Epidemiology of cardiometabolic health in Latin America and strategies to address disparities.

In Latin America and the Caribbean (LAC), sociodemographic context, socioeconomic disparities and the high level of urbanization provide a unique entry point to reflect on the burden of cardiometabolic disease in the region. Cardiovascular diseases are the main cause of death in LAC, precipitated by population growth and ageing together with a rapid increase in the prevalence of cardiometabolic risk factors, predominantly obesity and diabetes mellitus, over the past four decades. Strategies to address this growing cardiometabolic burden include both population-wide and individual-based initiatives tailored to the specific challenges faced by different LAC countries, which are heterogeneous. The implementation of public policies to reduce smoking and health system approaches to control hypertension are examples of scalable strategies. The challenges faced by LAC are also opportunities to foster innovative approaches to combat the high burden of cardiometabolic diseases such as implementing digital health interventions and team-based initiatives. This Review provides a summary of trends in the epidemiology of cardiometabolic diseases and their risk factors in LAC as well as context-specific disease determinants and potential solutions to improve cardiometabolic health in the region.

Outcomes of latent rheumatic heart disease: External validation of a simplified score in patients with and without secondary prophylaxis.

BACKGROUND: Secondary antibiotic prophylaxis reduces progression of latent rheumatic heart disease (RHD) but not all children benefit. Improved risk stratification could refine recommendations following positive screening. We aimed to evaluate the performance of a previously developed echocardiographic risk score to predict mid-term outcomes among children with latent RHD. METHODS: We included children who completed the GOAL, a randomized trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. Outcomes were determined by a 4-member adjudication panel. We applied the point-based score, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3 points), MV regurgitation jet length ≥ 2 cm (6 points), aortic valve focal thickening (4 points) and any aortic regurgitation (5 points)), to panel results. Unfavorable outcome was defined as progression of diagnostic category (borderline to definite, mild definite to moderate/severe definite), worsening valve involvement or remaining with mild definite RHD. RESULTS: 799 patients (625 borderline and 174 definite RHD) were included, with median follow-up of 24 months. At total 116 patients (14.5%) had unfavorable outcome per study criteria, 57.8% not under prophylaxis. The score was strongly associated with unfavorable outcome (HR = 1.26, 95% CI 1.16-1.37, p < 0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7-9 points) and high-risk (≥10 points) children at follow-up were 11.8%, 30.4%, and 42.2%, (p < 0.001) respectively (C-statistic = 0.64 (95% CI 0.59-0.69)). CONCLUSIONS: The simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes.

Combinação de Ferramentas de Telecardiologia para Estratificação de Risco Cardiovascular na Atenção Primária: Dados do Estudo PROVAR+ / Combination of Tele-Cardiology Tools for Cardiovascular Risk Stratification in Primary Care: Data from the PROVAR+ Study

Resumo Fundamento: As ferramentas de telecardiologia são estratégias valiosas para melhorar a estratificação de risco. Objetivo: Objetivamos avaliar a acurácia da tele-eletrocardiografia (ECG) para predizer anormalidades no ecocardiograma de rastreamento na atenção primária. Métodos: Em 17 meses, 6 profissionais de saúde em 16 unidades de atenção primária foram treinados em protocolos simplificados de ecocardiografia portátil. Tele-ECGs foram registrados para diagnóstico final por um cardiologista. Pacientes consentidos com anormalidades maiores no ECG pelo código de Minnesota e uma amostra 1:5 de indivíduos normais foram submetidos a um questionário clínico e ecocardiograma de rastreamento interpretado remotamente. A doença cardíaca grave foi definida como doença valvular moderada/grave, disfunção/hipertrofia ventricular, derrame pericárdico ou anormalidade da motilidade. A associação entre alterações maiores do ECG e anormalidades ecocardiográficas foi avaliada por regressão logística da seguinte forma: 1) modelo não ajustado; 2) modelo 1 ajustado por idade/sexo; 3) modelo 2 mais fatores de risco (hipertensão/diabetes); 4) modelo 3 mais história de doença cardiovascular (Chagas/cardiopatia reumática/cardiopatia isquêmica/AVC/insuficiência cardíaca). Foram considerados significativos valores de p < 0,05. Resultados: No total, 1.411 pacientes realizaram ecocardiograma, sendo 1.149 (81%) com anormalidades maiores no ECG. A idade mediana foi de 67 anos (intervalo interquartil de 60 a 74) e 51,4% eram do sexo masculino. As anormalidades maiores no ECG se associaram a uma chance 2,4 vezes maior de doença cardíaca grave no ecocardiograma de rastreamento na análise bivariada (OR = 2,42 [IC 95% 1,76 a 3,39]) e permaneceram significativas (p < 0,001) após ajustes no modelo 2 (OR = 2,57 [IC 95% 1,84 a 3,65]), modelo 3 (OR = 2,52 [IC 95% 1,80 a 3,58]) e modelo 4 (OR = 2,23 [IC 95% 1,59 a 3,19]). Idade, sexo masculino, insuficiência cardíaca e doença cardíaca isquêmica também foram preditores independentes de doença cardíaca grave no ecocardiograma. Conclusões: As anormalidades do tele-ECG aumentaram a probabilidade de doença cardíaca grave no ecocardiograma de rastreamento, mesmo após ajustes para variáveis demográficas e clínicas.

