerebral infarction after subarachnoid haemorrhage.

BACKGROUND: Cerebral infarction after aneurysmal subarachnoid haemorrhage (SAH) is presumed to be due to cerebral vasospasm, defined as arterial lumen narrowing from days 3 to 14. METHODS: We reviewed the computed tomography scans of 103 patients with aneurysmal SAH for radiographic cerebral infarction and controlled for other predictors of outcome. A blinded neuroradiologist reviewed the angiograms. Cerebral infarction from vasospasm was judged to be unlikely if it was visible on computed tomography within 2 calendar days of SAH or if angiography showed no vasospasm in a referable vessel, or both. RESULTS: Cerebral infarction occurred in 29 (28%) of 103 patients with SAH. 18 patients had cerebral infarction that was unlikely to be due to vasospasm because it was visible on computed tomography by day 2 (6 (33%)) or because angiography showed no vasospasm in a referable artery (7 (39%)), or both (5 (28%)). In a multivariate model, cerebral infarction was significantly related to World Federation of Neurologic Surgeons grade (odds ratio (OR) 1.5/grade, 95% confidence interval (CI) 1.1 to 2.01, p = 0.006) and SAH-Physiologic Derangement Score (PDS) >2 (OR 3.7, 95% CI 1.4 to 9.8, p = 0.01) on admission. Global cerebral oedema (OR 4.3, 95% CI 1.5 to 12.5, p = 0.007) predicted cerebral infarction. Patients with cerebral infarction detectable by day 2 had a higher SAH-PDS than patients with later cerebral infarction (p = 0.025). CONCLUSIONS: Many cerebral infarctions after SAH are unlikely to be caused by vasospasm because they occur too soon after SAH or because angiography shows no vasospasm in a referable artery, or both. Physiological derangement and cerebral oedema may be worthwhile targets for intervention to decrease the occurrence and clinical impact of cerebral infarction after SAH.

Location characteristics of early perihaematomal oedema.

BACKGROUND: The natural history and triggers of perihaematomal oedema (PHO) remain poorly understood. Cerebral amyloid angiopathy (a common cause of lobar haemorrhage) has localised anticoagulant and thrombolytic properties, which may influence PHO. We hypothesised that early (within 24 hours) oedema to haematoma volume ratios are smaller in patients with lobar intracerebral haemorrhage (ICH) than in patients with deep ICH. METHODS: Haematoma and PHO volumes were measured in consecutive patients admitted to an acute stroke unit with a diagnosis of spontaneous supratentorial ICH proven by computed tomography. The oedema to haematoma volume ratios were calculated and compared in patients with lobar ICH and deep ICH. RESULTS: In total, 44 patients with ICH were studied: 19 patients had deep ICH, median haematoma volume 8.4 ml (interquartile range (IQR) 4.8 to 20.8), median PHO 8.2 ml (2.8 to 16), and 25 had lobar ICHs, median haematoma volume 17.6 ml (6.6 to 33.1) and median oedema volume 10.2 ml (3.4 to 24.2). Patients with lobar ICH were older than those with deep ICH (65.7 v 57.4 years, p = 0.009) but ICH location did not differ by sex or race. There was no evidence that haematoma or oedema volumes were related to type of ICH (p = 0.23, p = 0.39 respectively). The median oedema to haematoma volume ratios were similar in patients with lobar and deep ICH (0.67 v 0.58, p = 0.71). Controlling for age, sex, and race made little difference to these comparisons. CONCLUSIONS: There are no major location specific differences in PHO volumes within 24 hours of ICH onset. Deep and lobar ICH may have common therapeutic targets to reduce early PHO.

A systematic review of Terson's syndrome: frequency and prognosis after subarachnoid haemorrhage.

