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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

Several studies have now shown that monoclonal gammopathy of undetermined significance (MGUS) constantly precedes all multiple myelomas (MM). Risk adapted follow-up may increase chances of early diagnosis of progression and, therefore, increase the chances of a better outcome for the patient, as also shown by two long-term follow-up studies. However, in real-life patients it is still difficult to identify MGUS cases at very high risk of progression. On a previous study we showed that Severe Isotype-Matched Immunosuppression (IMI) by Hevylite® was a potential risk factor of progression for MGUS patients. We have now expanded the median follow-up time by an additional year. Methods: The clinical records of 154 MGUS patients for which a Hevylite determination was available together with monoclonal protein quantification by gel electrophoresis (EP) and free light chains by Freelite were reviewed. Samples were analyzed with Hevylite® (The Binding Site, UK) in a BNII analyzer (Siemens) according to the monoclonal protein isotype. Normal ranges were those provided by the manufacturer. Values 50% below the lower normal ranges of the immunoglobulins determined by Hevylite were defined as severe IMI. Statistical analysis done using Graph pad V5. Progression free survival (PFS) curves calculated by Kaplan-Meyer method and curve differences by Log-rank (Mantel Cox) test. Results: The median follow-up of the 154 MGUS patients (150 IgG, 20 IgA, and 27 IgM) was 944 days (range:27-3471), during which 16 progressions to MM, 3 progressions to smoldering (by plasma cell infiltration >10%) and 1 progression to Non-Hodgkin lymphoma were registered. These numbers represent an increase in 366 days of follow-up and 3 extra progressions, with respect to the previous study. The median time to progression of the cohort is now 9,5 years. Severe IMI determined by Hevylite was observed in 14% of the patients while severe immunoparesis (i.e. more than 50% suppression of the immunoglobulins not associated to the isotype of the tumor cells; e.g. suppression of IgA or IgM in an IgG MGUS) was observed in 7% of the patients. The frequency of IMI was very similar among patients of different isotypes: IgG=60%, IgA=69%, IgM=57%, (p=0.37). When patients were analyzed according to the presence/absence of severe IMI or severe immunoparesis (IP), only the presence of severe IMI was observed to be predictive of shorter time to progression (p=0.009; HR=6.3, 95% IC=1.6-24.9) as shown in Fig.1A. Patients with severe IP were as likely to progress as patients without (p=0.604; Fig.1B). Additionally, patients showing simultaneously severe IMI and involved HLC >1.5g/dL showed a median time to progression 4 times shorter than the remaining group (Fig.2). Conclusions The results obtained strengthen the conclusions obtained previously showing that severe IMI is a risk factor for MGUS progression, mainly if combined with an involved HLC greater than 1.5g/dL. This means that, potentially, with one assay, two risk factors could be easily and quickly assessed for, virtually, every MGUS patient. The limitations of this study are its retrospective nature and a moderate over-representation of higher risk MGUS groups, which is expected since, being a real-life study, these are the patients that are most likely to maintain the follow-up with the specialist. Disclosures Barbosa: The Binding Site: Employment. Pais:The Binding Site: Employment. Campos:The Binding Site: Employment.

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.

Approximately 30% of all hereditary diffuse gastric cancer (HDGC) families carry CDH1 germline mutations. The other two thirds remain genetically unexplained and are probably caused by alterations in other genes. Using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP)/sequencing, we screened 32 Portuguese families with a history of gastric cancer and 23 patients with early onset gastric cancer for CDH1 germline mutations. In probands negative for CDH1 mutations, we screened genes involved in hereditary cancer syndromes in which gastric cancer may be one of the component tumours, namely p53 (Li-Fraumeni Syndrome) and hMLH1 and hMSH2 (HNPCC). We also screened in these patients for mutations in Caspase-10, a gene inactivated in sporadic gastric cancer, and SMAD4, a gene whose inactivation in mice is associated with signet-ring cell carcinoma of the stomach. One of the families fulfilling the HDGC criteria harboured a CDH1 germline mutation, and one of the families with incomplete criteria harboured a p53 germline mutation. No mutations were identified in hMLH1 and hMSH2, and only sequence variants were found in SMAD4 and Caspase-10. The present work reports for the first time CDH1 germline mutations in Portuguese gastric cancer families, and highlights the need for p53 mutation screening in families lacking CDH1 germline mutations, in a country with one of the highest incidences of gastric cancer in the world. No evidence was found for a role of germline mutations in SMAD4 and Caspase-10 in families lacking CDH1 mutations.

Background Vascular dysfunction is an early expression of atherosclerosis and predicts cardiovascular ( CV ) events. Peripheral arterial tonometry ( PAT ) evaluates basal pulse amplitude ( BPA ), endothelial function ( PAT ratio), and wave reflection ( PAT ‐ AI x) in the digital microvessels. In Brazilian adults, we investigated the correlations of PAT responses to CV risk factors and to carotid‐femoral pulse wave velocity ( PWV ), a measure of arterial stiffness. Methods and Results In a cross‐sectional study, 1535 participants of the ELSA ‐Brasil cohort underwent PAT testing (52±9 years; 44% women). In multivariable analyses, more‐impaired BPA and PAT ratios were associated with male sex, higher body mass index ( BMI ), and total cholesterol/high‐density lipoprotein. Higher age and triglycerides were related to higher BPA , whereas lower systolic blood pressure, hypertension ( HTN ) treatment, and prevalent CV disease ( CVD ) were associated with lower PAT ratio. PAT ‐ AI x correlated positively with female sex, advancing age, systolic and diastolic blood pressures, and smoking and inversely to heart rate, height, BMI , and prevalent CVD . Black race was associated with lower BPA , higher PAT ratio, and PAT ‐ AI x. Microvessel vasodilator function was not associated with PWV . Higher PAT ‐ AI x was modestly correlated to higher PWV and PAT ratio and inversely correlated to BPA . Conclusion Metabolic risk factors are related to impaired microvessel vasodilator function in Brazil. However, in contrast to studies from the United States, black race was not associated with an impaired microvessel vasodilator response, implying that vascular function may vary by race across populations. PAT ‐ AI x relates to HTN , may be a valid measure of wave reflection, and provides distinct information from arterial stiffness.