Abstract Background: Tele-cardiology tools are valuable strategies to improve risk stratification. Objective: We aimed to evaluate the accuracy of tele-electrocardiography (ECG) to predict abnormalities in screening echocardiography (echo) in primary care (PC). Methods: In 17 months, 6 health providers at 16 PC units were trained on simplified handheld echo protocols. Tele-ECGs were recorded for final diagnosis by a cardiologist. Consented patients with major ECG abnormalities by the Minnesota code, and a 1:5 sample of normal individuals underwent clinical questionnaire and screening echo interpreted remotely. Major heart disease was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion, or wall-motion abnormalities. Association between major ECG and echo abnormalities was assessed by logistic regression as follows: 1) unadjusted model; 2) model 1 adjusted for age/sex; 3) model 2 plus risk factors (hypertension/diabetes); 4) model 3 plus history of cardiovascular disease (Chagas/rheumatic heart disease/ischemic heart disease/stroke/heart failure). P-values < 0.05 were considered significant. Results: A total 1,411 patients underwent echo; 1,149 (81%) had major ECG abnormalities. Median age was 67 (IQR 60 to 74) years, and 51.4% were male. Major ECG abnormalities were associated with a 2.4-fold chance of major heart disease on echo in bivariate analysis (OR = 2.42 [95% CI 1.76 to 3.39]), and remained significant after adjustments in models (p < 0.001) 2 (OR = 2.57 [95% CI 1.84 to 3.65]), model 3 (OR = 2.52 [95% CI 1.80 to3.58]), and model 4 (OR = 2.23 [95%CI 1.59 to 3.19]). Age, male sex, heart failure, and ischemic heart disease were also independent predictors of major heart disease on echo. Conclusions: Tele-ECG abnormalities increased the likelihood of major heart disease on screening echo, even after adjustments for demographic and clinical variables.

Volume de Gordura Epicárdica está Associada com Disfunção Endotelial, mas Não com Calcificação Coronariana: Do ELSA-Brasil / Epicardial Fat Volume Is Associated with Endothelial Dysfunction, but not with Coronary Calcification: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Resumo Fundamento O aumento no volume de gordura epicárdica (VGE) está relacionado com doença arterial coronariana (DAC), independentemente de gordura visceral ou subcutânea. O mecanismo dessa associação não é claro. O escore de cálcio coronariano (CC) e a disfunção endotelial estão relacionados com eventos coronarianos, mas não está bem esclarecido se o VGE está relacionado com esses marcadores. Objetivos Avaliar a associação entre VGE medido por método automatizado, fatores de risco cardiovasculares, escore de CC, e função endotelial. Métodos: Em 470 participantes do Estudo Longitudinal de Saúde do Adulto LSA-Brasil com medidas de VGE, escore de CC e função endotelial, realizamos modelos multivariados para avaliar a relação entre fatore de risco cardiovascular e VGE (variável resposta), e entre VGE (variável explicativa), e função endotelial ou escore de CC. Valor de p<0,05 bilateral foi considerado estatisticamente significativo. Resultados A idade média foi 55 ± 8 anos, e 52,3% dos pacientes eram homens. O VGE médio foi 111mL (86-144), e a prevalência de escore de CC igual a zero foi 55%. Nas análises multivariadas, um VGE mais alto relacionou-se com sexo feminino, idade mais avançada, circunferência da cintura, e triglicerídeos (p<0,001 para todos). Um VGE mais alto foi associado com pior função endotelial: em comparação ao primeiro quartil, os valores de odds ratio para a amplitude de pulso basal foram (q2=1,22; IC95% 1,07-1,40; q3=1,50, IC95% 1,30-1,74; q4=1,50, IC95% 1,28-1,79) e para a razão de tonometria arterial periférica foram (q2=0,87; IC95% 0,81-0,95; q3=0,86, IC95% 0,79-0,94; q4=0,80, IC95% 0,73-0,89), mas não com escore de CC maior que zero. Conclusão Um VGE mais alto associou-se com comprometimento da função endotelial, mas não com escore de CC. Os resultados sugerem que o VGE esteja relacionado ao desenvolvimento de DAC por uma via diferente da via do CC, possivelmente pela piora da disfunção endotelial e doença microvascular.

