Publications by authors named "Antonio Luiz P Ribeiro"

99 Publications

Accuracy and reliability of focused echocardiography in patients with Chagas disease from endemic areas: SaMi-Trop cohort study.

PLoS One 2021 4;16(11):e0258767. Epub 2021 Nov 4.

Postgraduate Course of Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

Background: Chagas disease remains a major cause of cardiovascular death in endemic areas. Focused echocardiography (FoCUS) is a point-of-care means of assessing cardiac function which can be useful for the diagnosis of cardiac involvement.

Objective: This study aims evaluating the characteristics of validity and reliability of FoCUS applied on Chagas disease patients.

Methods: Patients with Chagas disease coming from an endemic area were selected from a large cohort (SaMi-Trop). A simplified echocardiogram with only three images was extracted from the conventional echocardiogram performed in this cohort. The images were evaluated by an observer who was blinded to the clinical and echocardiographic data, to determine the accuracy and reliability of FoCUS for cardiac assessment. The analysis constituted of 5 prespecified variables, dichotomized in absence or presence: left ventricular (LV) size and systolic function, right ventricular (RV) size and systolic function, and LV aneurysm.

Results: We included 725 patients with a mean age of 63.4 ± 12.3 years, 483 (67%) female. Abnormal electrocardiogram was observed in 81.5% of the patients. Left and right ventricular dysfunctions were found in 103 (14%) and 49 (7%) of the patients, respectively. Sensitivity, specificity, positive predictive value and negative predictive value were 84%, 94%, 70% and 97% for LV enlargement and 81%, 93%, 68% and 97% for LV systolic dysfunction, respectively, and 46%, 99%, 60% and 98% for RV dilatation, and 37%, 100%, 100% and 96% for RV dysfunction, respectively. Inter and intraobserver agreement were 61% and 87% for LV enlargement and 63% and 92% for LV dysfunction, respectively, and 50% and 49% for RV size and 46% and 79% for RV dysfunction, respectively. LV apical aneurysm was found in 45 patients (6.2%) with the lowest sensitivity of FoCUS study (11%; 95% CI 2-28%).

Conclusions: FoCUS showed satisfactory values of validity and reliability for assessment of cardiac chambers in patients with Chagas disease, except for apical aneurysm. This tool can identify heart disease with potential impact on patient management in the limited-resource setting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258767PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568132PMC
November 2021

Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of -Seropositive Individuals.

Circulation 2021 Nov 27;144(19):1553-1566. Epub 2021 Sep 27.

Instituto de Medicina Tropical e Departamento de Moléstias Infecciosas e Parasitarias (L.F.B., E.C.S.), Faculdade de Medicina da Universidade de São Paulo, Brazil.

Background: There are few contemporary cohorts of -seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with seropositivity.

Methods: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as -seropositive blood donors. -seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, ECG, and echocardiogram at enrollment (2008-2010) and at follow-up (2018-2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration ≥120 ms, or both. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection.

Results: We enrolled 499 -seropositive donors (age 48±10 years, 52% male), 488 -seronegative donors (age 49±10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48±8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000 py (17/114, 15%) in -seropositive donors with cardiomyopathy at baseline. Among -seropositive donors without cardiomyopathy at baseline, mortality was 3.7 events/1000 py (15/385, 4%), which was no different from -seronegative donors with 3.6 deaths/1000 py (17/488, 3%). The incidence of cardiomyopathy in -seropositive donors was 13.8 (95% CI, 9.5-19.6) events/1000 py (32/262, 12%) compared with 4.6 (95% CI, 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with seropositivity of 9.2 (95% CI, 3.6-15.0) events/1000 py. antibody level at baseline was associated with development of cardiomyopathy (adjusted odds ratio, 1.4 [95% CI, 1.1-1.8]).

Conclusions: We present a comprehensive description of the natural history of seropositivity in a contemporary patient population. The results highlight the central importance of anti- antibody titer as a marker of Chagas disease activity and risk of progression.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578457PMC
November 2021

Outcomes of Echocardiography-Detected Rheumatic Heart Disease: Validating a Simplified Score in Cohorts From Different Countries.

J Am Heart Assoc 2021 09 17;10(18):e021622. Epub 2021 Sep 17.

The Heart InstituteCincinnati Childrens Hospital Medical Center, and the University of Cincinnati School of Medicine Cincinnati OH.

Background The natural history of latent rheumatic heart disease (RHD) detected by echocardiography remains unclear. We aimed to assess the accuracy of a simplified score based on the 2012 World Heart Federation criteria in predicting mid-term RHD echocardiography outcomes in children from 4 different countries. Methods and Results Patient-level baseline and follow-up data of children with latent RHD from 4 countries (Australia, n=62; Brazil, n=197; Malawi, n=40; New Zealand, n=94) were combined. A simplified echocardiographic scoring system previously developed from Brazilian and Ugandan cohorts, consisting of 5 point-based variables with respective weights, was applied: mitral valveanterior leaflet thickening (weight=3), excessive leaflet
tip motion (3), regurgitation jet length ≥2 cm (6), aortic valve
focal thickening (4), and any regurgitation (5). Unfavorable outcome was defined as worsening diagnostic category, persistent definite RHD or development/worsening of valve regurgitation/stenosis. The score model was updated using methods for recalibration. 393 patients (314 borderline, 79 definite RHD) with median follow-up of 36 (interquartile range, 25-48) months were included. Median age was 14 (interquartile range, 11-16) years and secondary prophylaxis was prescribed to 16%. The echocardiographic score model applied to this external population showed significant association with unfavorable outcome (hazard ratio, 1.10; 95% CI, 1.04-1.16; =0.001). Unfavorable outcome rates in low (≤5 points), intermediate (6-9), and high-risk (≥10) children at 3-year follow-up were 14.3%, 20.8%, and 38.5% respectively (<0.001). The updated score model showed good performance in predicting unfavorable outcome. Conclusions The echocardiographic score model for predicting RHD outcome was updated and validated for different latent RHD populations. It has potential utility in the clinical and screening setting for risk stratification of latent RHD.
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http://dx.doi.org/10.1161/JAHA.121.021622DOI Listing
September 2021

