Research in industrialized countries has demonstrated that a key factor limiting the control of hypertension is poor patient adherence and that the most successful interventions for long-term ...adherence employ multiple strategies. Very little data exist on this question in low-income countries, wherein medication-taking behavior may be less well developed.
We conducted a treatment adherence trial of 544 patients mean age ∼63 years, mean blood pressure (BP) ∼168/92 mmHg with previously untreated hypertension in urban and rural Nigeria. Eligible participants were randomized to one of two arms: clinic management only, or clinic management and home visits. Both interventions included three elements: a community based, nurse-led treatment program with physician backup; facilitation of clinic visits and health education; and the use of diuretics and a β blocker as needed. After initial diagnosis, the management protocol was implemented by a nurse with physician backup. Participants were evaluated monthly for 6 months.
Medication adherence was assessed with pill count and urine testing. Drop-out rates, by treatment group, ranged from 12 to 28%. Among participants who completed the 6-month trial, overall adherence was high (∼77% of participants took >98% of prescribed pills). Adherence did not differ by treatment arm, but was better at the rural than the urban site and among those with higher baseline BP. Hypertension control (BP <140/90 mmHg) was achieved in approximately 66% of participants at 6 months.
This community-based intervention confirms relatively modest default rates compared with industrialized societies, and suggests that medication adherence can be high in developing world settings in clinic attenders.
The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a ...role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (FST < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 × 10−11) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers.
CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health ...in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age <1 to 74 years across a broad spectrum of kidney diseases secondary to hypertension-attributed nephropathy, diabetes, HIV infection, sickle cell disease, biopsy-proven glomerular disease, and CKD of unknown origin. Clinical and demographic data with biospecimens are collected to assess clinical, biochemical, and genetic markers of kidney disease. As of March 2015, a total of 3499 patients and controls have been recruited and 1897 had complete entry data for analysis. Slightly more than half (50.2%) of the cohort is female. Initial quality control of clinical data collection and of biosample and DNA analysis is satisfactory, demonstrating that a clinical research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa.
High blood pressure (BP) is the most common cardiovascular risk factor worldwide and a major contributor to heart disease and stroke. We previously discovered a BP-associated missense SNP (single ...nucleotide polymorphism)-rs2272996-in the gene encoding vanin-1, a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase. In the present study, we first replicated the association of rs2272996 and BP traits with a total sample size of nearly 30,000 individuals from the Continental Origins and Genetic Epidemiology Network (COGENT) of African Americans (P=0.01). This association was further validated using patient plasma samples; we observed that the N131S mutation is associated with significantly lower plasma vanin-1 protein levels. We observed that the N131S vanin-1 is subjected to rapid endoplasmic reticulum-associated degradation (ERAD) as the underlying mechanism for its reduction. Using HEK293 cells stably expressing vanin-1 variants, we showed that N131S vanin-1 was degraded significantly faster than wild type (WT) vanin-1. Consequently, there were only minimal quantities of variant vanin-1 present on the plasma membrane and greatly reduced pantetheinase activity. Application of MG-132, a proteasome inhibitor, resulted in accumulation of ubiquitinated variant protein. A further experiment demonstrated that atenolol and diltiazem, two current drugs for treating hypertension, reduce the vanin-1 protein level. Our study provides strong biological evidence for the association of the identified SNP with BP and suggests that vanin-1 misfolding and degradation are the underlying molecular mechanism.
The pathway-focused association approach offers a hypothesis driven alternative to the agnostic genome-wide association study. Here we apply the pathway-focused approach to an association study of ...hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in 1614 Nigerians with genome-wide data.
Testing of 28 pathways with biological relevance to hypertension, selected a priori, containing a total of 101 unique genes and 4,349 unique single-nucleotide polymorphisms (SNPs) showed an association for the adrenergic alpha 1 (ADRA1) receptor pathway with hypertension (p<0.0009) and diastolic blood pressure (p<0.0007). Within the ADRA1 pathway, the genes PNMT (hypertension P(gene)<0.004, DBP P(gene)<0.004, and SBP P(gene)<0.009, and ADRA1B (hypertension P(gene)<0.005, DBP P(gene)<0.02, and SBP P(gene)<0.02) displayed the strongest associations. Neither ADRA1B nor PNMT could be the sole mediator of the observed pathway association as the ADRA1 pathway remained significant after removing ADRA1B, and other pathways involving PNMT did not reach pathway significance.
We conclude that multiple variants in several genes in the ADRA1 pathway led to associations with hypertension and DBP. SNPs in ADRA1B and PNMT have not previously been linked to hypertension in a genome-wide association study, but both genes have shown associations with hypertension through linkage or model organism studies. The identification of moderately significant (10(-2)>p>10(-5)) SNPs offers a novel method for detecting the "missing heritability" of hypertension. These findings warrant further studies in similar and other populations to assess the generalizability of our results, and illustrate the potential of the pathway-focused approach to investigate genetic variation in hypertension.
Objectives:
This study sought to assess the current impact of health insurance coverage on medication adherence and blood pressure control of patients being managed for hypertension in Ghana and ...Nigeria.
Methods:
The study was a prospective study among 109 patients with hypertension in two health facilities with similar population dynamics in Ghana and Nigeria. Patients were systematically selected, categorized as having health insurance coverage or not, and followed up monthly for 6 months. The outcome variables (medication adherence and blood pressure control) were then measured and compared at 6 months. Analysis was done using Stata with level of significance set at p ⩽ 0.05.
Results:
There was a 90% insurance coverage among participants from Ghana compared to 15% from Nigeria. National Health Insurance Authority enrolees in both countries had better blood pressure control and medication adherence compared to non-enrolees (adjusted odds ratio = 2.6 and 4.5, respectively).