Abstract Background The increase in epicardial fat volume (EFV) is related to coronary artery disease (CAD), independent of visceral or subcutaneous fat. The mechanism underlying this association is unclear. Coronary artery calcium (CAC) score and endothelial dysfunction are related to coronary events, but whether EFV is related to these markers needs further clarification. Objectives To evaluate the association between automatically measured EFV, cardiovascular risk factors, CAC, and endothelial function. Methods In 470 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) with measures of EFV, CAC score and endothelial function, we performed multivariable models to evaluate the relation between cardiovascular risk factors and EFV (response variable), and between EFV (explanatory variable) and endothelial function variables or CAC score. Two-sided p <0.05 was considered statistically significant. Results Mean age was 55 ± 8 years, 52.3% of patients were men. Mean EFV was 111mL (IQ 86-144), and the prevalence of CAC score=0 was 55%. In the multivariable analyses, increased EFV was related to female sex, older age, waist circumference, and triglycerides (p<0.001 for all). Higher EFV was associated with worse endothelial function: as compared with the first quartile, the odds ratio for basal pulse amplitude were (q2=1.22, 95%CI 1.07-1.40; q3=1.50, 95%CI 1.30-1.74; q4=1.50, 95%CI 1.28-1.79) and for peripheral arterial tonometry ratio were (q2=0.87, 95%CI 0.81-0.95; q3=0.86, 95%CI 0.79-0.94; q4=0.80, 95%CI 0.73-0.89), but not with CAC score>0. Conclusion Higher EFV was associated with impaired endothelial function, but not with CAC. The results suggest that EFV is related to the development of CAD through a pathway different from the CAC pathway, possibly through aggravation of endothelial dysfunction and microvascular disease.

Avaliação do Impacto da Implantação de um Sistema de Ambulância Pré-Hospitalar sobre Mortalidade por Infarto Agudo do Miocárdio em um País em Desenvolvimento / Assessment of the Impact of the Implementation of a Pre-Hospital Ambulance System on Acute Myocardial Infarction Mortality in a Developing Country

Resumo Fundamento O manejo efetivo de pacientes com infarto agudo do miocárdio (IAM) é tempo-dependente. Objetivos Avaliar os impactos da implantação do atendimento pré-hospitalar nas taxas de internação e de mortalidade associadas ao IAM. Métodos Estudo retrospectivo e ecológico, que avaliou dados do Sistema Único de Saúde, de todos os 853 municípios de Minas Gerais, de 2008 a 2016. A assimetria excessiva da mortalidade geral e intra-hospitalar por IAM foi suavizada usando o método empírico de Bayes. Este estudo avaliou a relação entre o do Serviço de Atendimento Médico de Urgência (SAMU) em cada município e os seguintes 3 desfechos: taxa de mortalidade geral por IAM, taxa de mortalidade intra-hospitalar por IAM e taxa de internação por IAM, utilizando o modelo hierárquico de Poisson. As taxas foram corrigidas pela estrutura etária e destendenciadas pela sazonalidade e influências temporais. Foi adotado um intervalo de confiança de 95%. Resultados As taxas de mortalidade por IAM diminuíram ao longo do estudo, em média 2% por ano, com variação sazonal. A mortalidade intra-hospitalar também apresentou tendência de queda, de 13,81% em 2008 para 11,43% em 2016. A implantação do SAMU foi associada à diminuição da mortalidade por IAM ( odds ratio [OR] = 0,967, IC 95% 0,936 a 0,998) e mortalidade intra-hospitalar por IAM (OR = 0,914, IC 95% 0,845 a 0,986), sem associação significativa com internações (OR 1,003, IC 95% 0,927 a 1,083). Conclusão A implantação do SAMU esteve associada a uma redução modesta, mas significativa, na mortalidade intra-hospitalar. Esse achado reforça o papel fundamental do cuidado pré-hospitalar no cuidado do IAM e a necessidade de investimentos nesse serviço para melhorar os desfechos clínicos em países de baixa e média renda.