Deep neural network-estimated electrocardiographic age as a mortality predictor.

Nat Commun 2021 08 25;12(1):5117. Epub 2021 Aug 25.

Telehealth Center, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

The electrocardiogram (ECG) is the most commonly used exam for the evaluation of cardiovascular diseases. Here we propose that the age predicted by artificial intelligence (AI) from the raw ECG (ECG-age) can be a measure of cardiovascular health. A deep neural network is trained to predict a patient's age from the 12-lead ECG in the CODE study cohort (n = 1,558,415 patients). On a 15% hold-out split, patients with ECG-age more than 8 years greater than the chronological age have a higher mortality rate (hazard ratio (HR) 1.79, p < 0.001), whereas those with ECG-age more than 8 years smaller, have a lower mortality rate (HR 0.78, p < 0.001). Similar results are obtained in the external cohorts ELSA-Brasil (n = 14,236) and SaMi-Trop (n = 1,631). Moreover, even for apparent normal ECGs, the predicted ECG-age gap from the chronological age remains a statistically significant risk predictor. These results show that the AI-enabled analysis of the ECG can add prognostic information.
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http://dx.doi.org/10.1038/s41467-021-25351-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387361PMC
August 2021

The World Heart Federation Global Study on COVID-19 and Cardiovascular Disease.

Glob Heart 2021 04 19;16(1):22. Epub 2021 Apr 19.

Centre for Control of Chronic Conditions, Public Health Foundation India, World Heart Federation, London School of Hygiene & Tropical Medicine, UK.

Background: The emergence of novel coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase, and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions facilitated by international travel, leading to a pandemic. To guide effective control and interventions, primary data is required urgently, globally, including from low- and middle-income countries where documentation of cardiovascular manifestations and risk factors in people hospitalized with COVID-19 is limited.

Objectives: This study aims to describe the cardiovascular manifestations and cardiovascular risk factors in patients hospitalized with COVID-19.

Methods: We propose to conduct an observational cohort study involving 5000 patients recruited from hospitals in low-, middle- and high-income countries. Eligible adult COVID-19 patients will be recruited from the participating hospitals and followed-up until 30 days post admission. The outcomes will be reported at discharge and includes the need of ICU admission, need of ventilator, death (with cause), major adverse cardiovascular events, neurological outcomes, acute renal failure, and pulmonary outcomes.

Conclusion: Given the enormous burden posed by COVID-19 and the associated severe prognostic implication of CVD involvement, this study will provide useful insights on the risk factors for severe disease, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients particularly from low and middle income countries from where the data remain scant.
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http://dx.doi.org/10.5334/gh.950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064295PMC
April 2021

Deriving a parsimonious cardiac endpoint for use in epidemiological studies of Chagas disease: results from the Retrovirus Epidemiology Donor Study-II (REDS-II) cohort.

Rev Inst Med Trop Sao Paulo 2021 23;63:e31. Epub 2021 Apr 23.

Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, São Paulo, São Paulo, Brazil.

Chagas cardiomyopathy (ChCM) is a severe consequence of Trypanosoma cruzi infection and has a range of electrocardiographic (ECG) and echocardiographic (ECHO) manifestations. There is a need for a standard and parsimonious research cardiac end point that does not rely on expert panel adjudication, and it is not intended to change the ChCM definition. We use data from the REDS-II cohort to propose a simplified cardiac endpoint. A total of 499 T. cruzi-seropositive blood donors were included. All participants underwent a 12-lead ECG, echocardiogram and clinical examination, and those with abnormal findings were reviewed by a panel of cardiologists who classified cases as having Chagas cardiomyopathy or not. We created an exhaustive set of ECG and ECHO finding combinations and compared these with the panel's classification. We selected the simplest combination that most accurately reproduced the panel's results. Individual ECG and ECHO variables had low sensitivity for panel-defined cardiomyopathy. The best performing combination was right bundle branch block and/or ECHO evidence of left ventricular hypocontractility. This combination had 98% specificity and 85% sensitivity for panel-defined ChCM. It was not possible to improve the overall accuracy by addition of any other ECG or ECHO variable. Substituting right bundle branch block for the more inclusive finding of QRS interval > 120 ms produced similar results. The combination of prolonged QRS interval and/or left ventricular hypocontractility closely reproduced the REDS-II expert panel classification of Chagas ChCM. In conclusion, the simple and reproducible research endpoint proposed here captures most of the spectrum of cardiac abnormalities in Chagas disease.
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http://dx.doi.org/10.1590/S1678-9946202163031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075618PMC
May 2021

A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy.