Introduction: The prevalence of peripheral artery disease (PAD) is rising worldwide, with a considerable impact on health care systems. We aimed to characterize the recent trends in surgical, percutaneous and clinical therapeutic procedures and in-hospital outcomes of PAD among all hospitalized patients in the Brazilian Public Health System between 2008 and 2012. Methods: Nationwide data of all hospitalizations in the Brazilian Public Health System (DataSUS) database in 2008, 2010, and 2012 were analyzed regarding the frequency of hospitalizations due to PAD (endovascular - EVR, surgical revascularizations - SR and clinical treatment - CT), length of hospital stay and in-hospital mortality and associated costs to the health system. Results: The number of hospitalizations related to PAD (EVR, SR and CT) remained stable from 2008 to 2012: 28,091 and 28,151 respectively, accounting for 0.25% and 0.24% of all in-hospital procedures. However, there was a significant change in the proportions of treatment modalities used in this period. In 2008: SR = 8,001 (29%), EVR = 3,207 (11%) and CT = 16,887 (60%); in 2010: SR = 7,999 (30%), EVR = 4,020 (15%) and CT: 14,849 (55%); and in 2012: SR = 7,882 (28%), EVR = 5,044 (18%) and CT = 15,225 (54%); p Conclusion: There is an increasing proportion of EVR for PAD in Brazil, with a concomitant increase in costs, mainly related to these procedures. Our administrative data-based analysis depicts the significant rise of overall PAD mortality in Brazil, especially in clinically treated patients, emphasizing the need of controlling PAD risk factors and promoting its early diagnosis and effective management.

The modern definition of Global Health has expanded its scope beyond neglected diseases and low-income and underdeveloped countries. The current initiatives focus on improvement of health, reduction of disparities and protection against global threats, seeking for interaction with health practices, policies and systems. There has been a growing interest on Global Health research, given the epidemiological transition currently underway in low and mid-income countries and the increasing epidemiological importance of cardiovascular and other non-communicable diseases, to the detriment of infectious diseases and nutritional deficiencies. Various aspects—formerly neglected—of these diseases, such as epidemiology, prevention, diagnosis and therapy, have been addressed in Global Health publications, leading to a better understanding of the importance of health as a public good, beyond borders. Scientific evidence supports broader initiatives in which governments, foundations and the civil society must share responsibilities and funding to achieve health equity, the main goal of Global Health.

A disfunção vascular é uma manifestação precoce da aterosclerose, está relacionada a fatores de risco e prediz eventos cardiovasculares. A tonometria arterial periférica (PAT) avalia, nos vasos digitais, a amplitude do pulso basal, a função endotelial (PAT ratio) e a reflexão da onda de pulso (PAT-AIx). Neste estudo, investigamos, em adultos brasileiros, a associação das respostas obtidas pela PAT com fatores de risco cardiovascular e com a velocidade da onda de pulso carótida-femoral (VOP), medida de rigidez arterial. Trata-se de um estudo transversal, onde 1535 participantes da coorte Estudo Longitudinal da Sáude do Adulto foram submetidos à PAT (52 ± 9 anos; 35-74 anos; 44% mulheres). Os coeficientes de correlação parciais ajustados para sexo e idade foram calculados e modelos de regressão linear múltipla foram utilizados nas análises multivariadas, as quais evidenciaram que a amplitude do pulso basal maior e o PAT ratio menor, portanto compatíveis com função vascular mais prejudicada, correlacionaram-se com sexo masculino, além de IMC e colesterol total/HDL mais elevados. Adicionalmente, triglicérides elevados, PAS reduzida e a presença de doença CV prevalente correlacionaram-se com valores mais baixos do PAT ratio. O PATAIx associou-se diretamente a sexo feminino, idade, PAS, PAD e tabagismo e inversamente a frequência cardíaca, altura, IMC e doença CV prevalente. Indivíduos com raça/cor da pele preta apresentaram BPA mais baixos e PAT ratio e PAT-AIx mais elevados, quando comparados a indivíduos brancos e pardos. Quanto à relação entre as medidas de função vascular, não houve associação entre a amplitude do pulso basal ou o PAT ratio com rigidez arterial. O PAT-AIx correlacionou-se diretamente à VOP e à amplitude do pulso basal e inversamente ao PAT ratio, sugerindo que a reflexão da onda de pulso é influenciada por múltiplos componentes e fornece informações distintas em relação à rigidez arterial. Em adultos brasileiros, as medidas de função vascular digitais correlacionaram-se com fatores de risco cardiovascular metabólicos, assim como descrito em outras populações. Entretanto, a associação da raça/cor da pele preta com uma resposta vascular mais favorável para o BPA e PAT ratio é contrastante com o que foi descrito em estudos norte-americanos, levantando a hipótese que os padrões de função vascular podem diferir entre populações.

FUNDAMENTO: A criação de sistemas ou linhas de cuidado ao infarto agudo do miocárdio (IAM) tem o objetivo de otimizar o atendimento ao paciente, desde o diagnóstico precoce até o tratamento adequado e em tempo hábil. OBJETIVO: Avaliar a implantação da linha de cuidado do IAM, em Belo Horizonte, Minas Gerais, e seu impacto na mortalidade hospitalar por IAM. MÉTODOS: A linha de cuidado do IAM foi implantada em Belo Horizonte entre 2010 e 2011 com intuito de ampliar o acesso dos pacientes do sistema público de saúde ao tratamento preconizado pelas diretrizes vigentes. As equipes das unidades de pronto atendimento foram treinadas e foi implantado sistema de tele-eletrocardiografia nessas unidades. Os desfechos primários deste estudo observacional retrospectivo foram o número de internações e a mortalidade hospitalar por IAM, de 2009 a 2011. RESULTADOS: No período avaliado, 294 profissionais foram treinados e 563 ECGs foram transmitidos das unidades de pronto atendimento para as unidades coronarianas. Houve redução importante da taxa de mortalidade hospitalar (12,3% em 2009 versus 7,1% em 2011, p < 0,001), enquanto o número de internações por IAM permaneceu estável. Ocorreu aumento do custo médio de internação (média R$ 2.480,00 versus R$ 3.501,00, p < 0,001), aumento da proporção de internações contemplando diárias de terapia intensiva (32,4% em 2009 versus 66,1% em 2011, p < 0,001) e de pacientes internados em hospitais de alta complexidade (47,0% versus 69,6%, p < 0,001). CONCLUSÃO: A implantação da linha de cuidado do IAM permitiu maior acesso da população ao tratamento adequado e, consequentemente, redução na mortalidade hospitalar por IAM. BACKGROUND:The creation of an acute myocardial infarction (AMI) management systems is aimed at optimizing the management of patients from early diagnosis to proper and timely treatment. OBJECTIVE: To assess the implantation of an AMI management system in the municipality of Belo Horizonte, state of Minas Gerais, and its impact on in-hospital mortality due to AMI. METHODS: The AMI management system was implanted in the municipality of Belo Horizonte between 2010 and 2011, aiming at increasing the access of patients of the public health system to the treatment recommended by the existing guidelines. The teams at the prompt care units were trained, and the system of tele-electrocardiography was implanted in those units. The primary outcomes of this retrospective observational study were the number of admissions and in-hospital mortality due to AMI, from 2009 to 2011. RESULTS: In the period studied, 294 professionals were trained and 563 electrocardiograms (ECGs) transmitted from prompt care units to coronary units. A significant reduction was observed in the in-hospital mortality rate (12.3% in 2009 versus 7.1% in 2011, p < 0.001), while the number of admissions due to AMI remained stable. The mean cost of admission increased (mean R$ 2,480.00 versus R$ 3,501.00; p < 0.001), the proportion of admissions including intensive care unit stay increased (32.4% in 2009 versus 66.1% in 2011; p < 0.001), and the number of patients admitted to tertiary hospitals increased (47.0% versus 69.6%; p < 0.001). CONCLUSION: The AMI management system implantation increased the access of the population to proper treatment, thus reducing in-hospital mortality due to AMI.