Abstract Background The effective management of patients with acute myocardial infarction (AMI) is time-dependent. Objectives To assess the impacts of the implementation of prehospital care on admission rates and mortality associated with AMI. Methods Retrospective, ecological study, which assessed data from the Brazilian Universal Health System, from all 853 municipalities of Minas Gerais, from 2008 to 2016. Excessive skewness of general and in-hospital mortality rates was smoothed using the empirical Bayes method. This study assessed the relationship between Mobile Emergency Care Service (SAMU) in each municipality and the following 3 outcomes: mortality rate due to AMI, AMI in-hospital mortality, and AMI hospitalization rate, using the Poisson hierarchical model. Rates were corrected by age structure and detrended by seasonality and temporal influences. A confidence interval of 95% was adopted. Results AMI mortality rates decreased throughout the study, on average 2% per year, with seasonal variation. AMI in-hospital mortality also showed a decreasing trend, from 13.81% in 2008 to 11.43% in 2016. SAMU implementation was associated with decreased AMI mortality (odds ratio [OR] = 0.967, 95% confidence interval [CI] 0.936 to 0.998) and AMI in-hospital mortality (OR = 0.914, 95% CI 0.845 to 0.986), with no relation with hospitalizations (OR = 1.003, 95% CI 0.927 to 1.083). Conclusion SAMU implementation was associated with a modest but significant decrease in AMI in-hospital mortality. This finding reinforces the key role of prehospital care in AMI care and the need for investments on this service to improve clinical outcomes in low- and middle-income countries.

Epicardial Fat Volume Is Associated with Endothelial Dysfunction, but not with Coronary Calcification: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). / Volume de Gordura Epicárdica está Associada com Disfunção Endotelial, mas Não com Calcificação Coronariana: Do ELSA-Brasil.

BACKGROUND: The increase in epicardial fat volume (EFV) is related to coronary artery disease (CAD), independent of visceral or subcutaneous fat. The mechanism underlying this association is unclear. Coronary artery calcium (CAC) score and endothelial dysfunction are related to coronary events, but whether EFV is related to these markers needs further clarification. OBJECTIVES: To evaluate the association between automatically measured EFV, cardiovascular risk factors, CAC, and endothelial function. METHODS: In 470 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) with measures of EFV, CAC score and endothelial function, we performed multivariable models to evaluate the relation between cardiovascular risk factors and EFV (response variable), and between EFV (explanatory variable) and endothelial function variables or CAC score. Two-sided p <0.05 was considered statistically significant. RESULTS: Mean age was 55 ± 8 years, 52.3% of patients were men. Mean EFV was 111mL (IQ 86-144), and the prevalence of CAC score=0 was 55%. In the multivariable analyses, increased EFV was related to female sex, older age, waist circumference, and triglycerides (p<0.001 for all). Higher EFV was associated with worse endothelial function: as compared with the first quartile, the odds ratio for basal pulse amplitude were (q2=1.22, 95%CI 1.07-1.40; q3=1.50, 95%CI 1.30-1.74; q4=1.50, 95%CI 1.28-1.79) and for peripheral arterial tonometry ratio were (q2=0.87, 95%CI 0.81-0.95; q3=0.86, 95%CI 0.79-0.94; q4=0.80, 95%CI 0.73-0.89), but not with CAC score>0. CONCLUSION: Higher EFV was associated with impaired endothelial function, but not with CAC. The results suggest that EFV is related to the development of CAD through a pathway different from the CAC pathway, possibly through aggravation of endothelial dysfunction and microvascular disease.

FUNDAMENTO: O aumento no volume de gordura epicárdica (VGE) está relacionado com doença arterial coronariana (DAC), independentemente de gordura visceral ou subcutânea. O mecanismo dessa associação não é claro. O escore de cálcio coronariano (CC) e a disfunção endotelial estão relacionados com eventos coronarianos, mas não está bem esclarecido se o VGE está relacionado com esses marcadores. OBJETIVOS: Avaliar a associação entre VGE medido por método automatizado, fatores de risco cardiovasculares, escore de CC, e função endotelial. Métodos: Em 470 participantes do Estudo Longitudinal de Saúde do Adulto LSA-Brasil com medidas de VGE, escore de CC e função endotelial, realizamos modelos multivariados para avaliar a relação entre fatore de risco cardiovascular e VGE (variável resposta), e entre VGE (variável explicativa), e função endotelial ou escore de CC. Valor de p<0,05 bilateral foi considerado estatisticamente significativo. RESULTADOS: A idade média foi 55 ± 8 anos, e 52,3% dos pacientes eram homens. O VGE médio foi 111mL (86-144), e a prevalência de escore de CC igual a zero foi 55%. Nas análises multivariadas, um VGE mais alto relacionou-se com sexo feminino, idade mais avançada, circunferência da cintura, e triglicerídeos (p<0,001 para todos). Um VGE mais alto foi associado com pior função endotelial: em comparação ao primeiro quartil, os valores de odds ratio para a amplitude de pulso basal foram (q2=1,22; IC95% 1,07-1,40; q3=1,50, IC95% 1,30-1,74; q4=1,50, IC95% 1,28-1,79) e para a razão de tonometria arterial periférica foram (q2=0,87; IC95% 0,81-0,95; q3=0,86, IC95% 0,79-0,94; q4=0,80, IC95% 0,73-0,89), mas não com escore de CC maior que zero. CONCLUSÃO: Um VGE mais alto associou-se com comprometimento da função endotelial, mas não com escore de CC. Os resultados sugerem que o VGE esteja relacionado ao desenvolvimento de DAC por uma via diferente da via do CC, possivelmente pela piora da disfunção endotelial e doença microvascular.