Clin Infect Dis 2021 08;73(4):672-679

Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.

Background: Chagas disease is an infectious disease caused by the parasite Trypanosoma cruzi and is endemic from Latin American countries. The goal of our study was to identify novel genetic loci associated with chronic Chagas cardiomyopathy development in Chagas disease patients from different Latin American populations.

Methods: We performed a cross-sectional, nested case-control study including 3 sample collections from Colombia, Argentina, and Bolivia. Samples were genotyped to conduct a genome-wide association study (GWAS). These results were meta-analyzed with summary statistic data from Brazil, gathering a total of 3413 Chagas disease patients. To identify the functional impact of the associated variant and its proxies, we performed an in silico analysis of this region.

Results: The meta-analysis revealed a novel genome-wide statistically significant association with chronic Chagas cardiomyopathy development in rs2458298 (OR = 0.90, 95%CI = 0.87-0.94, P-value = 3.27 × 10-08), nearby the SAC3D1 gene. In addition, further in silico analyses displayed functional relationships between the associated variant and the SNX15, BAFT2, and FERMT3 genes, related to cardiovascular traits.

Conclusions: Our findings support the role of the host genetic factors in the susceptibility to the development of the chronic cardiac form of this neglected disease.
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http://dx.doi.org/10.1093/cid/ciab090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366831PMC
August 2021

Cytokine gene functional polymorphisms and phenotypic expression as predictors of evolution from latent to clinical rheumatic heart disease.

Cytokine 2021 02 19;138:155370. Epub 2020 Dec 19.

Laboratory of Cell-Cell Interactions, Institute of Biological Sciences, Department of Morphology, Belo Horizonte, Brazil; National Institute of Science and Technology in Tropical Diseases (INCT-DT), Salvador, BA, Brazil.

Introduction: Inflammation associated with rheumatic heart disease (RHD) is influenced by gene polymorphisms and inflammatory cytokines. There are currently no immunologic and genetic markers to discriminate latent versus clinical patients, critical to predict disease evolution. Employing machine-learning, we searched for predictors that could discriminate latent versus clinical RHD, and eventually identify latent patients that may progress to clinical disease.

Methods: A total of 212 individuals were included, 77 with latent, 100 with clinical RHD, and 35 healthy controls. Circulating levels of 27 soluble factors were evaluated using Bio-Plex ProTM® Human Cytokine Standard 27-plex assay. Gene polymorphism analyses were performed using RT-PCR for the following genes: IL2, IL4, IL6, IL10, IL17A, TNF and IL23.

Results: Serum levels of all cytokines were higher in clinical as compared to latent RHD patients, and in those groups than in controls. IL-4, IL-8, IL-1RA, IL-9, CCL5 and PDGF emerged in the final multivariate model as predictive factors for clinical, compared with latent RHD. IL-4, IL-8 and IL1RA had the greater power to predict clinical RHD. In univariate analysis, polymorphisms in IL2 and IL4 were associated with clinical RHD and in the logistic analysis, IL6 (GG + CG), IL10 (CT + TT), IL2 (CA + AA) and IL4 (CC) genotypes were associated with RHD.

Conclusion: Despite higher levels of all cytokines in clinical RHD patients, IL-4, IL-8 and IL-1RA were the best predictors of clinical disease. An association of polymorphisms in IL2, IL4, IL6 and IL10 genes and clinical RHD was observed. Gene polymorphism and phenotypic expression of IL-4 accurately discriminate latent versus clinical RHD, potentially instructing clinical management.
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http://dx.doi.org/10.1016/j.cyto.2020.155370DOI Listing
February 2021

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.

J Am Coll Cardiol 2020 12;76(25):2982-3021

University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, USA.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
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http://dx.doi.org/10.1016/j.jacc.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755038PMC
December 2020

COVID-19: Implications for People with Chagas Disease.

Glob Heart 2020 Oct 13;15(1):69. Epub 2020 Oct 13.

Drugs for Neglected Diseases initiative-Latin America, Rio de Janeiro, BR.

As the global COVID-19 pandemic advances, it increasingly impacts those vulnerable populations who already bear a heavy burden of neglected tropical disease. Chagas disease (CD), a neglected parasitic infection, is of particular concern because of its potential to cause cardiac, gastrointestinal, and other complications which could increase susceptibility to COVID-19. The over one million people worldwide with chronic Chagas cardiomyopathy require special consideration because of COVID-19's potential impact on the heart, yet the pandemic also affects treatment provision to people with acute or chronic indeterminate CD. In this document, a follow-up to the WHF-IASC Roadmap on CD, we assess the implications of coinfection with SARS-CoV-2 and , the etiological agent of CD. Based on the limited evidence available, we provide preliminary guidance for testing, treatment, and management of patients affected by both diseases, while highlighting emerging healthcare access challenges and future research needs.
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http://dx.doi.org/10.5334/gh.891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566506PMC
October 2020

Impact of a large-scale telemedicine network on emergency visits and hospital admissions during the coronavirus disease 2019 pandemic in Brazil: Data from the UNIMED-BH system.

J Telemed Telecare 2020 Oct 25:1357633X20969529. Epub 2020 Oct 25.

Serviço de Atendimento Móvel (GMOV), UNIMED-BH Cooperativa Médica, Brazil.