Monoclonal gammopathy of undetermined significance (MGUS) accounts for c.a. 50% of all diagnosed plasma cell dyscrasias and is the precursor state of all multiple myelomas (MM). However, only a small number of cases will progress to a malignant state. The challenge is on how to identify these patients and, specifically, those that are at imminent risk of developing symptomatic disease. Presently, two main bio-marker based models are used in the risk assessment of MGUS patients (Mayo Clinic group and Spanish Myeloma group), however, some patients are very differently assessed by the two models. The recently developed Hevylite assay allowed, for the first time, to easily quantify the uninvolved immunoglobulin associated with the tumor isotype and therefore study the presence of isotype-matched immunosuppression (IMI). In this study we aimed at assessing the utility of this assay for MGUS risk stratification. Methods: 309 stored serum samples from 248 MGUS (164 IgG, 44 IgA, and 40 IgM) patients attending different services from our hospital. Patients were previously risk stratified according to the 2010 IMWG guidelines (Kyle et al Leukemia). Samples were analyzed with Hevylite® (The Binding Site, UK) in a BNII analyzer (Siemens) according to the monoclonal protein isotype. Normal ranges were those provided by the manufacturer. Values 50% below the lower normal ranges of the immunoglobulins determined by Hevylite were defined as severe IMI. Results: Ninety percent of the patients showed an abnormal Hevylite Ig'k/Ig'λ ratio (i.e. IgGk/IgGL for an IgG-MGUS) with the greatest percentage observed for IgA and IgM isotypes (95% abnormal ratios). Regarding the isotype-matched immunosuppression, it was observed in 56% of the samples. The frequency of IMI by Hevylite was strongly associated with MGUS risk group (p=0.013) showing a greater prevalence in the highest risk group (Fig.1). Additionally, no significant difference was observed in relation to monoclonal isotype: IgG=60%, IgA=69%, IgM=57%, (p=0.37). Classical immunoparesis (i.e., suppression of IgG and/or IgM in an IgA patient), was less frequent than IMI (43% vs 56%, p Of the 248 MGUS patients, follow-up clinical records were recovered from for 127 (107 IgG, 20 IgA) allowing us to perform a progression free survival (PFS) based on Hevylite first sample results. Severe IMI was able to differentiate two groups of patients with significantly different PFS (p=0.023) (Fig.2). On the contrary, severe suppression of either one of the non-involved immunoglobulins (e.g. classical immunoparesis) was not associated with significant greater risk of progression (p=0.309). Interestingly, there was almost the double of patients with severe IMI in comparison with severe classical immunoparesis. Conclusions The results obtained are in line with a previous study from Katzmann et al (Leukemia 2103) where Hevylite pair suppression greater than 50% predicts progression of MGUS, thus reinforcing the potential utility of this parameter as a marker for the risk assessment of monoclonal gammopathies. It also suggests that, in this context, the predictive value of IMI is more useful than that of classical immunoparesis. Figure 1 Percentage of patients with immunosuppression by MGUS risk group.*p Disclosures Pais: The Binding Site: Employment. Barbosa:The Binding Site: Employment. Campos:The Binding Site: Employment.

BACKGROUND:The creation of an acute myocardial infarction (AMI) management systems is aimed at optimizing the management of patients from early diagnosis to proper and timely treatment. OBJECTIVE: To assess the implantation of an AMI management system in the municipality of Belo Horizonte, state of Minas Gerais, and its impact on in-hospital mortality due to AMI. METHODS: The AMI management system was implanted in the municipality of Belo Horizonte between 2010 and 2011, aiming at increasing the access of patients of the public health system to the treatment recommended by the existing guidelines. The teams at the prompt care units were trained, and the system of tele-electrocardiography was implanted in those units. The primary outcomes of this retrospective observational study were the number of admissions and in-hospital mortality due to AMI, from 2009 to 2011. RESULTS: In the period studied, 294 professionals were trained and 563 electrocardiograms (ECGs) transmitted from prompt care units to coronary units. A significant reduction was observed in the in-hospital mortality rate (12.3% in 2009 versus 7.1% in 2011, p < 0.001), while the number of admissions due to AMI remained stable. The mean cost of admission increased (mean R$ 2,480.00 versus R$ 3,501.00; p < 0.001), the proportion of admissions including intensive care unit stay increased (32.4% in 2009 versus 66.1% in 2011; p < 0.001), and the number of patients admitted to tertiary hospitals increased (47.0% versus 69.6%; p < 0.001). CONCLUSION: The AMI management system implantation increased the access of the population to proper treatment, thus reducing in-hospital mortality due to AMI.

ST-elevation myocardial infarction (STEMI) is responsible for high morbidity and mortality, and new classes of drugs are being added to its treatment overtime. The real benefit versus the bleeding risk of the associations is not yet known, given the large diversity of regimens and doses. Objectives

