Rationale, Design, and the Baseline Characteristics of the RHDGen (The Genetics of Rheumatic Heart Disease) Network Study†.

BACKGROUND: The genetics of rheumatic heart disease (RHDGen) Network was developed to assist the discovery and validation of genetic variations and biomarkers of risk for rheumatic heart disease (RHD) in continental Africans, as a part of the global fight to control and eradicate rheumatic fever/RHD. Thus, we describe the rationale and design of the RHDGen study, comprising participants from 8 African countries. METHODS: RHDGen screened potential participants using echocardiography, thereafter enrolling RHD cases and ethnically-matched controls for whom case characteristics were documented. Biological samples were collected for conducting genetic analyses, including a discovery case-control genome-wide association study (GWAS) and a replication trio family study. Additional biological samples were also collected, and processed, for the measurement of biomarker analytes and the biomarker analyses are underway. RESULTS: Participants were enrolled into RHDGen between December 2012 and March 2018. For GWAS, 2548 RHD cases and 2261 controls (3301 women [69%]; mean age [SD], 37 [16.3] years) were available. RHD cases were predominantly Black (66%), Admixed (24%), and other ethnicities (10%). Among RHD cases, 34% were asymptomatic, 26% had prior valve surgery, and 23% had atrial fibrillation. The trio family replication arm included 116 RHD trio probands and 232 parents. CONCLUSIONS: RHDGen presents a rare opportunity to identify relevant patterns of genetic factors and biomarkers in Africans that may be associated with differential RHD risk. Furthermore, the RHDGen Network provides a platform for further work on fully elucidating the causes and mechanisms associated with RHD susceptibility and development.

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals: Findings From the RHDGen Study.

Importance: Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD. Objective: To identify common genetic loci associated with RHD susceptibility in Black African individuals. Design, Setting, and Participants: This multicenter case-control genome-wide association study (GWAS), the Genetics of Rheumatic Heart Disease, examined more than 7 million genotyped and imputed single-nucleotide variations. The 4809 GWAS participants and 116 independent trio families were enrolled from 8 African countries between December 31, 2012, and March 31, 2018. All GWAS participants and trio probands were screened by use of echocardiography. Data analyses took place from May 15, 2017, until March 14, 2021. Main Outcomes and Measures: Genetic associations with RHD. Results: This study included 4809 African participants (2548 RHD cases and 2261 controls; 3301 women [69%]; mean [SD] age, 36.5 [16.3] years). The GWAS identified a single RHD risk locus, 11q24.1 (rs1219406 [odds ratio, 1.65; 95% CI, 1.48-1.82; P = 4.36 × 10-8]), which reached genome-wide significance in Black African individuals. Our meta-analysis of Black (n = 3179) and admixed (n = 1055) African individuals revealed several suggestive loci. The study also replicated a previously reported association in Pacific Islander individuals (rs11846409) at the immunoglobulin heavy chain locus, in the meta-analysis of Black and admixed African individuals (odds ratio, 1.16; 95% CI, 1.06-1.27; P = 1.19 × 10-3). The HLA (rs9272622) associations reported in Aboriginal Australian individuals could not be replicated. In support of the known polygenic architecture for RHD, overtransmission of a polygenic risk score from unaffected parents to affected probands was observed (polygenic transmission disequilibrium testing mean [SE], 0.27 [0.16] SDs; P = .04996), and the chip-based heritability was estimated to be high at 0.49 (SE = 0.12; P = 3.28 × 10-5) in Black African individuals. Conclusions and Relevance: This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.

Sodium content of bread from bakeries in Maputo, Mozambique: trends between 2012 and 2018.

OBJECTIVE: To assess the Na content and price of bread available in bakeries in the city of Maputo in 2018 and describe trends since 2012. DESIGN: Cross-sectional evaluation of bread sold in twenty bakeries in the city of Maputo. Three loaves of white and three loaves of brown bread were collected from each bakery when available, and Na contents were quantified by flame photometry. To assess trends, samples of white bread collected in 2012 and analysed using the same methodology were compared with samples of white bread collected in 2018 from the same bakeries. SETTING: City of Maputo, capital of Mozambique. RESULTS: In 2018, the mean (range) Na content in mg/100 g of white and brown breads were 419·1 (325·4-538·8) and 389·8 (248·0-609·0), respectively. Non-compliance with Na targets in bread according to the South African regulation (<380 mg/100 g) was observed in 70 % of white and 43 % of brown bread samples. A total of twelve bakeries had samples evaluated in both 2012 and 2018; among these, the mean Na content in white bread decreased by just over 10 % - the mean difference (95 % CI) was 46·6 mg/100 g (1·7, 91·5); and there was a significant increase of 3·7-5·4 meticais in the mean price per 100 g of white bread. CONCLUSIONS: The Na content of bread available in bakeries in the city of Maputo decreased in recent years despite the absence of a specific regulation in Mozambique.