Introduction: Triage by on-demand telemedicine is a strategy for healthcare surge control in the COVID-19 pandemic. We aimed to assess the impact of a large-scale COVID-19 telemedicine system on emergency department (ED) visits and all-cause and cardiovascular hospital admissions in Brazil.

Methods: From March 18-May 18, 2020 we evaluated the database of a cooperative private health insurance, with 1.28 million clients. The COVID-19 telemedicine system consisted of: a) mobile app, which redirects to teleconsultations if indicated; b) telemonitoring system, with regular phone calls to suspected/confirmed COVID-19 cases to monitor progression; c) emergency ambulance system (EAS), with internet phone triage and counselling. ED visits and hospital admissions were recorded, with diagnoses assessed by the Diagnosis Related Groups method. COVID-19 diagnosis and deaths were identified from the patients' registries, and outcomes assessed until June 1st.

Results: In 60 days, 24,354 patients accessed one of the telemedicine systems. The most frequently utilized was telemonitoring (16,717, 69%), followed by teleconsultation (13,357, 55%) and EAS (687, 3%). The rates of ED and hospital admissions were: telemonitoring 19.7% (3,296) and 4.7% (782); teleconsultation 17.3% (2,313) and 2.4% (318) and EAS: 55.9% (384) and 56.5% (388) patients. At total 4.1% (1,010) had hospital admissions, 36% (363) with respiratory diseases (44 requiring mechanical ventilation) and 4.4% (44) with cardiovascular diagnoses. Overall, 277 (1.1%) patients had confirmed COVID-19 diagnosis, and 160 (0.7%) died, 9 with COVID-19.

Conclusion: Telemedicine resulted in low rates of ED visits and hospital admissions, suggesting positive impacts on healthcare utilization. Cardiovascular admissions were remarkably rare.
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http://dx.doi.org/10.1177/1357633X20969529DOI Listing
October 2020

The American Heart Association's Call to Action for Reducing the Global Burden of Rheumatic Heart Disease: A Policy Statement From the American Heart Association.

Circulation 2020 11 19;142(20):e358-e368. Epub 2020 Oct 19.

Rheumatic heart disease (RHD) affects ≈40 million people and claims nearly 300 000 lives each year. The historic passing of a World Health Assembly resolution on RHD in 2018 now mandates a coordinated global response. The American Heart Association is committed to serving as a global champion and leader in RHD care and prevention. Here, we pledge support in 5 key areas: (1) professional healthcare worker education and training, (2) technical support for the implementation of evidence-based strategies for rheumatic fever/RHD prevention, (3) access to essential medications and technologies, (4) research, and (5) advocacy to increase global awareness, resources, and capacity for RHD control. In bolstering the efforts of the American Heart Association to combat RHD, we hope to inspire others to collaborate, communicate, and contribute.
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http://dx.doi.org/10.1161/CIR.0000000000000922DOI Listing
November 2020

The GBD Brazil network: better information for health policy decision-making in Brazil.

Popul Health Metr 2020 09 30;18(Suppl 1):23. Epub 2020 Sep 30.

Hospital das Clínicas and School of Medicine, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 110, 1o andar, Belo Horizonte, MG, 30130-100, Brazil.

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http://dx.doi.org/10.1186/s12963-020-00224-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524595PMC
September 2020

Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study.

Cad Saude Publica 2020 09 2;36(8):e00072120. Epub 2020 Sep 2.

Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.

Homeostasis model assessment of insulin resistance (HOMA-IR) is a method to measure insulin resistance. HOMA-IR cut-offs for identifying metabolic syndrome might vary across populations and body mass index (BMI) levels. We aimed to investigate HOMA-insulin resistance cut-offs that best discriminate individuals with insulin resistance and with metabolic syndrome for each BMI category in a large sample of adults without diabetes in the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among the 12,313 participants with mean age of 51.2 (SD 8.9) years, the prevalence of metabolic syndrome was 34.6%, and 60.1% had overweight or obesity. The prevalence of metabolic syndrome among normal weight, overweight and obesity categories were, respectively, 13%, 43.2% and 60.7%. The point of maximum combined sensitivity and specificity of HOMA-IR to discriminate the metabolic syndrome was 2.35 in the whole sample, with increasing values at higher BMI categories. This investigation contributes to better understanding HOMA-IR values associated with insulin resistance and metabolic syndrome in a large Brazilian adult sample, and that use of cut-off points according to ROC curve may be the better strategy. It also suggests that different values might be appropriate across BMI categories.
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http://dx.doi.org/10.1590/0102-311X00072120DOI Listing
September 2020

WHF IASC Roadmap on Chagas Disease.

Glob Heart 2020 03 30;15(1):26. Epub 2020 Mar 30.

School of Medicine, CES University, Medellín, CO.

Background: Chagas Disease is a neglected tropical disease caused by the protozoan , with some of the most serious manifestations affecting the cardiovascular system. It is a chronic, stigmatizing condition, closely associated with poverty and affecting close to 6 million people globally. Although historically the disease was limited to endemic areas of Latin America recent years have seen an increasing global spread. In addition to the morbidity and mortality associated with the disease, the social and economic burdens on individuals and society are substantial. Often called the 'silent killer', Chagas disease is characterized by a long, asymptomatic phase in affected individuals. Approximately 30% then go on develop chronic Chagas cardiomyopathy and other serious cardiac complications such as stroke, rhythm disturbances and severe heart failure.