Fundamento: A disfunção endotelial está relacionada a fatores de risco e a predição de eventos cardiovasculares. A tonometria arterial periférica (PAT) é um novo método não invasivo para avaliação da função endotelial cuja reprodutibilidade foi pouco estudada. Objetivo: Avaliar a exequibilidade e a reprodutibilidade intraobservador do exame PAT em adultos. Métodos: Os dois exames PAT foram realizados no mesmo dia e pelo mesmo examinador em 123 participantes do Estudo Longitudinal da Saúde do Adulto ELSA que investiga os determinantes de diabetes e doenças cardiovasculares. A função endotelial no método PAT é aferida pelo índice de hiperemia reativa (RHI) que avalia as mudanças na amplitude das ondas de pulso em resposta à hiperemia. A concordância das medidas de RHI foi comparada pelo método de Bland-Altman e pelo coeficiente de variação. A confiabilidade do método foi avaliada através do coeficiente de correlação intraclasse (ICC). Resultados: A média do RHI não diferiu significativamente entre os dois exames de cada participante (1,92±0,56 vs. 1,96±0,58, p=0,48). Não houve erro sistemático entre os exames (média das diferenças = -0,03±0,5). O erro da medida foi 0,35, o coeficiente de variação encontrado foi 25,8% e o ICC foi 0,76. Sexo, faixa etária e presença de obesidade não influenciaram significativamente a reprodutibilidade do método. Conclusões: O exame PAT é factível e reprodutível em adultos. A confiabilidade do método avaliada pelo ICC foi muito boa, sugerindo que o exame possa ser usado em estudos com objetivo discriminativo. A concordância foi aceitável quando comparada a outros métodos não invasivos de avaliação da função endotelial. Este desempenho torna o PAT um método promissor para a detecção da disfunção endotelial em estudos clínicos e epidemiológicos Background: Endothelial dysfunction is associated to cardiovascular risk factors and predicts cardiovascular events. Peripheral arterial tonometry (PAT) is a new non-invasive method to assess endothelial function although there is a paucity of data about its reproducibility. Objectives: To evaluate the feasibility and the intraobserver reproducibility of PAT in adults. Methods: PAT exams were performed twice in the same day in 123 participants of a cohort about the determinants of diabetes and cardiovascular diseases (Brazilian Longitudinal Study of Adult Health ELSA). Endothelial function in PAT method is measured by reactive hyperemia index (RHI) which evaluates the changes in pulse wave amplitude in response to hyperemia. Agreement of RHI values was compared by Bland-Altman method and coefficient of variation. Reliability was assessed by intraclass correlation coefficient (ICC). Results: Mean values of RHI did not differ significantly between the exams of each participant (1,92±0,56 vs. 1,96±0,58, p=0,48). There were no systematic errors between the exams (mean of differences = -0,03±0,5). Measurement error was 0,35, coefficient of variation was 25,8% and ICC was 0,76. Gender, age or the presence of obesity did not influence the reproducibility of PAT. Conclusions: PAT exam is feasible and reproducible in adults. Reliability of PAT evaluated by ICC was considered very good, suggesting its utility in studies with discriminative purposes. Agreement of PAT measurements was found acceptable when compared to other non-invasive methods of endothelial function. This performance makes PAT a promising method to detect endothelial function in clinical and epidemiological studies

Myxoma is the most common type of cardiac tumor, accounting for 30-50% of all primary cardiac tumors. Clinically, patients usually present with at least one of the classic triad of obstructive cardiac, embolic, and constitutional signs. The case is reported of a large atrial myxoma in the left atrium which caused mitral valve obstruction, leading to severe pulmonary hypertension and right heart failure, mimicking rheumatic mitral stenosis. Postoperatively, a fall occurred in the patient's pulmonary artery pressure and she showed clinical improvement.

Studies on concomitant schistosomiasis and human and experimental malaria have shown a variation in the immunospecific response, as well as an increase in the severity of both parasitoses. In the present study, a murine co-infection model was used to determine the effects of a co-infection with Schistosoma mansoni and Plasmodium berghei on the protective immunity acquired by repeated malarial infections and subsequent curative treatment with chloroquine. Our results have demonstrated that, compared to an infection with P. berghei only, the co-infection increases the malarial parasitaemia and decreases the survival rate. Indeed, mice that were immunized by infection and treatment with drug displayed no mortality whereas co-infected mice showed a reduced protective efficacy of immunization against P. berghei (mortality > 60%). Interestingly, this high mortality rate was not associated with high levels of parasitaemia. Our findings support the idea of a suppressive effect of a Schistosoma co-infection on the anti-malarial protection by immunization. This result reveals a possible drawback of the development of anti-malarial vaccines, especially considering the wide endemic areas for both parasitoses.

p48, also called Ptf1a (pancreas-specific transcription factor 1a), is a tissue-restricted bHLH (basic helix loop helix) transcription factor which is critical for pancreatic commitment during development and for the activation and maintenance of the acinar differentiation programme in the exocrine pancreas. High-level expression of exocrine digestive enzymes, a hallmark of mature acinar cells, depends largely on the trimeric complex PTF1, formed by p48, RBP-L (recombination signal-binding protein 1-like) and a class A bHLH protein. In addition, p48 induces cell-cycle exit by controlling G1/S-phase progression. However, the mechanisms that mediate PTF1-dependent gene activation are poorly understood. In the present study, we report that p48 increases transcription through two activation domains located in its N-terminal region by recruiting transcriptional co-activators. The histone acetyltransferase cofactor p/CAF {p300/CBP [CREB (cAMP-response-element-binding protein)-binding protein]-associated factor} interacts with p48 in acinar cells in vivo and is associated with the promoter region of acinar genes targeted by the PTF1 complex. p/CAF potentiates PTF1 transcriptional activity by enhancing selectively the p48 transactivation activity. p/CAF promotes the nuclear accumulation of p48 and its in vivo acetylation in Lys200. The K200R mutation abolishes the transcriptional activity of p48, as well as its capacity to functionally co-operate with RBP-L to ensure effective PTF1-driven transcription, indicating that p/CAF-mediated acetylation of p48 is required for the full transcriptional activity of PTF1. In contrast, p/CAF did not co-operate with p48 in its growth regulatory effects. These results support a critical and selective role of p/CAF in PTF1-dependent gene activation during acinar differentiation.

beta-catenin signaling is heavily involved in organogenesis. Here, we investigated how pancreas differentiation, growth and homeostasis are affected following inactivation of an endogenous inhibitor of beta-catenin, adenomatous polyposis coli (Apc). In adult mice, Apc-deficient pancreata were enlarged, solely as a result of hyperplasia of acinar cells, which accumulated beta-catenin, with the sparing of islets. Expression of a target of beta-catenin, the proto-oncogene c-myc (Myc), was increased in acinar cells lacking Apc, suggesting that c-myc expression is essential for hyperplasia. In support of this hypothesis, we found that conditional inactivation of c-myc in pancreata lacking Apc completely reversed the acinar hyperplasia. Apc loss in organs such as the liver, colon and kidney, as well as experimental misexpression of c-myc in pancreatic acinar cells, led to tumor formation with high penetrance. Surprisingly, pancreas tumors failed to develop following conditional pancreas Apc inactivation. In Apc-deficient acini of aged mice, our studies revealed a cessation of their exaggerated proliferation and a reduced expression of c-myc, in spite of the persistent accumulation of beta-catenin. In conclusion, our work shows that beta-catenin modulation of c-myc is an essential regulator of acinar growth control, and unveils an unprecedented example of Apc requirement in the pancreas that is both temporally restricted and cell-specific. This provides new insights into the mechanisms of tumor pathogenesis and tumor suppression in the pancreas.

