Blood Pressure Indices and Associated Risk Factors in a Rural West African Adult Population: Insights from an AWI-Gen Substudy in Ghana.

Systolic (SBP) and diastolic blood pressure (DBP) are commonly used for cardiovascular disease (CVD) risk prediction, and pulse pressure (PP) and mean arterial blood pressure (MAP) can provide additional information. It is therefore important to understand the factors associated with these cardiovascular risk markers. This cross-sectional study involved 1839 men and women aged 40-60 years. Data on SBP, DBP, MAP, PP, sociodemography, lifestyle, anthropometry, and lipids were collected. Gender-stratified linear regression analyses were performed to determine the association between log-transformed blood pressure indices and the study variables. Age was associated with all measured blood pressure indices (p < 0.001) among men and women. Men had higher SBP (p=0.007) and PP (p < 0.001) than women. Nankana ethnicity was associated with higher PP levels (p < 0.005) in the total population. Vendor meal consumption among women was associated with higher PP levels (p < 0.05). Fruit intake among men was associated with lower PP levels (p < 0.05). Currently unmarried women had higher SBP (p < 0.005), DBP (p < 0.05), MAP (p < 0.005), and PP (p < 0.005) than currently married women. Pesticide exposure was negatively associated with SBP (p < 0.005), DBP (p < 0.005), MAP (p < 0.005), and PP (p < 0.05) among women. Increased subcutaneous fat was associated with DBP (p < 0.005) and MAP (p < 0.05) among women. Among men, hip circumference was associated with higher DBP and MAP (p < 0.05 for both associations), subcutaneous fat associated with higher SBP (p < 0.005), DBP (p < 0.001), and MAP (p < 0.001) and visceral fat was associated with higher PP (p < 0.05). In the total population, visceral fat was associated with higher DBP (p < 0.05) and MAP (p < 0.001). High-density lipoprotein cholesterol was positively associated with SBP (p < 0.005), DBP (p < 0.005), and MAP (p < 0.001) for women and positively associated with SBP, DBP, and MAP (p < 0.001 for all three) and PP (p < 0.05) for men. The association of blood pressure indices with modifiable risk factors suggests that targeted health interventions may reduce CVD risk in this population.

Regional Patterns and Association Between Obesity and Hypertension in Africa: Evidence From the H3Africa CHAIR Study.

Hypertension and obesity are the most important modifiable risk factors for cardiovascular diseases, but their association is not well characterized in Africa. We investigated regional patterns and association of obesity with hypertension among 30 044 continental Africans. We harmonized data on hypertension (defined as previous diagnosis/use of antihypertensive drugs or blood pressure [BP]≥140/90 mmHg/BP≥130/80 mmHg) and obesity from 30 044 individuals in the Cardiovascular H3Africa Innovation Resource across 13 African countries. We analyzed data from population-based controls and the Entire Harmonized Dataset. Age-adjusted and crude proportions of hypertension were compared regionally, across sex, and between hypertension definitions. Logit generalized estimating equation was used to determine the independent association of obesity with hypertension (P value <5%). Participants were 56% women; with mean age 48.5±12.0 years. Crude proportions of hypertension (at BP≥140/90 mmHg) were 47.9% (95% CI, 47.4-48.5) for Entire Harmonized Dataset and 42.0% (41.1-42.7) for population-based controls and were significantly higher for the 130/80 mm Hg threshold at 59.3% (58.7-59.9) in population-based controls. The age-adjusted proportion of hypertension at BP≥140/90 mmHg was the highest among men (33.8% [32.1-35.6]), in western Africa (34.7% [33.3-36.2]), and in obese individuals (43.6%; 40.3-47.2). Obesity was independently associated with hypertension in population-based controls (adjusted odds ratio, 2.5 [2.3-2.7]) and odds of hypertension in obesity increased with increasing age from 2.0 (1.7-2.3) in younger age to 8.8 (7.4-10.3) in older age. Hypertension is common across multiple countries in Africa with 11.9% to 51.7% having BP≥140/90 mmHg and 39.5% to 69.4% with BP≥130/80 mmHg. Obese Africans were more than twice as likely to be hypertensive and the odds increased with increasing age.

AAV-Mediated Expression of Broadly Neutralizing and Vaccine-like Antibodies Targeting the HIV-1 Envelope V2 Region.