All-cause and cause-specific mortality among people with severe mental illness in Brazil's public health system, 2000-15: a retrospective study.

BACKGROUND: People with severe mental illness have a mortality rate higher than the general population, living an average of 10-20 years less. Most studies of mortality among people with severe mental illness have occurred in high-income countries (HICs). We aimed to estimate all-cause and cause-specific relative risk (RR) and excess mortality rate (EMR) in a nationwide cohort of inpatients with severe mental illness compared with inpatients without severe mental illness in a middle income country, Brazil. METHODS: This national retrospective cohort study included all patients hospitalised through the Brazilian Public Health System (Sistema Único de Saúde [SUS]-Brazil) between Jan 1, 2000, and April 21, 2015. Probabilistic and deterministic record linkages integrated data from the Hospital Information System (Sistema de informações Hospitalares) and the National Mortality System (Sistema de Informação sobre Mortalidade). Follow-up duration was measured from the date of the patients' first hospitalisation until their death, or until April 21, 2015. Severe mental illness was defined as schizophrenia, bipolar disorder, or depressive disorder by ICD-10 codes used for the admission. RR and EMR were calculated with 95% CIs, comparing mortality among patients with severe mental illness with those with other diagnoses for patients aged 15 years and older. We redistributed deaths using the Global Burden of Diseases, Injuries, and Risk Factors Study methodology if ill-defined causes of death were stated as an underlying cause. FINDINGS: From Jan 1, 2000, to April 21, 2015, 72 021 918 patients (31 510 035 [43·8%] recorded as male and 40 974 426 [56·9%] recorded as female; mean age 41·1 (SD 23·8) years) were admitted to hospital, with 749 720 patients (372 458 [49·7%] recorded as male and 378 670 [50·5%] as female) with severe mental illness. 5 102 055 patient deaths (2 862 383 [56·1%] recorded as male and 2 314 781 [45·4%] as female) and 67 485 deaths in patients with severe mental illness (39 099 [57·9%] recorded as male and 28 534 [42·3%] as female) were registered. The RR for all-cause mortality in patients with severe mental illness was 1·27 (95% CI 1·27-1·28) and the EMR was 2·52 (2·44-2·61) compared with non-psychiatric inpatients during the follow-up period. The all-cause RR was higher for females and for younger age groups; however, EMR was higher in those aged 30-59 years. The RR and EMR varied across the leading causes of death, sex, and age groups. We identified injuries (suicide, interpersonal violence, and road injuries) and cardiovascular disease (ischaemic heart disease) as having the highest EMR among those with severe mental illness. Data on ethnicity were not available. INTERPRETATION: In contrast to studies from HICs, inpatients with severe mental illness in Brazil had high RR for idiopathic epilepsy, tuberculosis, HIV, and acute hepatitis, and no significant difference in mortality from cancer compared with inpatients without severe mental illness. These identified causes should be addressed as a priority to maximise mortality prevention among people with severe mental illness, especially in a middle-income country like Brazil that has low investment in mental health. FUNDING: Bill and Melinda Gates Foundation, Fundação de Amparo a Pesquisa do Estado de Minas Gerais, FAPEMIG, and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil.

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

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.

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

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.

Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study / Modelo de avaliação da homeostase de resistência à insulina (HOMA-IR) e síndrome metabólica na linha de base de uma coorte brasileira multicêntrica: estudo ELSA-Brasil / Modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) y síndrome metabólico en la línea de base de una cohorte brasileña multicéntrica: estudio ELSA-Brasil

Abstract: 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.