Introduction To measure the Monoclonal Protein (MP) is essential in monoclonal gammopathies (MG) for both diagnosis and response assessment. However, the M-spike quantification may be affected by the inherent subjectivity and by the opted integration method to determine the area under the M-spike corresponding to the MP in a serum protein electrophoresis (SPE). Co-migration with other serum proteins and strong polyclonal background may also affect the MP accurate measurement. Due to its pivotal role in managing MG, and since new automatized techniques have been developed for the MP quantification, this study aims at compare different M-spike integration methods on the measurement of MP, and compare it to the new Heavy/Light chain assay (HLC/ Hevylite®), which allows to separately quantify, by automated nephelo/turbidimetry, the serum levels of IgG-K, IgG-L, IgA-K, IgA-L, IgM-K and IgM-L. Material and Methods 147 samples from 143 MGUS and MM patients were included. All the samples were analyzed by SPE (SEBIA- HYDRASYS 2) and two integration methods were used for quantifying the MP: MP1: peak defined until baseline; MP2: peak defined excluding the polyclonal part. The size of the paraprotein measured by the MP1 method was used to divide the samples in MP10g/L. Statistical analysis included Passing-Bablok (PB) and Bland-Altman (Analyse-It®) and Mann-Whitney test (GraphPad Prism). Results The MP quantification by the MP1 and MP2 methods was significantly different (medians: 7.4 g/L vs 4.1 g/L, P10g/L (MP1:-85.02% vs MP2:-28.23%; medians: 5.4g/L vs 2.2g/L, P In all analysis, MP1 correlated better than the MP2 method with the involved HLC (iHLC) (r=0.886 and r=0.87, respectively) and the total Ig (r=0.924 and r=0.9, respectively), with lower mean relative differences. The MP1 correlation with iHLC was considerably better in samples with MP>10g/L in respect to MP10g/L: iHLC=2.096+1.045PM1 (95%CI: Intercept -3.978 to 5.719; Slope: 0.8568 to 1.320), confirming that Hevylite is a useful tool for the MP quantification. Moreover, PB analysis on the summation of Heavy/Light pairs of the same immunoglobulin isotype resulted in an agreement with the levels of total Immunoglobulin (tIg) (r=0.857. PB: ∑HLC=0.1819+0.9211tIg; 95%CI: Intercept -0.9733 to 1.331; Slope: 0.8454 to 1.006), being slightly better in MP10g/L, indicating the HLC analysis is valid for small MP measurements. HLC analysis also allows measuring the uninvolved-HLC pair (uHLC), a new immunoparesis parameter than has been suggested to have prognostic value. In this study, 32/34 MM and 49/109 MGUS samples had suppressed levels of uHLC. Interestingly, the MP1 and MP2 correlation with iHLC was better in MM than in GMSI samples (r=0,864 and r=0,857, versus, r=0,678 and r=0,606, respectively), which may be due both to generally higher levels of MP or lower polyclonal background in MM samples. Furthermore, 2/109 MGUS samples resulted in a different risk-of-progression category depending on the method of M-spike integration, with the iHLC being in agreement with the MP1 in one of the samples and discordant with the other. Conclusions The MP measurement by M-spike integration until baseline correlated with the iHLC and total immunoglobulin measurement better than when the M-spike integration excludes the polyclonal part. The good agreement between the iHLC and SPE in the quantification of the monoclonal protein puts this assay as an alternative method especially relevant at low concentration levels, which may help correcting for methodology associated variability within clinical laboratories. Finally, HLC may be easier to standardize than the SPE analysis and could eliminate the need for total Ig quantification. Disclosures Pais: The Binding Site Spain: Employment. Campos:The Binding Site Spain: Employment.

Background : The outcome for patients with Multiple Myeloma (MM) is highly variable. Understanding the prognosis for a particular patient can help when selecting the intensity of treatment to be used and the frequency of reviews. The International Staging System (ISS) is the current standard used for risk stratification of patients with MM. Recent studies have evaluated the relationship between serum free light chains (sFLC) at diagnosis and the prognosis of these patients. The aim of this study is to evaluate the prognostic value of sFLC ratio (sFLCR) at baseline in newly diagnosed MM in a Southern Spanish population. Materials and Methods : 180 patients (82 Male:98 Female) with a median age of 69 years (range 61-76) were recruited and followed for up to 7 years. The median follow up of the patients was 35 (18-61) months. sFLC concentrations were measured nephelometrically (Freelite, The Binding Site, Birmingham, UK) and the sFLCR was calculated using the monoclonal sFLC as the numerator. Patients were stratified into two groups according to the median value of sFLCR: group "low" with sFLCR Results : During follow-up there were 72 disease-related deaths: 23 in group "low" and 49 in group "high". The 7-years OS of all patients was 38%, whereas it was 57% and 10% in groups "low" and "high" respectively (HR=5.07 IC95% 3.01-8.55, p65 years old, creatinine>2 mg/dL, hemoglobin3.5 mg/L, albumin3.5 mg/L allows us to include patients in a new model with three risk groups more accurate compared with ISS model (Table 2 and Figure 1). Conclusions : sFLCR value at diagnosis is an important independent risk factor for poor prognosis in patients with newly diagnosed MM. Our new staging system model based on sFLCR and B2M allow us an accurate risk stratification of patients with MM in our population. Table 1. Univariate and multivariate analysis of prognostic factors for patients with newly diagnosed MM. Variables Univariate analysis Multivariate analysis HR (95%IC) p-value HR (95%IC) p-value Age>65 years 1.99 (1.17-3.41) 0.01 - sFLC ratio≥50(involved/uninvolved) 5.07 (3.01-8.55) 11 mg/dL 1.75 (0.87-3.53) 0.2 - Hemoglobin2 mg/dL 2.15 (1.25-3.70) 0.005 - Lytic bone lesions 1.21 (0.74-1.97) 0.4 - B2M>3.5 mg/L 3.66 (2.16-6.21) 3 g/dL 1.86 (1.07-3.21) 0.03 - Plasma cell>10% 1.57 (0.92-2.71) 0.1 - ISS-2 (vs. ISS-1) 3.02 (1.56-5.73) 0.001 - ISS-3 (vs. ISS-3) 4.88 (2.50-9,52) Table 2. Prognostic value of International Staging System (ISS) and New Staging System based on sFLCR and B2M. NR=not reached. (1)p-value=0.09 between ISS-2 and ISS-3. (2)p-value3.5 mg/L or sFLCR≥50) 62 23 (37) 33 67 3.02 (1.49-6.13) 0.002 Stage 3(B2M>3.5 mg/L and sFLCR≥50) 65 37 (57) 0 35 11.60 (5.53-24.33) Figure 1. Figure 1. Disclosures Harding: The Binding Site Group Ltd: Employment, Membership on an entity's Board of Directors or advisory committees. Campos:The Binding Site Spain: Employment.

