RESUMO
Rheumatic fever (RF) and chronic rheumatic heart disease (RHD) are complications of oropharyngeal infection caused by Streptococcus pyogenes. Despite the importance of the complement system against infections and autoimmunity diseases, studies on the role of the lectin pathway in RF and RHD are scarce. Thus, our aim was to evaluate the association of ficolin-3 serum levels, FCN3 polymorphisms and haplotypes with the susceptibility to RF and RHD. We investigated 179 patients with a history of RF (126 RHD and 53 RF only) and 170 healthy blood donors as control group. Ficolin-3 serum concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Three FCN3 single nucleotide polymorphisms (SNPs rs532781899, rs28362807 and rs4494157) were genotyped through the sequence-specific PCR method. Lower ficolin-3 serum levels were observed in RF patients when compared to controls (12.81 µg/mL vs. 18.14 µg/mL respectively, p < 0.0001, OR 1.22 [1.12-1.34]), and in RHD in comparison to RF only (RFo) (12.72 µg/mL vs. 14.29 µg/mL respectively, p = 0.016, OR 1.38 [1.06-1.80]). Low ficolin-3 levels (<10.7 µg/mL) were more common in patients (39.5 %, 30/76) than controls (20.6 %, 13/63, p = 0.018, OR = 2.51 [1.14-5.31]), and in RHD (44.4 %, 28/63) than RFo (15.4 %, 2/13, p = 0.007, OR = 3.08 [1.43-6.79]). On the other hand, FCN3 polymorphism/haplotypes were not associated with ficolin-3 serum levels or the disease. Low ficolin-3 levels might be associated with RF, being a potential marker of disease progression.
Assuntos
Suscetibilidade a Doenças , Lectinas/genética , Febre Reumática/etiologia , Febre Reumática/metabolismo , Cardiopatia Reumática/etiologia , Adulto , Alelos , Biomarcadores , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Lectinas/sangue , Lectinas/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Febre Reumática/diagnóstico , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/metabolismoRESUMO
Rheumatic heart disease (RHD) remains a major cause of preventable death and disability in children and young adults. Despite significant advances in medical technology and increased understanding of disease mechanisms, RHD continues to be a serious public health problem throughout the world, especially in low- and middle-income countries. Echocardiographic screening has played a key role in improving the accuracy of diagnosing RHD and has highlighted the disease burden. Most affected patients present with severe valve disease and limited access to life-saving cardiac surgery or percutaneous valve intervention, contributing to increased mortality and other complications. Although understanding of disease pathogenesis has advanced in recent years, key questions remain to be addressed. Preventing or providing early treatment for streptococcal infections is the most important step in reducing the burden of this disease.
Assuntos
Cardiopatia Reumática , Ecocardiografia , Humanos , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/prevenção & controleRESUMO
Abstract Rheumatic heart disease (RHD) remains a major cause of preventable death and disability in children and young adults. Despite significant advances in medical technology and increased understanding of disease mechanisms, RHD continues to be a serious public health problem throughout the world, especially in low- and middle-income countries. Echocardiographic screening has played a key role in improving the accuracy of diagnosing RHD and has highlighted the disease burden. Most affected patients present with severe valve disease and limited access to life-saving cardiac surgery or percutaneous valve intervention, contributing to increased mortality and other complications. Although understanding of disease pathogenesis has advanced in recent years, key questions remain to be addressed. Preventing or providing early treatment for streptococcal infections is the most important step in reducing the burden of this disease.
Assuntos
Humanos , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/prevenção & controle , Cardiopatia Reumática/diagnóstico por imagem , EcocardiografiaRESUMO
Rheumatic fever (RF) and rheumatic heart disease (RHD) follow untreated S. pyogenes throat infections in children who present susceptible genes that favor the development of autoimmune reactions. In this review, we focus on the genes that confer susceptibility and on the autoimmune reactions that occur due to molecular mimicry between human-tissue proteins and streptococcal M protein. Polyarthritis is the initial manifestation, which can evolve to carditis and severe valve damage; these culminate in rheumatic heart disease (RHD) or Sydenham's chorea, which affects the central nervous system. A perspective on vaccine development to prevent the disease is also discussed.
