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- Prevalência de fibrilhação auricular na Província do Bengo, Angola: resultados de um estudo de base populacionalPublication . Gonçalves, Mauer A. A.; Pedro, João Mário; Silva, Carina; Magalhães, Pedro; Brito, MiguelIntrodução: A fibrilhação auricular é a arritmia sustentada mais comum na população adulta com significado clínico, representando um importante problema de saúde pública. Não existe na literatura dados publicados acerca da prevalência da fibrilhação auricular em Angola. Objetivo: O presente estudo foi realizado com o objetivo de determinar a prevalência de fibrilhação auricular numa população do Bengo, uma província do norte de Angola, estratificada por sexo e idade e análise da sua relação com alguns fatores de risco cardiovascular. Materiais e Métodos: Os dados são provenientes do estudo CardioBengo, um estudo transversal de base comunitária, do qual foi selecionada uma amostra aleatória de indivíduos com idades compreendidas entre os 15 e os 84 anos. No total foram incluídos 2 379 indivíduos na análise final. Resultados: A idade média dos participantes foi de 35 anos e 63% da amostra era do sexo feminino. Verificou-se que a frequência de consumo de álcool era de 35,8%, a prevalência de acidente vascular isquémico ou acidente isquémico transitório foi de 0,4%; insuficiência cardíaca congestiva, 0,3%; doença cardíaca isquémica, 0,3% e hipertrofia ventricular esquerda, 37,2%. A fibrilhação auricular foi identificada em dois indivíduos, o que representa uma prevalência de 0,084%. Conclusão: O nosso estudo mostra uma baixa prevalência de fibrilhação auricular, quando comparada com as encontradas em estudos realizados em países desenvolvidos, mas semelhante à encontrada em estudos da África Subsariana.
- Are genetic modifiers the answer to different responses to hydroxyurea treatment? A pharmacogenetic study in sickle cell anemia Angolan childrenPublication . Ginete, Catarina; Delgadinho, Mariana; Santos, Brígida; Pinto, Vera; Silva, Carina; Miranda, Armandina; Brito, MiguelSickle cell anemia (SCA) is an inherited disease affecting the hemoglobin that is particularly common in sub-Saharan Africa. Although monogenic, phenotypes are markedly heterogeneous in terms of severity and life span. Hydroxyurea is still the most common treatment for these patients, and the response to treatment is highly variable and seems to be an inherited trait. Therefore, identifying the variants that might predict hydroxyurea response is important for identifying patients who will have a poorer or non-response to treatment, and the ones that are more prone to suffer from severe side effects. In the present pharmacogenetic study, we analyzed the exons of 77 genes described in the literature as potentially associated with hydroxyurea metabolism in Angolan children treated with hydroxyurea and evaluated the drug response considering fetal hemoglobin levels, other hematological and biochemical parameters, hemolysis, number of vaso-occlusive crises and hospitalizations. Thirty variants were identified in 18 of those genes as possibly associated with drug response, five of them in gene DCHS2. Other polymorphisms in this gene were also associated with hematological, biochemical, and clinical parameters. Further research examining the maximum tolerated dose and fixed-dose with a larger sample size is necessary to corroborate these findings.
- Normal limits of the electrocardiogram in AngolansPublication . Gonçalves, Mauer; Pedro, João Mário; Silva, Carina; Magalhães, Pedro; Brito, MiguelIntroduction: Studies on the normal electrocardiogram limits in African populations are limited, especially in sub-Saharan Africa. There is no literature describing normal ECG limits in Angolans. Objectives: The aim of this study is to establish the normal ECG limits for adult Angolans, without established heart disease, stratified by gender and age. Methods: A cross-sectional study was performed, involving 2179 participants from a population in northern Angola, without established heart disease, aged between 15 and 74 years. A 12‑lead ECG and a rhythm strip were recorded for all participants and analyzed and processed by the University of Glasgow software and encoded by the Minnesota Code. The normal range of the electrocardiographic parameters was established as the 2nd and 98th percentiles of the measurement distribution per age group and gender. Mann-Whitney and Kruskal-Wallis tests were used for two independent groups and Bonferroni adjustments were used for multiple testing. GAMLSS models were used to obtain the continuous age-dependent percentile curves. Results: The normal range of the ECG differed between men and women: heart rate 49 to 100 bpm vs. 55 to 108 bpm, P wave duration 81 to 130 ms vs. 84 to 130 ms, PR interval 119 to 210 ms vs. 120 to 202 ms, QRS duration 74 to 110 ms vs. 70 to 104 ms, QT interval 324 to 441 ms vs. 314 and 438 ms, P-wave axis − 29 to 850 vs. -18 to 810, QRS-wave axis − 13 to 850 vs. -180 and 820, T-wave axis 0 to 720 vs. -8 to 730, Sokolow-Lyon index 2.13 to 6.21 mV vs. 1.60 to 4.87 mV, Cornell index 0.17 to 6.24 mV vs. 0.14 mV to 4.35 mV. Conclusions: The values described for the electrocardiographic measurements above can act as a reference framework for Angolan adults without established heart disease. Our study suggests that the normal range of most ECG parameters varies according to age and sex and the ECG diagnostic criteria must therefore be specific for these demographic measures.