To estimate the association between 2 markers for atherosclerosis, measurements of carotid artery intima-media thickness (IMT) and of peripheral arterial tonometry (PAT), and to evaluate the role of traditional cardiovascular risk factors in this association. We applied the 2 diagnostic tests to 588 participants from the ELSA-Brazil longitudinal study cohort. The PAT measurements, obtained with the EndoPAT2000, were the reactive hyperemia index (RHI), the Framingham RHI (F-RHI), and the mean basal pulse amplitude (BPA). We used the mean of the mean scores of carotid IMT of the distal layers of the left and right common carotids obtained by ultrasonography after 3 cardiac cycles. We used linear regression and the Spearman correlation coefficient to test the relationship between the 2 markers, and multiple linear regressions to exam the relationship between the RHI/F-RHI scores and the mean BPA and IMT scores after adjusting for cardiovascular risk factors. In the multivariate analysis, RHI (but not F-RHI) was positively correlated with the mean of the means of the IMT values after adjusting for sex and risk factors connected with both measures (β = 0.05, P = 0.02). Mean BPA did not remain significantly associated with IMT after adjusting for common risk factors. We found that the higher the IMT (or the worse the IMT), the higher the RHI (or the better the endothelial function). F-RHI was not associated with IMT. These 2 results are against the direction that one would expect and may imply that digital endothelial function (RHI and F-RHI) and IMT correspond to distinct and independent stages of the complex atherosclerosis process and represent different pathways in the disease's progression. Therefore, IMT and PAT measures may be considered complementary and not interchangeable.

Background & Aims: Pro-inflammatory polymorphisms within the genes interleukin (IL)-1B and IL-1RN are associated with risk for gastric carcinoma (GC) in Helicobacter pylori —infected individuals. We aimed to determine the association between variation of the tumor necrosis factor ( TNF )-α gene and the risk for chronic atrophic gastritis (CAG) and GC. We also investigated the extent to which the combined effect of proinflammatory genetic polymorphisms ( IL-1B , IL-1RN , and TNF- α), and the combined effect of TNF -α and bacterial genotypes each influence such a risk. Methods: In a case-control study including 306 controls, 221 individuals with chronic gastritis, and 287 GC patients, the TNF- α-308 and IL-1B -511 bi-allelic polymorphisms, the IL-1RN variable number of tandem repeats (VNTR), and the H. pylori genes vacA (s and m regions) and cagA were genotyped. Results: We found that carriers of the TNF- α-308∗A allele are at increased risk for GC development with an odds ratio (OR) of 1.9 (95% confidence interval [CI], 1.3–2.7). For both CAG and GC, the odds of developing disease increased with the number of high-risk genotypes. Individuals carrying high-risk genotypes at the 3 loci are at increased risk for CAG and GC with an OR of 5.8 (95% CI, 1.1–31.0) and 9.7 (95% CI, 2.6–36.0), respectively. The risk for GC was not affected significantly by the combination of bacterial and TNF- α-308 genotypes. Conclusions: These findings show that a proinflammatory polymorphism in the TNF -α gene is associated with increased risk for GC, and that it is possible to define a specific genetic profile associated with highest risk for CAG and GC.

Endomyocardial fibrosis (EMF) is a neglected tropical disease that affects millions of people worldwide. EMF is the most common cause of restrictive cardiomyopathy, caused by deposition of fibrous tissue on endocardial surfaces. EMF is a major cause of death in areas where it is endemic, but the pathogenesis of the disease is poorly understood. Schistosomiasis mansoni is a parasitic disease endemic in Brazil, where EMF has also been described. The association between EMF and schistosomiasis has been suggested in various publications, seeking a possible correlation between endocardial and periportal fibroses. This report describes a case of EMF associated with schistosomiasis. A endomiocardiofibrose (EMF) é uma doença tropical, negligenciada, que afeta milhões de pessoas no mundo. É considerada a causa mais comum de cardiomiopatia restritiva, causada pela deposição de tecido fibroso em superfícies endocárdicas. Endomiocardiofibrose é uma das principais causas de morte em áreas onde é endêmica, e sua patogênese é pouco conhecida. A esquistossomose mansoni é uma doença parasitária endêmica no Brasil, onde a EMF também tem sido descrita. Tem sido apontada associação entre EMF e esquistossomose em várias publicações, buscando-se uma possível correlação entre a fibrose endocárdica e periportal. Neste relato, descreve-se um caso de EMF associado a esquistossomose.

Background Recent studies have shown that Serum Free Light Chain (sFLC) levels correlate with Systemic Lupus Erythematosus (SLE) disease activity, a result not demonstrated for C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). Due to the short half-life (2 -6h) of the circulating sFLC, they may be of advantage to identify changes of disease activity in comparison to other laboratory assays. Objectives Objective: to evaluate the total sFLC (∑FLC = sFLC-κ + sFLC-λ) levels in SLE patients, and compare the polyclonal sFLC increases with specific disease activity markers. Methods 79 SLE patients previously diagnosed that fulfilled at least 4 ACR criteria were studied, together with 23 control samples from unrelated patients without known rheumatologic disease. Serum protein electrophoresis was preformed to discard the presence of a monoclonal protein. Analyzed parameters: sFLC, total immunoglobulins, anti-double stranded DNA (anti-dsDNA) and anti-nuclear antibodies (ANAS), C-reactive protein (CRP), Creatinine (Cre), C3 and C4. Spearman correlations, Mann-Whitney and ANOVA analysis were done by GraphPad Prism software. Results 79 SLE patients were studied. Because SLE patient’s frecuently have renal impairment that may lead to increased serum levels of sFLC, 4 patients with increased Cre were excluded from further analysis. Correlations were found between ∑FLC and Cre (r=0,2706, P=0,0181), C3 (r= -0,4070, P=0,0006) and C4 (r= -0,3179, P=0,0088). dsDNA-negative, dsDNA-positive, ANAS-negative and ANAS-positive groups’ ∑FLC medians were significantly different from control median. More interestingly, the dsDNA–positive and –negative ∑FLC median were significantly different (P Conclusions The results observed indicate that the ∑sFLC may distinguish two groups within the dsDNA-positive patients. These results may suggest a potential activity marker that adds information to the patient’s disease activity. Having a short half-life in the serum, the sFLC determination may allow to observe activity changes in a more timely fashion. Further prospective studies in our lab will evaluate the value of a new “activity algorithm” based on the dsDNA, C3 and C4determinations together with sFLC, needed to confirm the value of sFLC in evaluating disease activity. Disclosure of Interest None Declared

Creating evidence-based systems of care for acute myocardial infarction (AMI) aims to optimize patient care, from early diagnosis to appropriate treatment in optimal time frames, in accordance to current guidelines. To evaluate the effects of an AMI System of Care in a large metropolitan area in