Blood pressure screening in Mozambique: the May Measurement Month 2017 project-Sub-Saharan Africa.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. In Mozambique, two national surveys of risk factors for chronic diseases were done, using the WHO STEPWISE approach, the first in 2005 and the last in 2014/2015. In this period of 10 years, the prevalence of hypertension in the adult population increased from 33.1% to 38.9% and the extremely low levels of awareness, treatment, and control did not change significantly. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Screening was conducted by volunteers, mainly in work places, markets, and religious activities, in the capital city, in most of the provincial capitals and some rural districts. About 4454 individuals were screened with a mean age of 39 years, and, after multiple imputation, 1371 (31.1%) had hypertension. Of individuals not receiving anti-hypertensive medication, 1099 (26.6%) were hypertensive. Of individuals receiving antihypertensive medication, 166 (61.6%) had uncontrolled BP. MMM17 was the largest BP screening campaign undertaken in Mozambique. These results suggest that opportunistic screening is an important tool to identify significant numbers of patients with raised BP.

Urinary Sodium and Potassium Excretion and Dietary Sources of Sodium in Maputo, Mozambique.

This study aimed to evaluate the urinary excretion of sodium and potassium, and to estimate the main food sources of sodium in Maputo dwellers. A cross-sectional evaluation of a sample of 100 hospital workers was conducted between October 2012 and May 2013. Sodium and potassium urinary excretion was assessed in a 24-h urine sample; creatinine excretion was used to exclude unlikely urine values. Food intake in the same period of urine collection was assessed using a 24-h dietary recall. The Food Processor Plus® was used to estimate sodium intake corresponding to naturally occurring sodium and sodium added to processed foods (non-discretionary sodium). Salt added during culinary preparations (discretionary sodium) was computed as the difference between urinary sodium excretion and non-discretionary sodium. The mean (standard deviation) urinary sodium excretion was 4220 (1830) mg/day, and 92% of the participants were above the World Health Organization (WHO) recommendations. Discretionary sodium contributed 60.1% of total dietary sodium intake, followed by sodium from processed foods (29.0%) and naturally occurring sodium (10.9%). The mean (standard deviation) urinary potassium excretion was 1909 (778) mg/day, and 96% of the participants were below the WHO potassium intake recommendation. The mean (standard deviation) sodium to potassium molar ratio was 4.2 (2.4). Interventions to decrease sodium and increase potassium intake are needed in Mozambique.

Sodium content of bread from bakeries and traditional markets in Maputo, Mozambique.

OBJECTIVE: The Na content of bread is one of the most common targets of initiatives to reduce Na intake worldwide. Assessing the Na content of staple foods is of major relevance in Mozambique, given the high burden of hypertension in this setting. We aimed to estimate the Na content of white bread available in different bakeries and markets in Maputo. DESIGN: A cross-sectional study of the Na content of white bread available for sale at twenty-five bakeries and markets in Mozambique. Flame photometry was used to quantify the Na content of the bread. The percentage of samples meeting manufacturer Na targets from South Africa and six countries from other regions, selected as benchmarks, was computed. SETTING: Maputo, Mozambique. SUBJECTS: Three loaves of white bread from each selected bakery/market. RESULTS: The mean Na content of bread was 450.3 mg/100 g (range: 254.9-638.3 mg/100 g), with no significant differences between bakeries and traditional markets. Most samples (88 %) did not meet the regulation in South Africa (≤ 380 mg/100 g). When considering the targets from other countries (range: ≤ 360-550 mg/100 g), the prevalence of non-compliance varied between 8 % and 92 %. There were no significant differences in the price of bread with Na content below and above the targets. CONCLUSIONS: The content of Na in bread varies widely in Mozambique, reaching high values in a high proportion of the bakeries and markets in Maputo. Measures to regulate the Na content in bread may contribute to a reduction in Na intake and improved health at the population level.