HIV-1 infection continues to be a global health challenge and a vaccine is urgently needed. Broadly neutralizing antibodies (bNAbs) are considered essential as they inhibit multiple HIV-1 strains, but they are difficult to elicit by conventional immunization. In contrast, non-neutralizing antibodies that correlated with reduced risk of infection in the RV144 HIV vaccine trial are relatively easy to induce, but responses are not durable. To overcome these obstacles, adeno-associated virus (AAV) vectors were used to provide long-term expression of antibodies targeting the V2 region of the HIV-1 envelope protein, including the potent CAP256-VRC26.25 bNAb, as well as non-neutralizing CAP228 antibodies that resemble those elicited by vaccination. AAVs mediated effective antibody expression in cell culture and immunocompetent mice. Mean concentrations of human immunoglobulin G (IgG) in mouse sera increased rapidly following a single AAV injection, reaching 8-60 µg/mL for CAP256 antibodies and 44-220 µg/mL for CAP228 antibodies over 24 weeks, but antibody concentrations varied for individual mice. Secreted antibodies collected from serum retained the expected binding and neutralizing activity. The vectors generated here are, therefore, suitable for the delivery of V2-targeting HIV antibodies, and they could be used in a vectored immunoprophylaxis (VIP) approach to sustain the level of antibody expression required to prevent HIV infection.

Classical Cardiovascular Risk Factors and HIV are Associated With Carotid Intima-Media Thickness in Adults From Sub-Saharan Africa: Findings From H3Africa AWI-Gen Study.

Background Studies on the determinants of carotid intima-media thickness ( CIMT ), a marker of sub-clinical atherosclerosis, mostly come from white, Asian, and diasporan black populations. We present CIMT data from sub-Saharan Africa, which is experiencing a rising burden of cardiovascular diseases and infectious diseases. Methods and Results The H3 (Human Hereditary and Health) in Africa's AWI-Gen (African-Wits-INDEPTH partnership for Genomic) study is a cross-sectional study conducted in adults aged 40 to 60 years from Burkina Faso, Kenya, Ghana, and South Africa. Cardiovascular disease risk and ultrasonography of the CIMT of right and left common carotids were measured. Multivariable linear and mixed-effect multilevel regression modeling was applied to determine factors related to CIMT. Data included 8872 adults (50.8% men), mean age of 50±6 years with age- and sex-adjusted mean (±SE) CIMT of 640±123µm. Participants from Ghana and Burkina Faso had higher CIMT compared with other sites. Age (ß = 6.77, 95%CI [6.34-7.19]), body mass index (17.6[12.5-22.8]), systolic blood pressure (7.52[6.21-8.83]), low-density lipoprotein cholesterol (5.08[2.10-8.06]) and men (10.3[4.75- 15.9]) were associated with higher CIMT. Smoking was associated with higher CIMT in men. High-density lipoprotein cholesterol (-12.2 [-17.9- -6.41]), alcohol consumption (-13.5 [-19.1--7.91]) and HIV (-8.86 [-15.7--2.03]) were inversely associated with CIMT. Conclusions Given the rising prevalence of cardiovascular diseases risk factors in sub-Saharan Africa, atherosclerotic diseases may become a major pan-African epidemic unless preventive measures are taken particularly for prevention of hypertension, obesity, and smoking. HIV -specific studies are needed to fully understand the association between HIV and CIMT in sub-Saharan Africa.

Regional and sex-specific variation in BMI distribution in four sub-Saharan African countries: The H3Africa AWI-Gen study.

BACKGROUND: African populations are characterised by diversity at many levels including: demographic history, genetic ancestry, language, wealth, socio-political landscape, culture and behaviour. Several of these have a profound impact on body fat mass. Obesity, a key risk factor for cardiovascular and metabolic diseases, in the wake of the epidemiological and health transitions across the continent, requires detailed analysis together with other major risk factors. OBJECTIVE: To compare regional and sex-specific body mass index (BMI) distributions, using a cross-sectional study design, in adults aged 40-60 years across six study sites in four sub-Saharan African (SSA) countries and to compare the determinants of BMI at each. METHODS: Anthropometric measurements were standardised across sites and BMI calculated. Median BMI and prevalence of underweight, lean, overweight and obesity were compared between the sexes and across sites. Data from multivariable linear regression models for the principal determinants of BMI were summarised from the site-specific studies. RESULTS: BMI was calculated in 10,702 participants (55% female) and was significantly higher in women than men at nearly all sites. The highest prevalence of obesity was observed at the three South African sites (42.3-66.6% in women and 2.81-17.5% in men) and the lowest in West Africa (1.25-4.22% in women and 1.19-2.20% in men). Across sites, higher socio-economic status and educational level were associated with higher BMI. Being married and increased dietary intake were associated with higher BMI in some communities, whilst smoking and alcohol intake were associated with lower BMI, as was HIV infection in the regions where it was prevalent. CONCLUSION: In SSA there is a marked variation in the prevalence of obesity both regionally and between men and women. Our data suggest that the drive for social upliftment within Africa will be associated with rising levels of obesity, which will require the initiation of targeted sex-specific intervention programmes across specific African communities.