RESUMO: Objetivo: Analisar as variações e os diferenciais da mortalidade por doenças cardiovasculares (DCV) no Brasil e em seus estados, em 1990 e 2015. Métodos: Foram utilizados os dados de mortalidade compilados pelo Global Burden of Disease (GBD) 2015, obtidos da base de dados do Sistema de Informação sobre Mortalidade do Ministério da Saúde. Foram realizadas a correção do sub-registro de óbitos e a reclassificação dos códigos garbage por meio de algoritmos específicos. As causas cardiovasculares foram subdivididas em 10 causas específicas. As taxas de mortalidade - dos anos 1990 e 2015 - foram padronizadas pela idade, de acordo com o sexo e o estado brasileiro. Resultados: A taxa de mortalidade por DCV padronizada por idade caiu de 429,5 (1990) para 256,0 (2015) a cada 100 mil habitantes (40,4%). A redução proporcional foi semelhante em ambos os sexos, mas as taxas em homens são substancialmente mais altas do que nas mulheres. A redução da taxa padronizada por idade foi mais acentuada para a doença cardíaca reumática (44,5%), cardiopatia isquêmica (43,9%) e doença cerebrovascular (46,0%). A queda na mortalidade diferiu marcadamente entre os estados, sendo mais acentuada nos estados das regiões Sudeste e Sul do país e no Distrito Federal, e atenuada nos estados do Norte e Nordeste. Conclusão: A mortalidade por DCV padronizada por idade reduziu no Brasil nas últimas décadas, porém de forma heterogênea entre os estados e para diferentes causas específicas. Considerando a magnitude da carga de doença e o envelhecimento da população brasileira, as políticas de enfrentamento das DCV devem ser priorizadas. ABSTRACT: Objective: To analyze variations and particularities in mortality due to cardiovascular disease (CVD) in Brazil and in Brazilian states, in 1990 and 2015. Methods: We used data compiled from the Global Burden of Disease (GBD) 2015, obtained from the database of the Mortality Information System (SIM) of the Brazilian Ministry of Health. Correction of the sub-registry of deaths and reclassification of the garbage codes were performed using specific algorithms. The cardiovascular causes were subdivided into 10 specific causes. Age-standardized CVD mortality rates - in 1990 and 2015 - were analyzed according to sex and Brazilian state. Results: Age-standardized CVD mortality rate decreased from 429.5 (1990) to 256.0 (2015) per 100,000 inhabitants (40.4%). The proportional decrease was similar in both sexes, but death rates in males were substantially higher. The reduction of age-standardized mortality rate was more significant for rheumatic heart disease (44.5%), ischemic cardiopathy (43.9%), and cerebrovascular disease (46.0%). The decline in mortality was markedly different across states, being more pronounced in those of the southeastern and southern regions and the Federal District, and more modest in most states in the north and northeast regions. Conclusion: Age-standardized CVD mortality has declined in Brazil in recent decades, but in a heterogeneous way across states and for different specific causes. Considering the burden magnitude and the Brazilian population aging, policies to prevent and manage CVD should continue to be prioritized.

Objectives Endothelial dysfunction is associated to cardiovascular risk factors and predicts cardiovascular events. Peripheral arterial tonometry (PAT) is a novel noninvasive method to assess endothelial function. However, there is a paucity of data about its reproducibility. The aim of this study was to assess the feasibility and reproducibility of PAT in adults. Methods PAT exams were performed twice in the same day in 123 participants of a cohort about the determinants of diabetes and cardiovascular diseases (Brazilian Longitudinal Study of Adult Health--ELSA-Brasil). The interval between the exams was 2-6 h (mean=4 h). Endothelial function in PAT method is measured by reactive hyperemia index (RHI), which evaluates arterial pulsatile volume changes in response to hyperemia. Agreement of RHI values was compared by Bland-Altman method, coefficient of variation and coefficient of repeatability. Reliability was assessed by intraclass correlation coefficient (ICC). Results Mean values of RHI did not differ significantly between the exams of each participant (1.92±0.56 vs. 1.96±0.58, P=0.48). There were no systematic errors between the exams (mean of differences=-0.03±0.5). Measurement error was 0.35, coefficient of variation was 18.0% and ICC was 0.61. Sex, age or the presence of obesity did not have a considerable influence on the reproducibility of PAT. Conclusion PAT exam is feasible and has acceptable reproducibility in adults when compared with other noninvasive methods for endothelial function assessment. This performance makes PAT a promising method for future clinical and epidemiological studies.

INTRODUÇÃO: As doenças cardiovasculares (DCV) são a principal causa de morbimortalidade no mundo moderno. O eletrocardiograma (ECG) é ferramenta útil na avaliação dessas doenças, de baixo custo e amplamente disponível. Seu uso como potencial marcador prognóstico em prevenção primária das DCV, já foi explorado, mas não bem definido. MÉTODOS: Estudo de coorte com dados de 13428 adultos (45% homens, idade 35-74 anos) do Estudo Longitudinal de Saúde do Adulto sem DCV na linha de base. O ECG foi codificado de acordo com o código de Minnesota (CM). O objetivo principal é a avaliar o impacto prognóstico de alterações eletrocardiográficas maiores (AEM) codificadas pelo CM. Para tal, sua relação com mortalidade, em seguimento médio de oito anos, foi avaliada pelas curvas de Kaplan-Meier e comparadas pelo teste de log rank. Em análise por modelo de Cox, ajustado por fatores de risco cardiovascular e sociodemográficos, avaliamos ainda o papel das AEM como preditores de mortalidade geral e, posteriormente cardiovascular por meio do modelo de risco competitivo de Fine and Gray. O potencial de reclassificação de risco foi avaliado índice de reclassificação líquida, incorporando as AEM ao cálculo de risco cardiovascular pelo Systematic Coronary Risk Evaluation (SCORE). Os ECG dos participantes foram repetidos após seguimento médio de 4 anos, sendo feita a avaliação de determinantes da incidência de AEM. Estas análises foram feitas estratificadas pro sexo. RESULTADOS: As AEM se associaram a maior risco de morte geral (HR 2.3 IC 95% 1.7-2.9) e cardiovascular (HR 4.6 IC 95% 3.0-7.0), após análise multivariada. As alterações maiores do segmento ST-T, os bloqueios intraventriculares e o prolongamento maior do intervalo QT foram as alterações mais impactantes. A presença de AEM foi capaz de reclassificar corretamente 15% dos participantes classificados como de risco intermediário pelo SCORE (para um grupo de risco mais alto) que vieram a apresentar o desfecho de mortalidade por DCV, as custas de 3% de reclassificações erradas (também para um grupo de maior risco) dentre os participantes que sobreviveram durante o seguimento. A incidência de AEM foi semelhante em homens e mulheres (10,9% e 11,1% respectivamente). Não identificamos fatores associados a incidência de AEM. CONCLUSÕES: As AEM foram preditores independentes de mortalidade geral e cardiovascular na população estudada. A reclassificação líquida de participantes de risco CV intermediário foi positiva. A incidência de AEM em quatro anos foi alta, mas preditores para seu surgimento não foram identificados. BACKGROUND: Cardiovascular diseases (CVD) are the main cause of morbimortality worldwide. The electrocardiogram (ECG) is a low-cost, widely available and frequently used diagnostic tool in the care of the patient with cardiovascular complaints. Nevertheless, its role in determining CVD prognosis as well as in the screening for CVD is still unclear. METHODS: This is a cohort, study with data from 13428 adults (45% men, age 35-74 years old) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included the ECG, coded according to the Minnesota Coding System (MC). Its main goal is to evaluate the prognostic impact of major electrocardiographic abnormalities (MEA) according to the MC. Mortality was analyzed through Kaplan-Meier curves and compared by the log rank test. Adjustment for cardiovascular and sociodemographic risk factors were made by Cox regression. Cardiovascular mortality risk was evaluated by the Fine and Gray competitive risk model. We also evaluated the potential of MEA in reclassifying the participants’ cardiovascular mortality risk calculated by the Systematic Coronary Risk Evaluation (SCORE) using the net reclassification index. After a four-year follow up, new ECG data was obtained and the incidence of new MEA was measured with its possible determinants evaluated. This particular analysis was stratified by sex. RESULTS: Participants with baseline MEA were in general of higher CVD risk. After multivariable analysis, the presence of MEA was still an independent predictor of total mortality (HR 2.3, 95% CI 1.7-2.9) and cardiovascular mortality (HR 4.6 IC 95% 3.0-7.0). Among the MEA analyzed, major ST-T abnormalities, intraventricular blocks and major QT interval prolongation were the most relevant. In adding MEA to the SCORE risk prediction tool, we were able to accurately reclassify 15% of intermediate risk individuals to a high-risk stratum. In the other hand among survivors, 3% were miss-reclassified from intermediate to a high-risk category. In a four-year follow up, the incidence of MEA was similar between men and women without prevalent CVD or MEA (10.9% and 11.1% respectively). For this short period we were not able to identify any predictors for incident MEA. CONCLUSIONS: The presence of major electrocardiographic abnormalities according to the Minnesota coding system, were independent predictors of general and cardiovascular mortality in the studied population. We achieved a favorable net reclassification index for the participants within the intermediate risk category. Incident MEA in four years was high, even though no clinical predictors were identified.