Resumo: O modelo de avaliação da homeostase da resistência à insulina (HOMA-IR) é um método para medir a resistência à insulina. Os pontos de corte do HOMA-IR para identificar a síndrome metabólica podem variar entre as populações e os níveis de índice de massa corporal (IMC). Nosso objetivo foi investigar os pontos de corte do HOMA-IR que melhor discriminam indivíduos com resistência à insulina e com síndrome metabólica para cada categoria de IMC em uma grande amostra de adultos sem diabetes na linha de base do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Entre os 12.313 participantes com média de idade de 51,2 (DP 8,9) anos, a prevalência de síndrome metabólica foi de 34,6%, e 60,1% apresentavam sobrepeso ou obesidade. As prevalências de síndrome metabólica nas categorias de peso normal, sobrepeso e obesidade foram, respectivamente, 13%, 43,2% e 60,7%. O ponto de máxima sensibilidade e especificidade combinadas do HOMA-IR para discriminar a síndrome metabólica foi de 2,35 em toda a amostra, com valores crescentes nas categorias de IMC mais elevadas. Esta investigação contribui para o melhor entendimento dos valores de HOMA-IR associados à resistência à insulina e síndrome metabólica em uma grande amostra de adultos brasileiros, e que o uso de pontos de corte de acordo com a curva ROC pode ser a melhor estratégia. Também sugere que valores diferentes podem ser apropriados nas categorias de IMC.

Resumen: El modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) es un método para medir la resistencia a la insulina. Los cortes HOMA-IR para identificar el síndrome metabólico pueden variar entre las poblaciones y los niveles del índice de masa corporal (IMC). El objetivo fue investigar los cortes de HOMA-IR que mejor discriminaban individuos con resistencia a la insulina y con síndrome metabólico para cada categoría de IMC, en una extensa muestra de adultos sin diabetes en la base de referencia del Estudio Longitudinal de Salud del Adulto (ELSA-Brasil). Entre los 12.313 participantes con una media de edad de 51,2 años (DE 8,9), la prevalencia de síndrome metabólico fue 34,6%, y un 60,1% sufría sobrepeso u obesidad. La prevalencia de síndrome metabólico entre las categorías: peso normal, sobrepeso y obesidad fueron respectivamente, 13%, 43,2% y 60,7%. El punto de máxima sensibilidad combinada y especificidad de HOMA-IR para discriminar el síndrome metabólico fue 2,35 en toda la muestra, con valores crecientes en las categorías de IMC más altas. Esta investigación contribuye a entender mejor los valores HOMA-IR, asociados con resistencia a la insulina y síndrome metabólico en una gran muestra de adultos brasileños, además del planteamiento de que el uso de puntos de corte según la curva ROC es quizás la mejor estrategia a seguir. También sugiere que valores diferentes pueden ser apropiados a través de las categorías de IMC.

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

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.

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

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.

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

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.

Simplified Echocardiography Screening Criteria for Diagnosing and Predicting Progression of Latent Rheumatic Heart Disease.

BACKGROUND: The 2012 World Heart Federation Criteria are the current gold standard for the diagnosis of latent rheumatic heart disease (RHD). Because data and experience using these criteria have grown, there is opportunity to simplify and develop outcome prediction tools. We aimed to develop a simple echocardiographic score applicable for RHD screening with potential to predict disease progression. METHODS: This study included 3 cohorts used for score derivation (n=9501), score validation (n=7312), and assessment of outcomes prediction (n=227). In the derivation cohort, variables independently associated with definite RHD were assigned point values proportional to their regression coefficients. The sum of these values was stratified into low (0-6), intermediate (7-9), and high (≥10) risk. RESULTS: Five components were selected for score development, including mitral valve anterior leaflet thickening, excessive leaflet tip motion, and regurgitation jet length ≥2 cm, and aortic valve focal thickening and any regurgitation. The score showed optimal discrimination and calibration for RHD diagnosis in the derivation and validation cohorts (C statistic, 0.998 and 0.994, respectively), with good discrimination for predicting disease progression (C statistic, 0.811). Progression-free survival rate in the low-risk children at 1-, 2-, and 3-year follow-up was 100%, 100%, and 93%, respectively, compared with 90%, 60%, and 47% in high-risk group. The point-based score was strongly associated with disease progression (hazard ratio, 1.270; 95% CI, 1.188-1.358; P<0.001). CONCLUSIONS: This simplified score, based on components of the World Heart Federation criteria, is highly accurate to recognize definite RHD and provides the first tool for risk stratification, assigning children with latent RHD to low, intermediate, or high risk based on echocardiographic features at diagnosis.

Integration of echocardiographic screening by non-physicians with remote reading in primary care.

