Diversity of variant alleles encoding Kidd, Duffy, and Kell antigens in individuals with sickle cell disease using whole genome sequencing data from the NHLBI TOPMed Program.

BACKGROUND: Genetic variants in the SLC14A1, ACKR1, and KEL genes, which encode Kidd, Duffy, and Kell red blood cell antigens, respectively, may result in weakened expression of antigens or a null phenotype. These variants are of particular interest to individuals with sickle cell disease (SCD), who frequently undergo chronic transfusion therapy with antigen-matched units. The goal was to describe the diversity and the frequency of variants in SLC14A1, ACKR1, and KEL genes among individuals with SCD using whole genome sequencing (WGS) data. STUDY DESIGN AND METHODS: Two large SCD cohorts were studied: the Recipient Epidemiology and Donor Evaluation Study III (REDS-III) (n = 2634) and the Outcome Modifying Gene in SCD (OMG) (n = 640). Most of the studied individuals were of mixed origin. WGS was performed as part of the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program. RESULTS: In SLC14A1, variants included four encoding a weak Jka phenotype and five null alleles (JKnull ). JKA*01N.09 was the most common JKnull . One possible JKnull mutation was novel: c.812G>T. In ACKR1, identified variants included two that predicted Fyx (FY*X) and one corresponding to the c.-67T>C GATA mutation. The c.-67T>C mutation was associated with FY*A (FY*01N.01) in four participants. FY*X was identified in 49 individuals. In KEL, identified variants included three null alleles (KEL*02N.17, KEL*02N.26, and KEL*02N.04) and one allele predicting Kmod phenotype, all in heterozygosity. CONCLUSIONS: We described the diversity and distribution of SLC14A1, ACKR1, and KEL variants in two large SCD cohorts, comprising mostly individuals of mixed ancestry. This information may be useful for planning the transfusion support of patients with SCD.

Use of the National Heart, Lung, and Blood Institute Data Repository.

BACKGROUND: Research on data sharing from clinical trials has focused on elucidating perceptions, barriers, and attitudes among trialists and study participants with respect to sharing data. However, little information exists regarding utilization or associated publication of articles once clinical trial data have been widely shared. METHODS: We analyzed administrative records of investigator requests for data access, linked publications, and bibliometrics to describe the use of the National Heart, Lung, and Blood Institute data repository. RESULTS: From January 2000 through May 2016, a total of 370 investigators requested data from 1 or more clinical trials. Requests for trial data have been increasing, with 195 investigators (53%) initiating requests during the last 4.4 years of the study period. The predominant reason for requesting data was post hoc secondary analysis of new questions (72%), followed by analytic or statistical approaches to clinical trials (9%) and meta-analyses or pooled study research (7%). Of 172 requests with online project descriptions, only 2 requests were initiated for reanalysis of primary-outcome findings. Data from 88 of 100 available clinical trials were requested at least once, and the median time from repository availability to first request was 235 days. A total of 277 articles were published on the basis of data from 47 trials. Citation metrics from 224 articles indicated that half of the publications have cumulative citations that rank in the top 34% normalized for subject category and year of publication. CONCLUSIONS: Demand for trial data for secondary analysis has been increasing. Requesting data for the a priori purpose of reanalysis or verification of original findings was rare.

Hypertension Prevalence, Awareness, Treatment, and Control in Selected LMIC Communities: Results From the NHLBI/UHG Network of Centers of Excellence for Chronic Diseases.

BACKGROUND: Hypertension is the leading cause of cardiovascular disease and premature death worldwide. The prevalence of this public health problem is increasing in low- and middle-income countries (LMICs) in both urban and rural communities. OBJECTIVE: The aim of this study was to examine hypertension prevalence, awareness, treatment, and control in adults 35 to 74 years of age from urban and rural communities in LMICs in Africa, Asia, and South America. METHODS: The authors analyzed data from 7 population-based cross-sectional studies in selected communities in 9 LMICs that were conducted between 2008 and 2013. Age- and sex-standardized prevalence rates of pre-hypertension and hypertension were calculated. The prevalence rates of awareness, treatment, and control of hypertension were estimated overall and by subgroups of age, sex, and educational level. RESULTS: In selected communities, age- and sex-standardized prevalence rates of hypertension among men and women 35 to 74 years of age were 49.9% (95% confidence interval [CI]: 42.3% to 57.4%) in Kenya, 54.9% (95% CI: 51.3% to 58.4%) in South Africa, 52.5% (95% CI: 50.1% to 54.8%) in China, 32.5% (95% CI: 31.7% to 33.3%) in India, 42.3% (95% CI: 40.4% to 44.2%) in Pakistan, 45.4% (95% CI: 43.6% to 47.2%) in Argentina, 39.9% (95% CI: 37.8% to 42.1%) in Chile, 19.2% (95% CI: 17.8% to 20.5%) in Peru, and 44.1% (95% CI: 41.6% to 46.6%) in Uruguay. The proportion of awareness varied from 33.5% in India to 69.0% in Peru, the proportion of treatment among those who were aware of their hypertension varied from 70.8% in South Africa to 93.3% in Pakistan, and the proportion of blood pressure control varied from 5.3% in China to 45.9% in Peru. CONCLUSIONS: The prevalence of hypertension varies widely in different communities. The rates of awareness, treatment, and control also differ in different settings. There is a clear need to focus on increasing hypertension awareness and control in LMICs.

Building a platform for translational research in chronic noncommunicable diseases to address population health: lessons from NHLBI supported CRONICAS in Peru.

The CRONICAS Centre of Excellence in Chronic Diseases, based at Universidad Peruana Cayetano Heredia, was created in 2009 with support from the U.S. National Heart, Lung, and Blood Institute (NHLBI). The vision of CRONICAS is to build a globally recognized center of excellence conducting quality and innovative research and generating high-impact evidence for health. The center's identity is embedded in its core values: generosity, innovation, integrity, and quality. This review has been structured to describe the development of the CRONICAS Centre, with a focus on highlighting the ongoing translational research projects and capacity-building strategies. The CRONICAS Centre of Excellence is not a risk-averse organization: it benefits from past experiences, including past mistakes, and improves upon them and thus challenges traditional research approaches. This ethos and environment are key to fostering innovation in research.

Metabolic syndrome in Argentine women: ATPIII, IDF, IDF/AHA/NHLBI; what criterion should be used?

INTRODUCTION: The menopause and the metabolic syndrome (MS) are related with the increase of the risk of cardiovascular diseases. OBJECTIVES: To evaluate the existence of metabolic risk factors and the prevalence of MS in pre- and post-menopausal women. SUBJECTS: 253 women: 120 pre-menopausal and 133 post-menopausal. Anthropometric, arterial pressure and waist circumference measurements were carried out. Glycaemia, lipids, creatinine, hepatogram, uric acid and thyroid-stimulating hormone were dosed. RESULTS: Statistical higher registries of arterial pressure, levels of glycaemia, total cholesterol, low-density lipoprotein, triglycerides and TG/high-density lipoprotein relation were observed among post-menopausal patients. As regards this group, the MS diagnosis was considerably higher, being the same by all the criteria. CONCLUSIONS: We found more prevalence of cardiometabolic and MS risk factors among the group of post-menopausal patients. The responsible mechanisms would respond to the secondary hypoestrogenaemia at the cease of the ovarian function. Because of this fact, menopausal women should be considered a risk group for the development of MS.