Introdução: As disfunções endotelial e autonômica estão associadas ao desenvolvimento de doenças cardiovasculares, e uma via fisiopatológica comum para ambas tem sido descrita. No entanto, ainda é pouco explorada a associação entre as funções autonômica e endotelial microvascular avaliadas por métodos não invasivos - variabilidade da frequência cardíaca (VFC) e tonometria arterial periférica (TAP), respectivamente. Participantes e métodos: Em 1.447 participantes do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) foi investigada a correlação entre variáveis das funções endotelial microvascular e autonômica utilizando o teste de correlação de Spearman. Análise de subgrupos foi realizada em indivíduos com diabetes mellitus, com sobrepeso / obesidade, com síndrome metabólica e em indivíduos sem fatores de risco cardiovascular. Realizou-se ainda análise de sensibilidade em indivíduos sem DCV prevalente e naqueles que não estavam em uso de bloqueadores beta-adrenérgicos, bloqueadores dos canais de cálcio e agonistas alfa-adrenérgicos. Resultados: Encontrou-se correlações fracas entre amplitude de pulso basal (BPA) e intervalo RR médio (0,064), RMSSD (0,067) e HF (-0,093), e entre PAT-ratio e RMSSD (0,058) e HF (0,067). As correlações observadas permaneceram fracas após análises de subgrupo e de sensibilidade. Conclusão: A associação entre a função endotelial avaliada na microvasculatura e a função autonômica avaliada pela análise da VFC não é clinicamente relevante, sugerindo que elas podem contribuir para o desenvolvimento de doenças cardiovasculares por meio de diferentes mecanismos Introduction: Endothelial and autonomic dysfunctions are thought to be associated with the development of cardiovascular diseases, and a common pathway for both dysfunctions has been described. However, the association between autonomic and microvascular endothelial functions assessed by non-invasive methods - heart rate variability (HRV) and peripheral arterial tonometry (PAT), respectively - has been little explored. Participants and methods: In 1,447 participants of the Brazilian Longitudinal Study of Adult Health (ELSABrasil), we investigated the correlation between endothelial microvascular and autonomic functions variables using Spearmans rank correlation test. Subgroup analysis was pre-specified in individuals with diabetes, overweight/obesity, metabolic syndrome, and individuals free of cardiovascular risk factors. Sensitivity analysis was performed for individuals without prevalent CVD and for participants who were not using beta-adrenergic blockers, calcium-channel blockers and alpha-adrenergic agonists. Results: We found weak correlations between basal pulse amplitude (BPA) and mean RR interval (0.064), RMSSD (0.067) and HF (-0.093), and between PAT-ratio and RMSSD (0.058) and HF (0.067). The observed correlations remained weak in subgroup and sensitivity analysis. Conclusion: The association between endothelial function evaluated in the microvasculature and autonomic function assessed by HRV analysis is not relevant, suggesting that they may contribute in different pathways to the development of cardiovascular diseases

INTRODUÇÃO: O eletrocardiograma (ECG) é uma ferramenta amplamente utilizada em estudos epidemiológicos, mas existem poucos estudos de base populacional na América Latina e no Brasil. O Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil), que incluiu 15105 participantes (35 74 anos) de seis capitais brasileiras, permitiu a criação de base de dados eletrocardiográficos dessa população. O objetivo deste trabalho é descrever as medidas eletrocardiográficas em adultos brasileiros não portadores de doença cardiovascular e avaliar as alterações eletrocardiográficas maiores, segundo o código de Minnesota, por sexo, idade, raça e fatores de risco cardiovascular.MÉTODOS: Estudo transversal no qual foram obtidos dados de 14424 adultos (45,8% homens, idade 35-74 anos) na linha de base do ELSA-Brasil, através de entrevistas e exames clínicos e laboratoriais. Os ECG foram obtidos no aparelho BurdickAtria 6100, armazenados pelo Sistema Pyramis, codificados automáticamente conforme código de Minnesota pelo software da Universidade de Glasgow e as alterações maiores revistas manualmente. A distribuição das medidas eletrocardiográficas em pacientes livres de doença cardiovascular e que declararam a raça (n=11094, 44,5% homens) foram descritascomo mediana (intervalo interquartil).A prevalência das alterações eletrocardiográficas maiores foram descritas e estratificadas por sexo, grupo de idade, cor/raça autodeclarada e número de fatores de risco cardiovascular. Para comparação entre os grupos citados, foi utilizado o teste Quiquadrado. RESULTADOS: As medianas dos medidas eletrocardiográficas analisadas forampara homens e mulheres, respectivamente: frequência cardíaca 63vs66bpm, intervalo PR 164vs158ms, intervalo QTc 410vs421ms, duração do QRS92x86ms, duração da onda P 112vs108ms, eixo da onda P 54vs57 graus, eixo da onda R 35vs39 graus, havendo diferença para todas as variáveis analisadas (p