INTRODUCTION: Heart disease (HD) accounts for high morbidity and mortality in Brazil. Underserved populations often suffer long delays in diagnosis. We aimed to evaluate the feasibility of integrating screening echocardiography (echo) with remote interpretation in the established primary care system (PC) in Brazil and to assess HD prevalence. METHODS: Over 11 months, 20 healthcare workers (four physicians, four nurses, and 12 technicians) at 16 PC centres were trained on simplified handheld echo protocols. Three screening (SC) groups, including all consented patients aged 17-20, 35-40 and 60-65 years, and patients referred (RF) for clinical indications underwent focused echo. Studies were remotely interpreted through telemedicine. Significant HD was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion, wall-motion abnormalities and congenital heart disease. RESULTS: Total 1004 patients underwent echo; 299 (29.8%) in the SC group. Median age was 51±18 years, 63.9% females; 42.7% had cardiovascular symptoms. Significant HD was found in 354 (35.3%) patients (23.4% in SC vs 40.3% in RF group, p<0.001). Prevalence was higher in patients in the SC group aged >60 years (29.2%), compared with 35-40 (14.9%) and under 20 (16.5%), p=0.012. Comparing SC to RF groups, moderate/severe left ventricular dysfunction was observed in 4.1% vs 8.1%, p=0.03, mitral regurgitation in 8.9% vs 20.3%, p<0.001 and aortic stenosis in 5.4% vs 4.3%, p=0.51. CONCLUSIONS: Integration focused echo into PC is feasible in Brazil as a strategy to deliver cardiovascular care to low-resourced areas through task shifting. The burden of HD observed suggests this tool may improve early diagnosis and referral.

Cardiovascular Disease Epidemiology in Portuguese-Speaking Countries: data from the Global Burden of Disease, 1990 to 2016 / Epidemiologia das Doenças Cardiovasculares em Países de Língua Portuguesa: Dados do "Global Burden of Disease", 1990 a 2016

Abstract Background: Portuguese-speaking countries (PSC) share the influence of the Portuguese culture but have socioeconomic development patterns that differ from that of Portugal. Objective: To describe trends in cardiovascular disease (CVD) morbidity and mortality in the PSC between 1990 and 2016, stratified by sex, and their association with the respective sociodemographic indexes (SDI). Methods: This study used the Global Burden of Disease (GBD) 2016 data and methodology. Data collection followed international standards for death certification, through information systems on vital statistics and mortality surveillance, surveys, and hospital registries. Techniques were used to standardize causes of death by the direct method, as were corrections for underreporting of deaths and garbage codes. To determine the number of deaths due to each cause, the CODEm (Cause of Death Ensemble Model) algorithm was applied. Disability-adjusted life years (DALYs) and SDI (income per capita, educational attainment and total fertility rate) were estimated for each country. A p-value <0.05 was considered significant. Results: There are large differences, mainly related to socioeconomic conditions, in the relative impact of CVD burden in PSC. Among CVD, ischemic heart disease was the leading cause of death in all PSC in 2016, except for Mozambique and Sao Tome and Principe, where cerebrovascular diseases have supplanted it. The most relevant attributable risk factors for CVD among all PSC are hypertension and dietary factors. Conclusion: Collaboration among PSC may allow successful experiences in combating CVD to be shared between those countries.

Resumo Fundamento: Os países de língua portuguesa (PLP) partilham a influência da cultura portuguesa com desenvolvimento socioeconômico diverso de Portugal. Objetivo: Descrever as tendências de morbidade e mortalidade por doenças cardiovasculares (DCV) nos PLP, entre 1990 e 2016, estratificadas por sexo, e sua associação com os respectivos índices sociodemográficos (SDI). Métodos: O estudo utilizou dados e metodologia do Global Burden of Disease (GBD) 2016. As informações seguiram padrões internacionais de certificação de óbito, através de sistemas de informação sobre estatísticas vitais e vigilância da mortalidade, pesquisas e registros hospitalares. Empregaram-se técnicas para padronização das causas de morte pelo método direto, e correções para sub-registro dos óbitos e garbage codes. Para determinar o número de mortes por cada causa, aplicou-se o algoritmo CODEm (Modelagem Agrupada de Causas de Morte). Estimaram-se os anos saudáveis de vida perdidos (DALYs) e o SDI (renda per capita, nível de escolaridade e taxa de fertilidade total) para cada país. Resultados: Existem grandes diferenças na importância relativa da carga de DCV nos PLP relacionadas principalmente às condições socioeconômicas. Entre as DCV, a doença isquêmica do coração foi a principal causa de morte nos PLP em 2016, com exceção de Moçambique e São Tomé e Príncipe, onde as doenças cerebrovasculares a suplantaram. Os fatores de risco atribuíveis mais relevantes para as DCV entre os PLP foram a hipertensão arterial e os fatores dietéticos. Um valor de p < 0,05 foi considerado significativo. Conclusão: A colaboração entre os PLP poderá permitir que experiências exitosas no combate às DCV sejam compartilhadas entre esses países.

Comparison Between Different Strategies of Rheumatic Heart Disease Echocardiographic Screening in Brazil: Data From the PROVAR (Rheumatic Valve Disease Screening Program) Study.