Methods: In a collaboration of the World Hearth Federation (WHF) and the Inter-American Society of Cardiology (IASC) a writing group consisting of 20 diverse experts on Chagas disease (CD) was convened. The group provided up to date expert knowledge based on their area of expertise. An extensive review of the literature describing obstacles to diagnosis and treatment of CD along with proposed solutions was conducted. A survey was sent to all WHF Members and, using snowball sampling to widen the consultation, to a variety of health care professionals working in the CD global health community. The results were analyzed, open comments were reviewed and consolidated, and the findings were incorporated into this document, thus ensuring a consensus representation.

Results: The WHF IASC Roadmap on Chagas Disease offers a comprehensive summary of current knowledge on prevention, diagnosis and management of the disease. In providing an analysis of 'roadblocks' in access to comprehensive care for Chagas disease patients, the document serves as a framework from which strategies for implementation such as national plans can be formulated. Several dimensions are considered in the analysis: healthcare system capabilities, governance, financing, community awareness and advocacy.

Conclusion: The WHF IASC Roadmap proposes strategies and evidence-based solutions for healthcare professionals, health authorities and governments to help overcome the barriers to comprehensive care for Chagas disease patients. This roadmap describes an ideal patient care pathway, and explores the roadblocks along the way, offering potential solutions based on available research and examples in practice. It represents a call to action to decision-makers and health care professionals to step up efforts to eradicate Chagas disease.
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http://dx.doi.org/10.5334/gh.484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218776PMC
March 2020

Cost-Effectiveness of Rheumatic Heart Disease Echocardiographic Screening in Brazil: Data from the PROVAR+ Study: Cost-effectiveness of RHD screening in Brazil.

Glob Heart 2020 02 20;15(1):18. Epub 2020 Feb 20.

Serviço de Cardiologia e Cirurgia Cardiovascular e Centro de Telessaúde, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, BR.

Introduction: In recent years, new technologies - noticeably ultra-portable echocardiographic machines - have emerged, allowing for Rheumatic Heart Disease (RHD) early diagnosis. We aimed to perform a cost-utility analysis to assess the cost-effectiveness of RHD screening with handheld devices in the Brazilian context.

Methods: A Markov model was created to assess the cost-effectiveness of one-time screening for RHD in a hypothetical cohort of 11-year-old socioeconomically disadvantaged children, comparing the intervention to standard care using a public perspective and a 30-year time horizon. The model consisted of 13 states: No RHD, Undiagnosed Asymptomatic Borderline RHD, Diagnosed Asymptomatic Borderline RHD, Untreated Asymptomatic Definite RHD, Treated Asymptomatic Definite RHD, Untreated Mild Clinical RHD, Treated Mild Clinical RHD, Untreated Severe Clinical RHD, Treated Severe Clinical RHD, Surgery, Post-Surgery and Death. The initial distribution of the population over the different states was derived from primary echo screening data. Costs of the different states were derived from the Brazilian public health system database. Transition probabilities and utilities were derived from published studies. A discount rate of 3%/year was used. A cost-effectiveness threshold of $25,949.85 per Disability Adjusted Life Year (DALY) averted is used in concordance with the 3x GDP per capita threshold in 2015.

Results: RHD echo screening is cost-effective with an Incremental Cost-Effectiveness Ratio of $10,148.38 per DALY averted. Probabilistic modelling shows that the intervention could be considered cost-effective in 70% of the iterations.

Conclusion: Screening for RHD with hand held echocardiographic machines in 11-year-old children in the target population is cost-effective in the Brazilian context.

Highlights: A cost-effectiveness analysis showed that Rheumatic Heart Disease (RHD) echocardiographic screening utilizing handheld devices, performed by non-physicians with remote interpretation by telemedicine is cost-effective in a 30-year time horizon in Brazil.The model included primary data from the first large-scale RHD screening program in Brazilian underserved populations and costs from the Unified Health System (SUS), and suggests that the Incremental Cost-Effectiveness Ratio of the intervention is considerably below the acceptable threshold for Brazil, even after a detailed sensitivity analysis.Considering the high prevalence of subclinical RHD in Brazil, and the significant economic burden posed by advanced disease, these data are important for the formulation of public policies and surveillance approaches.Cost-saving strategies first implemented in Brazil by the PROVAR study, such as task-shifting to non-physicians, computer-based training, routine use of affordable devices and telemedicine for remote diagnosis may help planning RHD control programs in endemic areas worldwide.
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http://dx.doi.org/10.5334/gh.529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218764PMC
February 2020

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

Nat Commun 2020 05 21;11(1):2542. Epub 2020 May 21.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
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http://dx.doi.org/10.1038/s41467-020-15706-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242331PMC
May 2020

Author Correction: Automatic diagnosis of the 12-lead ECG using a deep neural network.

Nat Commun 2020 05 1;11(1):2227. Epub 2020 May 1.

Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-16172-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195471PMC
May 2020

Automatic diagnosis of the 12-lead ECG using a deep neural network.

Nat Commun 2020 04 9;11(1):1760. Epub 2020 Apr 9.

Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. Deep Neural Networks (DNNs) are models composed of stacked transformations that learn tasks by examples. This technology has recently achieved striking success in a variety of task and there are great expectations on how it might improve clinical practice. Here we present a DNN model trained in a dataset with more than 2 million labeled exams analyzed by the Telehealth Network of Minas Gerais and collected under the scope of the CODE (Clinical Outcomes in Digital Electrocardiology) study. The DNN outperform cardiology resident medical doctors in recognizing 6 types of abnormalities in 12-lead ECG recordings, with F1 scores above 80% and specificity over 99%. These results indicate ECG analysis based on DNNs, previously studied in a single-lead setup, generalizes well to 12-lead exams, taking the technology closer to the standard clinical practice.
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http://dx.doi.org/10.1038/s41467-020-15432-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145824PMC
April 2020

Risk Score for Predicting 2-Year Mortality in Patients With Chagas Cardiomyopathy From Endemic Areas: SaMi-Trop Cohort Study.

J Am Heart Assoc 2020 03 11;9(6):e014176. Epub 2020 Mar 11.

Hospital das Clínicas and Faculdade de Medicina Universidade Federal de Minas Gerais Belo Horizonte Brazil.

Background Risk stratification of Chagas disease patients in the limited-resource setting would be helpful in crafting management strategies. We developed a score to predict 2-year mortality in patients with Chagas cardiomyopathy from remote endemic areas. Methods and Results This study enrolled 1551 patients with Chagas cardiomyopathy from Minas Gerais State, Brazil, from the SaMi-Trop cohort (The São Paulo-Minas Gerais Tropical Medicine Research Center). Clinical evaluation, ECG, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were performed. A Cox proportional hazards model was used to develop a prediction model based on the key predictors. The end point was all-cause mortality. The patients were classified into 3 risk categories at baseline (low, <2%; intermediate, ≥2% to 10%; high, ≥10%). External validation was performed by applying the score to an independent population with Chagas disease. After 2 years of follow-up, 110 patients died, with an overall mortality rate of 3.505 deaths per 100 person-years. Based on the nomogram, the independent predictors of mortality were assigned points: age (10 points per decade), New York Heart Association functional class higher than I (15 points), heart rate ≥80 beats/min (20 points), QRS duration ≥150 ms (15 points), and abnormal NT-proBNP adjusted by age (55 points). The observed mortality rates in the low-, intermediate-, and high-risk groups were 0%, 3.6%, and 32.7%, respectively, in the derivation cohort and 3.2%, 8.7%, and 19.1%, respectively, in the validation cohort. The discrimination of the score was good in the development cohort (C statistic: 0.82), and validation cohort (C statistic: 0.71). Conclusions In a large population of patients with Chagas cardiomyopathy, a combination of risk factors accurately predicted early mortality. This helpful simple score could be used in remote areas with limited technological resources.
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http://dx.doi.org/10.1161/JAHA.119.014176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335521PMC
March 2020

ELISA Saliva for Antibody Detection: An Alternative for Serological Surveys in Endemic Regions.

Am J Trop Med Hyg 2020 04;102(4):800-803

School of Medicine, University of São Paulo, São Paulo, Brazil.

Chagas is a neglected disease endemic in Latin America. Vector transmission control had been aggressively performed. Recent entomological surveillance in Brazil has revealed natural infection rates ranging from 0.40% to 0.52%. Although serological surveys are complex to develop, they are important for disease control. In this study, we validated the use of saliva in ELISA commercial kits with a cohort of 100 patients with Chagas disease followed at Hospital das Clinicas in São Paulo, Brazil, and 50 healthy controls. Five ELISA kits for detecting antibodies against were tested. The best discrimination between Chagas patients and controls was observed with the Wiener kit, which yielded a sensitivity of 97% and a specificity of 100%. Our findings reveal that the use of saliva may be an alternative to large-scale screening surveys in detecting antibodies; it is a noninvasive sample collection method potentially key to large-scale screening in children.
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http://dx.doi.org/10.4269/ajtmh.18-0330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124906PMC
April 2020

Atrial fibrillation detection with a portable device during cardiovascular screening in primary care.

Heart 2020 08 4;106(16):1261-1266. Epub 2020 Feb 4.

Serviço de Cardiologia e Cirurgia Cardiovascular e Centro de Telessaúde do Serviço de Cardiologia e Cirurgia Cardiovascular e Centro de Telessaúde do, Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Introduction: A novel handheld dual-electrode stick is a portable atrial fibrillation (AF) screening device (AFSD). We evaluated AFSD performance in primary care patients referred for echocardiogram (echo).

Methods: The AFSD has a light indication of irregular rhythm and single-lead ECG recording. Patients were instructed to hold the device for 1 min, and AF indication was recorded. A 12-lead ECG was performed for all AFSD-positive patients and 250 patients with negative AFSD screen. Echos were performed based on a clinical risk score: all high-risk patients and a sampling of low-risk patients underwent complete echo. Intermediate risk patients first had a screening echocardiogram, with a follow-up complete study if abnormality was suspected.

Results: In 5 days, 1518 patients underwent clinical evaluation and cardiovascular risk stratification: mean age 58±16 years, 66% women. The AFSD was positive in 6.4%: 12.6% high risk, 6.1% intermediate risk and 2.2% low risk. Older age was a risk factor (9.3% vs 4.8% in those more than and less than 65 years, p=0.001). AFSD positive was independently associated with heart disease in echo (OR=3.9, 95% CI 2.1 to 7.2, p<0.001). Compared with 12-lead ECG, the AFSD had sensitivity of 90.2% (95% CI 77.0% to 97.3%) and specificity of 84.0% (95% CI 79.3% to 88.0%) for AF detection.