- How hydroxyurea alters the gut microbiome: a longitudinal study involving Angolan children with sickle cell anemiaPublication . Delgadinho, Mariana; Ginete, Catarina; Santos, Brígida; Fernandes, Carolina; Silva, Carina; Miranda, Armandina; Vasconcelos, Jocelyne Neto de; Brito, MiguelSickle cell anemia (SCA) is an inherited hematological disorder and a serious global health problem, especially in Sub-Saharan Africa. Although hydroxyurea (HU) is the leading treatment for patients with SCA, its effects on the gut microbiome have not yet been explored. In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment. A total of 66 stool samples were obtained and sequenced for the 16S rRNA gene (V3-V4 regions). Significant associations were observed in alpha and beta-diversity, with higher values of species richness for the children naïve for HU. We also noticed that children after HU had higher proportions of several beneficial bacteria, mostly short-chain fatty acids (SCFAs) producing species, such as Blautia luti, Roseburia inulinivorans, Eubacterium halli, Faecalibacterium, Ruminococcus, Lactobacillus rogosae, among others. In addition, before HU there was a higher abundance of Clostridium_g24, which includes C. bolteae and C. clostridioforme, both considered pathogenic. This study provides the first evidence of the HU effect on the gut microbiome and unravels several microorganisms that could be considered candidate biomarkers for disease severity and HU efficacy.
- Prevalence of major and minor electrocardiographic abnormalities and their relationship with cardiovascular risk factors in AngolansPublication . Gonçalves, Mauer A. A.; Pedro, João Mário; Silva, Carina; Magalhães, Pedro; Brito, MiguelAims: To identify the prevalence of major and minor electrocardiographic abnormalities and their association with the main risk factors for cardiovascular disease in a population in the province of Bengo, northern Angola. Methods: A cross-sectional community-based study was conducted and a representative random sample stratified by sex and age was selected. In total, 2379 black individuals were included in the final analysis. A standard 12-lead ECG was recorded from all participants, analyzed and processed by the University of Glasgow software, and coded by the Minnesota code. Results: 22.3% of participants had minor electrocardiographic abnormalities and 4.58% major ECG abnormalities. The most common minor ECG abnormalities were abnormal T wave inversion, minor isolated ST abnormalities, and premature beats. The most common major ECG abnormalities were Left ventricular hypertrophy with major ST-T abnormalities, Ventricular conduction defects, and major Q-wave abnormalities. Hypertension, diabetes mellitus, hypercholesterolemia, alcohol consumption, and smoking, were significantly associated with major and minor electrocardiographic abnormalities. Conclusions: In this study, several participants had minor and major electrocardiographic abnormalities. Minor electrocardiographic abnormalities were more prevalent in men and major abnormalities in women. The electrocardiographic abnormalities had significant associations with the main cardiovascular risk factors.
- Normal values of the electrocardiogram in AngolansPublication . Gonçalves, Mauer; Pedro, João Almeida; Silva, Carina; Magalhães, Pedro; Brito, MiguelIntroduction: Studies on the normal electrocardiogram limits in African populations are limited, especially in sub-Saharan Africa. There is no literature describing normal ECG limits in Angolans. Objectives: The aim of this study is to establish the normal ECG values for adult Angolans, without established heart disease, stratified by gender and age.