BACKGROUND: Considering the limited accuracy of clinical examination for early diagnosis of rheumatic heart disease (RHD), echocardiography has emerged as an important epidemiological tool. The ideal setting for screening is yet to be defined. We aimed to evaluate the prevalence and pattern of latent RHD in schoolchildren (aged 5-18 years) and to compare effectiveness of screening between public schools, private schools, and primary care centers in Minas Gerais, Brazil. METHODS AND RESULTS: The PROVAR (Rheumatic Valve Disease Screening Program) study uses nonexperts and portable and handheld devices for RHD echocardiographic screening, with remote interpretation by telemedicine, according to the 2012 World Heart Federation criteria. Compliance with study consent and prevalence were compared between different screening settings, and variables associated with RHD were analyzed. In 26 months, 12 048 students were screened in 52 public schools (n=10 901), 2 private schools (n=589), and 3 primary care centers (n=558). Median age was 12.9 years, and 55.4% were girls. Overall RHD prevalence was 4.0% borderline (n=486) and 0.5% definite (n=63), with statistically similar rates between public schools (4.6%), private schools (3.5%), and primary care centers (4.8%) (P=0.24). The percentage of informed consents signed was higher in primary care centers (84.4%) and private schools (66.9%) compared with public schools (38.7%) (P<0.001). Prevalence was higher in children ≥12 years (5.3% versus 3.1%; P<0.001) and girls (4.9% versus 4.0%; P=0.02). Only age (odds ratio, 1.12; 95% confidence interval, 1.09-1.17; P<0.001) was independently associated with RHD. CONCLUSIONS: RHD screening in primary care centers seems to achieve higher coverage rates. Prevalence among schoolchildren is significantly high, with rates higher than expected in private schools of high-income areas. These data are important for the formulation of public policies to confront RHD.

Time From Smoking Cessation and Inflammatory Markers: New Evidence From a Cross-Sectional Analysis of ELSA-Brasil.

INTRODUCTION: The time for inflammatory markers of former smokers to revert to never smoker levels is still controversial, ranging from 5 to 20 years. We aimed to determine the time from smoking cessation for white blood cell (WBC) count and serum C-reactive protein (CRP) levels to return to those of never-smokers, after adjusting for confounding factors and for secondhand smoke (SHS) exposure among participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: Cross-sectional analysis of baseline participants of ELSA-Brasil. We used linear regression analysis and generalized linear models with gamma distribution and logarithmic link function to estimate the association of WBC count and CRP levels with time from smoking cessation. The following confounding factors were considered: sex, age, education, SHS, alcohol consumption, leisure-time physical activity, BMI, total cholesterol/HDL ratio, hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease (COPD). Results: After all adjustments, time from smoking cessation <10 years remained associated with higher WBC count (eg, time from smoking cessation ≥ 5 and <10 years: ß: 167.92; 95%CI: 23.52 312.31), while only time from smoking cessation <1 year remained associated with higher arithmetic mean of CRP (AMR: 1.26, 95%CI: 1.03‒1.54). CONCLUSIONS: Levels of inflammatory markers were similar to those of never-smokers 1 year after smoking cessation for CRP and 10 years after for WBC. IMPLICATIONS: The results may add to the arsenal health professionals have to encourage their patients to quit smoking, as some harms from smoking appear to revert to never-smokers' level sooner than previously reported. Longitudinal studies should confirm our findings.

Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression.

Cardiovascular Health in Brazil: Trends and Perspectives.

Brazil is a large country, with an evolving economy, but marked social inequalities. The population is formed by an admixture of native Brazilians, Europeans, and Africans; is predominantly urban; and faces rapid aging. Time trends related to health behaviors show a substantial reduction in smoking rates, but a rising prevalence of overweight and obesity, unhealthy eating habits, and insufficient physical activity. The high prevalence of hypertension and the increasing prevalence of diabetes mellitus are also causes for concern. Cardiovascular disease (CVD) has been the leading cause of mortality since the 1960s and has accounted for a substantial percentage of all hospitalizations. In 2011, CVD was responsible for 31% of all deaths, with ischemic heart disease (31%) and cerebrovascular diseases (30%) being the leading CVD causes. Despite an increase in the overall number of CVD deaths, the age-adjusted mortality rates for CVD declined 24% between 2000 and 2011. Health care delivered by Brazil's universal public health system, which focuses on primary prevention, has contributed to this achievement. However, the decline in age-adjusted mortality differs according to race, sex, and socioeconomic status with black individuals and lower-income populations sustaining the greatest impact of CVD, especially at younger ages. With one of the world's largest public health systems in terms of population coverage, Brazil has the means to implement actions to confront the high burden of CVD, focusing on health promotion and comprehensive care. Insufficient funding, low education levels, and social inequalities remain as the main barriers to be overcome.