Conclusion: AFSD demonstrated high sensitivity for AF detection in primary care patients referred for echo. AF prevalence was substantial and independently associated with structural or functional heart disease, suggesting that AFSD screening could be a useful primary care tool to stratify risk and prioritise echo.
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http://dx.doi.org/10.1136/heartjnl-2019-316277DOI Listing
August 2020

Relation of Thoracic Aortic and Coronary Artery Calcium to Cardiovascular Risk Factors (from The Brazilian Longitudinal Study of Adult Health [ELSA-Brazil]).

Am J Cardiol 2019 12 6;124(11):1655-1661. Epub 2019 Sep 6.

Department of Social and Preventive Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Thoracic aortic calcium (TAC) and coronary artery calcium (CAC) are associated with an increased risk of cardiovascular disease (CVD) and death. However, risk factors associated with arterial calcium may vary across vascular beds. We verified whether TAC is associated with the same risk factors as is CAC in adults without established CVD. Cross-sectional analysis including 2,433 participants (aged 38 to 78 years) of ELSA-Brasil cohort in Minas Gerais, Brazil. Nonenhanced ECG-gated multislice computed tomography were performed to detect calcium in the thoracic aorta and the coronaries (2015 to 2016). Multivariate logistic regression evaluated the associations of both TAC and CAC with CVD risk factors (smoking, body mass index, physical activity, alcohol intake, family history of CVD, low-density lipoprotein- and high-density lipoprotein-cholesterol, HbA1c, blood pressure, antidiabetic, antihypertensive, and lipid lowering medications). Overall prevalence of TAC and CAC were 69% and 43%, respectively. CAC prevalence was lower among women (31%) than men (56%) (Adjusted odds ratio [OR] 0.30; 0.24 to 0.38). After adjustments, black individuals were less likely to have any CAC as compared with whites (OR 0.63; 0.47 to 0.86). Neither sex, nor race/skin color were statistically associated with TAC. Use of antidiabetic medications remained associated with CAC (OR 1.80; 1.23 to 2.631.01), but not with TAC. All other risk factors, except education, alcohol, physical activity and HbA1c, persisted statistically associated with both TAC and CAC in the final analysis, with small differences in the magnitudes of the ORs. In conclusion, the only disagreements seen in the risk factors associated with CAC and TAC were sex, race/skin color, and use of antidiabetic medications.
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http://dx.doi.org/10.1016/j.amjcard.2019.08.029DOI Listing
December 2019

Tele-electrocardiography and bigdata: The CODE (Clinical Outcomes in Digital Electrocardiography) study.

J Electrocardiol 2019 Nov - Dec;57S:S75-S78. Epub 2019 Sep 7.

Institute of Health and Wellbeing, University of Glasgow, United Kingdom.

Digital electrocardiographs are now widely available and a large number of digital electrocardiograms (ECGs) have been recorded and stored. The present study describes the development and clinical applications of a large database of such digital ECGs, namely the CODE (Clinical Outcomes in Digital Electrocardiology) study. ECGs obtained by the Telehealth Network of Minas Gerais, Brazil, from 2010 to 17, were organized in a structured database. A hierarchical free-text machine learning algorithm recognized specific ECG diagnoses from cardiologist reports. The Glasgow ECG Analysis Program provided Minnesota Codes and automatic diagnostic statements. The presence of a specific ECG abnormality was considered when both automatic and medical diagnosis were concordant; cases of discordance were decided using heuristisc rules and manual review. The ECG database was linked to the national mortality information system using probabilistic linkage methods. From 2,470,424 ECGs, 1,773,689 patients were identified. After excluding the ECGs with technical problems and patients <16 years-old, 1,558,415 patients were studied. High performance measures were obtained using an end-to-end deep neural network trained to detect 6 types of ECG abnormalities, with F1 scores >80% and specificity >99% in an independent test dataset. We also evaluated the risk of mortality associated with the presence of atrial fibrillation (AF), which showed that AF was a strong predictor of cardiovascular mortality and mortality for all causes, with increased risk in women. In conclusion, a large database that comprises all ECGs performed by a large telehealth network can be useful for further developments in the field of digital electrocardiography, clinical cardiology and cardiovascular epidemiology.
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http://dx.doi.org/10.1016/j.jelectrocard.2019.09.008DOI Listing
May 2021

Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals.

J Am Coll Cardiol 2019 06;73(24):3118-3131

Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.

Background: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.

Objectives: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.

Methods: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.

Results: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.

Conclusions: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.
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http://dx.doi.org/10.1016/j.jacc.2019.03.519DOI Listing
June 2019

Racial differences in the association between early socioeconomic position, birth weight, and arterial stiffness in adults from ELSA-Brasil.

Ann Epidemiol 2019 06 28;34:45-51. Epub 2019 Mar 28.

Faculdade de Medicina & Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Purpose: We investigated the association between social and nutritional adversities in childhood and increased arterial stiffness in adulthood, according to race/skin color.

Methods: We used baseline data (2008-2010) from 13,365 adults (aged 34-75 years) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). Childhood social and nutritional adversities were assessed by maternal education and birth weight. Race/skin color was self-reported.

Results: The lower the maternal education, the higher the cfPWV in adulthood in Whites, Browns, and Blacks. This association was no longer significant after adjusting for the participant's education level in Whites, but it persisted after full adjustment among Browns (low vs. high maternal education: β = 0.18, 95% confidence interval: 0.01; 0.34) and Blacks (low vs. high maternal education: β = 0.44, 95% confidence interval: 0.18; 0.70). On the other hand, the association between low birth weight and higher cfPWV was found only among Whites.