Genomic and environmental risk factors for cardiometabolic diseases in Africa: methods used for Phase 1 of the AWI-Gen population cross-sectional study.

There is an alarming tide of cardiovascular and metabolic disease (CMD) sweeping across Africa. This may be a result of an increasingly urbanized lifestyle characterized by the growing consumption of processed and calorie-dense food, combined with physical inactivity and more sedentary behaviour. While the link between lifestyle and public health has been extensively studied in Caucasian and African American populations, few studies have been conducted in Africa. This paper describes the detailed methods for Phase 1 of the AWI-Gen study that were used to capture phenotype data and assess the associated risk factors and end points for CMD in persons over the age of 40 years in sub-Saharan Africa (SSA). We developed a population-based cross-sectional study of disease burden and phenotype in Africans, across six centres in SSA. These centres are in West Africa (Nanoro, Burkina Faso, and Navrongo, Ghana), in East Africa (Nairobi, Kenya) and in South Africa (Agincourt, Dikgale and Soweto). A total of 10,702 individuals between the ages of 40 and 60 years were recruited into the study across the six centres, plus an additional 1021 participants over the age of 60 years from the Agincourt centre. We collected socio-demographic, anthropometric, medical history, diet, physical activity, fat distribution and alcohol/tobacco consumption data from participants. Blood samples were collected for disease-related biomarker assays, and genomic DNA extraction for genome-wide association studies. Urine samples were collected to assess kidney function. The study provides base-line data for the development of a series of cohorts with a second wave of data collection in Phase 2 of the study. These data will provide valuable insights into the genetic and environmental influences on CMD on the African continent.

Regional and Sex Differences in the Prevalence and Awareness of Hypertension: An H3Africa AWI-Gen Study Across 6 Sites in Sub-Saharan Africa.

BACKGROUND: There is a high prevalence of hypertension and related cardiovascular diseases in sub-Saharan Africa, yet few large studies exploring hypertension in Africa are available. The actual burden of disease is poorly understood and awareness and treatment to control it is often suboptimal. OBJECTIVES: The study sought to report the prevalence of measured hypertension and to assess awareness and control of blood pressure among older adults in rural and urban settings in 6 sites located in West, East, and Southern Africa. In addition, we examined regional, sex, and age differences related to hypertension. METHODS: A population-based cross-sectional study was performed at 6 sites in 4 African countries: Burkina Faso (Nanoro), Ghana (Navrongo), Kenya (Nairobi), and South Africa (Agincourt, Dikgale, Soweto). Blood pressure measurements were taken using standardized procedures on 10,696 adults 40 to 60 years of age. Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or taking antihypertensive medication. RESULTS: The mean prevalence of hypertension ranged from 15.1% in Nanoro to 54.1% in Soweto. All 3 of the South African sites had a mean prevalence of hypertension of over 40.0%, significantly higher than in Nairobi (25.6%) and Navrongo (24.5%). Prevalence increased with age in both sexes and at all sites. A significantly higher prevalence of hypertension was observed in women in Agincourt, Dikgale, and Nairobi, whereas in Nanoro this trend was reversed. Within the hypertensive group the average proportion of participants who were aware of their blood pressure status was only 39.4% for men and 53.8% for women, and varied widely across sites. CONCLUSIONS: Our study demonstrates that the prevalence of hypertension and the level of disease awareness differ not only between but also within sub-Saharan African countries. Each nation must tailor their regional hypertension awareness and screening programs to match the characteristics of their local populations.

The therapeutic application of CRISPR/Cas9 technologies for HIV.

INTRODUCTION: The use of antiretroviral therapy has led to a significant decrease in morbidity and mortality in HIV-infected individuals. Nevertheless, gene-based therapies represent a promising therapeutic paradigm for HIV-1, as they have the potential for sustained viral inhibition and reduced treatment interventions. One new method amendable to a gene-based therapy is the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) gene editing system. AREAS COVERED: CRISPR/Cas9 can be engineered to successfully modulate an array of disease-causing genetic elements. We discuss the diverse roles that CRISPR/Cas9 may play in targeting HIV and eradicating infection. The Cas9 nuclease coupled with one or more small guide RNAs can target the provirus to mediate excision of the integrated viral genome. Moreover, a modified nuclease-deficient Cas9 fused to transcription activation domains may induce targeted activation of proviral gene expression allowing for the purging of the latent reservoirs. These technologies can also be exploited to target host dependency factors such as the co-receptor CCR5, thus preventing cellular entry of the virus. EXPERT OPINION: The diversity of the CRISPR/Cas9 technologies offers great promise for targeting different stages of the viral life cycle, and have the capacity for mediating an effective and sustained genetic therapy against HIV.