- Influence of cigarette smoking on the Index of Cardiac Electrophysiological Balance in apparently healthy AngolansPublication . Gonçalves, Mauer; Pedro, João Mário; Silva, Carina; Magalhães, Pedro; Brito, MiguelBackground: Tobacco use accelerates atherosclerosis and is one of the predictors of death from ischemic heart disease, arrhythmias, heart failure, and sudden death. A new non-invasive parameter, the Index of Cardiac Electrophysiological Balance (iCEB) between depolarization and repolarization of the action potential, was considered a new biomarker for the identification of patients at increased arrhythmic risk. Objectives: We aimed to evaluate the iCEB in apparently healthy Angolans with habitual cigarette smoking compared to non-smokers. Subjects and methods: Data were obtained from the CardioBengo study, a cross-sectional community-based study in which a random sample of individuals aged between 15 and 84 years was selected. In total, 214 healthy subjects, 102 smokers, and 112 non-smokers in the same age group were included in the final analysis. Results: The average age of the participants was 42.17±13.04 years old and 26.6% of the sample was female. Smoking subjects had higher iCEB and corrected Index of Cardiac Electrophysiological Balance (iCEBc) values compared with non-smoking controls (4.39 vs. 4.25; p=0.024, respectively), and (4.74 vs. 4.57; p=0.030, respectively). Conclusions: In summary, iCEB and iCEBc were significantly higher in habitual smokers than in nonsmokers, which represents an increased risk of ventricular arrhythmogenesis in healthy habitual smokers. To the best of our knowledge, this is the first study performed in Africa to evaluate iCEB in smokers, making this type of study very important in low- and middle-income countries in the context of epidemiological transition.
- Genetic modifiers of sickle cell anemia phenotype in a cohort of Angolan childrenPublication . Ginete, Catarina; Delgadinho, Mariana; Santos, Brígida; Miranda, Armandina; Silva, Carina; Guerreiro, Paulo; Chimusa, Emile R.; Brito, MiguelThis study aimed to identify genetic markers in the HBB Cluster; HBS1L-MYB intergenic region; and BCL11A, KLF1, FOX3, and ZBTB7A genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using the next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hematological, biochemical, and clinical data were considered to determine patients’ severity phenotypes. Samples from 192 patients were sequenced, and 5,019,378 variants of high quality were registered. A catalog of candidate modifier genes that clustered in pathophysiological pathways important for SCA was generated, and candidate genes associated with increasing vaso-occlusive crises (VOC) and with lower fetal hemoglobin (HbF) were identified. These data support the polygenic view of the genetic architecture of SCA phenotypic variability. Two single nucleotide polymorphisms in the intronic region of 2q16.1, harboring the BCL11A gene, are genome-wide and significantly associated with decreasing HbF. A set of variants was identified to nominally be associated with increasing VOC and are potential genetic modifiers harboring phenotypic variation among patients. To the best of our knowledge, this is the first investigation of clinical variation in SCA in Angola using a well-customized and targeted sequencing approach.
- Electrocardiographic findings in pregnant women in AngolaPublication . Gonçalves, Mauer A. A.; Pedro, João Mário; Silva, Carina; Magalhães, Pedro; Brito, MiguelBackground: Studies on the electrocardiogram findings in African pregnant women are limited. There is no information available in the literature on the electrocardiographic parameters of pregnant Angolan women. Objectives: The aim of this study was to describe electrocardiographic findings in women with normal pregnancies in Bengo Province, Angola. Methods: This is a community-based study with a cross-sectional design conducted between September 2013 and March 2014 in Bengo. The study involved 114 black pregnant women, compared with a paired control group comprising 120 black non-pregnant women, aged 15 to 42 years. A 12-lead electrocardiogram and a rhythm strip were recorded for all participants. Results: In this study, the mean age was 26.2 ± 7.3 years. Comparing pregnant women vs. non-pregnant, we found the following mean values: Heart rate (83 bpm vs. 74 bpm, p < .001), PR interval (146 ms vs. 151 ms, p = .034), QT interval (360 ms vs. 378 ms, p < .001), QTIc Fridericia (398 ms vs. 403, p = .017), QTIc Framingham (399 ms vs. 404 ms, p = .013) and T-wave axis (340 vs. 410, p = .001).The main electrocardiographic changes found were: Sinus tachycardia (4.4% vs. 2.5%), T-wave inversion (14.9% vs. 1.7%), Minor ST segment depression (4.5% vs. 0%) and left ventricular hypertrophy (11.4% vs. 11.7%, p = .726). Conclusions: Pregnant Angolan women compared with controls, had several significantly higher values for heart rate, and significantly lower values of systolic blood pressure and diastolic blood pressure, PR interval, QT interval, QTc interval by Fridericia and Framingham, and T-wave axis. Sinus tachycardia, T-wave inversion, and left ventricular hypertrophy, were the main electrocardiographic changes found.