Conclusions: Our findings regarding the association between maternal education and arterial stiffness are consistent with the disproportionate burden of cardiovascular disease-related morbidity and mortality in Blacks and Browns. The fact that the association between birth weight and arterial stiffness was only present in Whites may have reflected a survival bias.
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http://dx.doi.org/10.1016/j.annepidem.2019.03.007DOI Listing
June 2019

Sex-specific patterns in the association between salt intake and blood pressure: The ELSA-Brasil study.

J Clin Hypertens (Greenwich) 2019 04 12;21(4):502-509. Epub 2019 Mar 12.

Faculty of Medicine, Hospital Universitário, University of São Paulo, São Paulo, Brazil.

Blood pressure (BP) is a strong cardiovascular risk factor, predicting cardiovascular mortality in the general population. High salt consumption is a major contributor of increased BP and hypertension. However, there is a controversy on whether BP response to salt intake would be sex-specific. Thus, we aimed to verify the changes in BP according to different salt intake in men and women in a large sample of adults. The present analysis refers to 12 813 participants (from 35 to 64 years) with a validated 12-hour overnight urine collection in which salt intake was estimated. A set of questionnaires, clinical examination, and laboratory tests were carried out during a single visit to one of the six investigation centers involved. Salt intake was 12.9 ± 5.9 g/d in men and 9.3 ± 4.3 g/d in women. BP increases as salt intake increases, regardless of using BP-lowering medication. The slope of increase in BP elicited by salt intake was significantly higher in women than in men. Thus, the increase in BP by salt intake was stepper in women even after controlling for confounders, regardless of using BP-lowering medication or being hypertensive. In conclusion, salt intake is elevated in this large sample of Brazilian adults in which only a few participants are compliant with the recommendation. Also, women have a higher responsiveness of BP according to salt intake than men, and it is not associated with age, BP level, or the use of BP-lowering medication.
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http://dx.doi.org/10.1111/jch.13509DOI Listing
April 2019

Lack of evidence of seronegative infection in an endemic area of Chagas disease.

Rev Inst Med Trop Sao Paulo 2019 Feb 14;61:e11. Epub 2019 Feb 14.

Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, São Paulo, São Paulo, Brazil.

The diagnosis of Chagas disease is based on the detection of Trypanosoma cruzi (T. cruzi)-specific antibodies. Nonetheless, there is concern about the sensitivity of current serological assays due to reports of T. cruzi PCR positivity among seronegative individuals. The aim of this study was to evaluate if T. cruzi seronegative infections occur in endemic areas. We recruited 2,157 individuals that were identified as having Chagas disease in a public health system database of an endemic region in Brazil. All participants were interviewed and 2,091 had a sample collected for serological and PCR testing. From these, 149 (7.1%) had negative serological results. PCR was positive in 610 samples (31.4%) of the 1,942 seropositive samples but in none of the 149 samples from seronegative participants. True T. cruzi seronegative infections seem to be rare (95% CI 0-3.7) and should not be a concern for blood supply, which relies on antibody screening.
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http://dx.doi.org/10.1590/S1678-9946201961011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376933PMC
February 2019

Greater aortic stiffness is associated with renal dysfunction in participants of the ELSA-Brasil cohort with and without hypertension and diabetes.

PLoS One 2019 4;14(2):e0210522. Epub 2019 Feb 4.

Medical School & Clinical Hospital, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Background: Arterial stiffness has been associated with renal dysfunction and its progression, but the pathophysiological relation underlying this association has not been fully established, particularly among individuals without hypertension and diabetes. We investigated the cross-sectional associations between arterial stiffness and renal function in adults without cardiovascular disease, and whether this association remained among subjects without hypertension and diabetes.

Methods: All eligible participants from ELSA-Brasil (2008-2010), aged 35 to 74 years (N = 13,586) were included, of whom 7,979 were free from hypertension and diabetes. The response variables were: 1) low glomerular filtration rate (eGFR<60ml/min/1.73m2) estimated by CKD-EPI; 2) increased albumin/creatinine ratio (ACR ≥30mg/g); and 3) chronic kidney disease (CKD). Arterial stiffness was ascertained by the carotid-femoral pulse wave velocity (PWV). The covariates were sex, age, race/color, level of schooling, smoking, body mass index, total cholesterol/HDL-c glycated hemoglobin, diabetes, systolic blood pressure, heart rate and use of antihypertensive drugs. Logistic regression was used to examine the associations.

Results: After all adjustments, 1 m/s increase in PWV was associated with ORs equal to 1.10 (95%CI: 1.04-1.16), 1.10 (95%CI: 1.05-1.16) and 1.12 (95%CI: 1.08-1.17) of low eGFR, high ACR, and CKD, respectively. In subjects without hypertension and diabetes, these ORs were 1.19 (95%CI: 1.07-1.33), 1.20 (95%CI: 1.07-1.32) and 1.21 (95%CI: 1.11-1.30), respectively.

Conclusion: The increase in PWV was associated with all renal dysfunction markers, even in individuals without hypertension and diabetes, suggesting a relation that is not completely mediated by the presence of these conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210522PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361418PMC
October 2019
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