OBJECTIVE: To review systematically the frequency and prognostic significance of vitreous haemorrhage in patients with subarachnoid haemorrhage (Terson's syndrome). METHODS: Papers relating to vitreous haemorrhage in patients with subarachnoid haemorrhage were retrieved. The only studies considered were those with at least 10 consecutive cases of subarachnoid haemorrhage with or without vitreous haemorrhage. The frequency of vitreous haemorrhage in such cases was calculated in prospective and retrospective studies. Mortality was compared in patients with and without Terson's syndrome. RESULTS: 154 papers were reviewed. Three prospective studies and six retrospective studies satisfied the inclusion criteria. Of 181 patients with subarachnoid haemorrhage assessed prospectively (mean age, 51.7 years), 24 (13%) had vitreous haemorrhage; among 1086 retrospective records, 37 (3%) had documented vitreous haemorrhage (p<0.001). Patients with Terson's syndrome had higher Hunt and Hess grades than those without (mean grade, 3.6 v 2.6). Patients with Terson's syndrome were also more likely to die (13 of 30 (43%) v 31 of 342 (9%); odds ratio 4.8; p<0.001). CONCLUSIONS: Prospective studies show a higher frequency of Terson's syndrome than retrospective studies, suggesting that vitreous haemorrhage is not well documented. Vitreous haemorrhage is an adverse prognostic finding in patients with subarachnoid haemorrhage.

The effect of different apo(a) isoforms on plasminogen activation in black South African subjects.

OBJECTIVE: The present study evaluates the effect of different apolipoprotein(a) [apo(a)] isofroms on plasminogen activation. DESIGN: A cross-sectional study. SETTING: A rural village (Dikgale district) in the Northen Province of South Africa. SUBJECT: A total of 90 apparently healthy subjects (64 females and 36 males) aged 43 to 67 years participated in the study. RESULTS: The mean lipoprotein(a) [ Lp(a)] level in the subjects was 38.14 +/- 22.34 mg/dl. No association was found between Lp(a) isoforms. When the ratio of Lp(a):plasminogen was less then 1.3, a competitive inhibition was observed, but when the ratio exceeded 1.3, an uncompetitive inhibition was observed with all isoforms. CONCLUSION: The results of the present study suggest that the inhibition of plasminogen activation by Lp(a) is not dependent of apo(a) size.

Establishment of primary stroke centers: a survey of physician attitudes and hospital resources.

OBJECTIVES: To survey US physicians involved in acute stroke care to determine the proportion of hospitals that currently meet the recommended Brain Attack Coalition (BAC) criteria for Primary Stroke Centers (PSC) and obtain opinions regarding the value of stroke centers. METHODS: A survey regarding the BAC guidelines for the establishment of stroke centers was mailed to 3,245 US neurologists, neurosurgeons, and emergency physicians. RESULTS: A total of 1,032 responses were received. Seventy-nine percent (range by specialty 58 to 98%) of respondents believed there was a need for stroke centers. If formal stroke center designation were established, 81% (range 72 to 90%) would like their hospital to become a PSC. Although 77% of respondents believed that their hospital currently met recommended criteria for a PSC, only 7% actually meet all recommended elements. However, 44% of hospitals already provide most acute stroke services. The BAC criteria most frequently lacking were continuing medical education for professional stroke center staff, stroke training for emergency department staff, formal establishment of a stroke unit, and designation of a stroke center director. CONCLUSIONS: The majority of emergency medicine and neuroscience physician respondents involved in acute stroke care support the designation of primary stroke centers. Although respondents globally overestimated the extent to which their facilities currently meet BAC recommended criteria for PSC, detailed responses suggested that over 40% of hospitals possess substantial existing acute stroke care resources and are poised to function as PSC with modest additional administrative and financial commitment.

Effect of apolipoprotein E genotype on in-hospital mortality following intracerebral haemorrhage.

OBJECTIVE: To determine the relationship between the apolipoprotein E (APOE) epsilon4 allele and in-hospital mortality from intracerebral haemorrhage (ICH). MATERIAL AND METHODS: Patients admitted to two acute stroke units with ICH were prospectively evaluated and APOE genotyped. In-hospital survival was recorded in 176 patients. RESULTS: There were 85 men and 91 women, mean age 68 years. Fifty-two (30%) of the 176 patients died in hospital. After adjusting for sex, age, hospital, and race, increased age (P = 0.009) and the presence of the APOEepsilon4 allele (P = 0.026) significantly reduced in-hospital survival. CONCLUSION: The APOEepsilon4 allele in this population may be associated with poor survival following ICH.

Familial clustering of intracerebral hemorrhage: a prospective study in North Carolina.

Few studies have assessed the frequency of familial clustering in intracerebral hemorrhage (ICH). Of 144 patients with ICH prospectively assessed, 14 (9.8%) had a positive family history of ICH (FH+). Four pedigrees had more than two affected family members. Comparisons between FH+ and FH- probands demonstrated no significant differences in race, age, sex, ICH type or location. An underlying genetic etiology may account for familial clustering in some ICH patients.