Conclusion:
National Health Insurance Authority enrolment was found to be poor among respondents in Nigeria compared to Ghana. Enrolment into the National health financing schemes in both countries led to better blood pressure control and medication adherence among patients with hypertension at primary health facilities. There is therefore the need for system strengthening to improve their sustainability.
Sequences up to several megabases in length have been found to be present in individual genomes but absent in the human reference genome. These sequences may be common in populations, and their ...absence in the reference genome may indicate rare variants in the genomes of individuals who served as donors for the human genome project. As the reference genome is used in probe design for microarray technology and mapping short reads in next generation sequencing (NGS), this missing sequence could be a source of bias in functional genomic studies and variant analysis. One End Anchor (OEA) and/or orphan reads from paired-end sequencing have been used to identify novel sequences that are absent in reference genome. However, there is no study to investigate the distribution, evolution and functionality of those sequences in human populations.
To systematically identify and study the missing common sequences (micSeqs), we extended the previous method by pooling OEA reads from large number of individuals and applying strict filtering methods to remove false sequences. The pipeline was applied to data from phase 1 of the 1000 Genomes Project. We identified 309 micSeqs that are present in at least 1% of the human population, but absent in the reference genome. We confirmed 76% of these 309 micSeqs by comparison to other primate genomes, individual human genomes, and gene expression data. Furthermore, we randomly selected fifteen micSeqs and confirmed their presence using PCR validation in 38 additional individuals. Functional analysis using published RNA-seq and ChIP-seq data showed that eleven micSeqs are highly expressed in human brain and three micSeqs contain transcription factor (TF) binding regions, suggesting they are functional elements. In addition, the identified micSeqs are absent in non-primates and show dynamic acquisition during primate evolution culminating with most micSeqs being present in Africans, suggesting some micSeqs may be important sources of human diversity.
76% of micSeqs were confirmed by a comparative genomics approach. Fourteen micSeqs are expressed in human brain or contain TF binding regions. Some micSeqs are primate-specific, conserved and may play a role in the evolution of primates.
Evidence-based task-strengthening strategies for hypertension (HTN) control (TASSH) are not readily available for patients living with HIV in sub-Saharan Africa where the dual burden of HTN and HIV ...remains high. We are conducting a cluster randomized controlled trial comparing the effectiveness of practice facilitation versus a self-directed control (i.e., receipt of TASSH with no practice facilitation) in reducing blood pressure and increasing the adoption of task-strengthening strategies for HTN control within HIV clinics in Nigeria. Prior to implementing the trial, we conducted formative research to identify factors that may influence the integration of TASSH within HIV clinics in Nigeria.
This mixed-methods study was conducted with purposively selected healthcare providers at 29 HIV clinics, followed by a 1-day stakeholder meeting with 19 representatives of HIV clinics. We collected quantitative practice assessment data using two instruments: (a) an adapted Service Availability and Readiness Assessment (SARA) tool to assess the capacity of the clinic to manage NCDs and (b) Implementation Climate Scale to assess the degree to which there is a strategic organizational climate supportive of the evidence-based practice implementation. The quantitative data were analyzed using descriptive statistics and measures of scale reliability. We also used the Consolidated Framework for Implementation Research (CFIR), to thematically analyze qualitative data generated and relevant to the aims of this study.
Across the 29 clinics surveyed, the focus on TASSH (mean=1.77 (SD=0.59)) and educational support (mean=1.32 (SD=0.68)) subscales demonstrated the highest mean score, with good-excellent internal consistency reliability (Cronbach's alphas ranging from 0.84 to 0.96). Within the five CFIR domains explored, the major facilitators of the intervention included relative advantage of TASSH compared to current practice, compatibility with clinic organizational structures, support of patients' needs, and intervention alignment with national guidelines. Barriers included the perceived complexity of TASSH, weak referral network and patient tracking mechanism within the clinics, and limited resources and diagnostic equipment for HTN.
Optimizing healthcare workers' implementation of evidence-based TASSH within HIV clinics requires attention to both the implementation climate and contextual factors likely to influence adoption and long-term sustainability. These findings have implications for the development of effective practice facilitation strategies to further improve the delivery and integration of TASSH within HIV clinics in Nigeria.
ClinicalTrials.gov , NCT04704336.
Hypertension is a major risk factor for all cardiovascular diseases, especially among African Americans. This study focuses on identifying specific blood pressure (BP) genes using 15 914 individuals ...of African ancestry from eight cohorts (Africa America Diabetes Mellitus, Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in young Adults, Genetics Network, Genetic Epidemiology Network of Arteriopathy, Howard University Family Study, Hypertension Genetic Epidemiology Network, and Loyola University Chicago Cohort) to further genetic findings in this population which has generally been underrepresented in BP studies.
We genotyped and performed various single variant and gene-based exome-wide analyses on 15 914 individuals on the Illumina HumanExome Beadchip v1.0 or v1.1 to test association with SBP and DBP long-term average residuals that were adjusted for age, age-squared, sex, and BMI.
We identified rare variants affecting SBP and DBP in 10 genes: AFF1, GAPDHS, SLC28A3, COL6A1, CRYBA2, KRBA1, SEL1L3, YOD1, CCDC13, and QSOX1. Prior experimental evidence for six of these 10 candidate genes supports their involvement in cardiovascular mechanisms, corroborating their potential roles in BP regulation.
Although our results require replication or validation due to their low numbers of carriers, and an ethnicity-specific genotyping array may be more informative, this study, which has identified several candidate genes in this population most susceptible to hypertension, presents one of the largest African-ancestry BP studies to date and the largest including analysis of rare variants.
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