Assuntos
Cardiopatia Reumática/metabolismo , Cardiopatia Reumática/prevenção & controle , Vacinas/uso terapêutico , Autoimunidade , Coreia/etiologia , Coreia/imunologia , Coreia/metabolismo , Coreia/prevenção & controle , Citocinas/metabolismo , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Mimetismo Molecular , Febre Reumática/etiologia , Febre Reumática/imunologia , Febre Reumática/metabolismo , Febre Reumática/prevenção & controle , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/imunologia , Streptococcus pyogenesRESUMO
BACKGROUND: Rheumatic heart disease remains a major health problem in developing countries. Several factors contribute to valve-related morbidity after cardiac surgery, but the role of rheumatic etiology of valve disease is not well defined. This study was designed to determine the additional value of rheumatic valve disease in predicting morbidity after cardiac surgery in the current era of heart valve disease treatment. METHOD: This study prospectively included 164 patients for cardiac surgery from June 2010 to June 2011. The outcome was prolonged length of stay, defined as a length of stay greater than or equal to the 75th percentile for length of stay for each operation, including the day of discharge. RESULTS: Rheumatic heart disease was present in 32 patients (20%) and all rheumatic patients underwent valve replacement. Rheumatic heart disease patients were younger with less comorbidities compared to non-rheumatic patients, with most (63%) having had previous surgery. Forty-one patients were classified as having a prolonged hospital length of stay; 11 (34%) patients with rheumatic and 30 (23%) non-rheumatic fever. Rheumatic heart disease was not associated with prolonged hospital stay in the univariate analysis; however, after adjustment for other factors including infectious endocarditis, surgery duration, mechanical ventilation time, EuroSCORE, and postoperative pneumonia, it was found to be a predictor of prolonged hospitalization. CONCLUSION: This study demonstrates that rheumatic heart disease was an important factor associated with prolonged hospital, after adjustment for well-known risk factors of morbidity after cardiac surgery. Rheumatic fever is still prevalent among the patients who underwent to cardiac surgery in the current age, contributing to increase the postoperative morbidity.
OBJETIVO: A doença cardíaca reumática continua a ser um problema grave de saúde nos países em desenvolvimento. Vários fatores contribuem para a morbidade relacionada com a cirurgia valvar cardíaca, mas o papel da etiologia reumática das valvopatias não está bem definido. Este estudo foi desenhado para determinar participação adicional de valvopatias reumáticas na previsão de morbidade após cirurgia cardíaca na era atual de tratamento da doença. MÉTODOS: Este estudo incluiu prospectivamente 164 pacientes submetidos a cirurgia cardíaca, entre junho de 2010 a junho de 2011. O resultado medido foi a duração da estadia prolongada, definido como tempo de permanência maior ou igual ao percentil 75 para a duração da estada para cada operação, incluindo a dia da alta. RESULTADOS: A cardiopatia reumática esteve presente em 32 pacientes (20%) e em todos os pacientes submetidos à substituição da válvula. Pacientes com doenças cardíacas reumáticas eram mais jovens e com menos comorbidades comparados com pacientes não-reumáticos; a maioria deles (63%) tinha tido cirurgia prévia. Quarenta e um pacientes foram classificados como tendo um tempo de permanência hospitalar prolongado; 11 (34%) pacientes com doenças reumáticas e 30 (23%) com doenças não-reumáticas. A doença reumática não se apresentou associada com período de internação prolongado, na análise univariada; No entanto, após o ajuste para outros fatores, incluindo endocardite infecciosa, duração da cirurgia, tempo de ventilação mecânica, EuroSCORE, e pneumonia no pós-operatório, a doença reumática revelou-se um preditor de hospitalização prolongada. CONCLUSÕES: Este estudo demonstra que a doença cardíaca reumática é um importante fator associado com internação prolongada, após o ajuste para fatores de risco bem conhecidos de morbidade após cirurgia cardíaca. A febre reumática ainda é prevalente entre os pacientes que se submeteram à cirurgia cardíaca na época atual, contribuindo para aumentar a morbidade pós-operatória.
Assuntos
Humanos , Cuidados Pós-Operatórios , Cardiopatia Reumática/etiologia , Cirurgia Torácica , Implante de Prótese de Valva Cardíaca , Tempo de InternaçãoRESUMO
Rheumatic fever (RF) is an autoimmune disease caused by the Gram-positive bacteria Streptococcus pyogenes following an untreated throat infection in susceptible children. Rheumatic heart disease (RHD), the most serious complication, occurs in 30-45% of RF patients and leads to chronic valvular lesions. Here, we focus on the genes that confer susceptibility for developing this disease. Molecular mimicry mediates the cross-reactions between streptococcal antigens and human proteins. Several autoantigens have been identified, including cardiac myosin epitopes, vimentin, and other intracellular proteins. In heart tissue, antigen-driven oligoclonal T cell expansions probably cause the rheumatic heart lesions. These cells are CD4+ and produce inflammatory cytokines (TNF alpha and IFN gamma). IL-4+ cells are found in the myocardium; however, these cells are very scarce in the valve lesions of RHD patients. IL-4 is a Th2-type cytokine and plays a regulatory role in the inflammatory response mediated by Th1 cytokines. Our findings indicate that the Th1/Th2 cytokine balance has a role in healing myocarditis while the low numbers of IL-4-producing cells in the valves probably induced the progressive and permanent valve damage.
Assuntos
Cardiopatia Reumática/etiologia , Predisposição Genética para Doença , Humanos , Interleucina-4/fisiologia , Mimetismo Molecular , Cardiopatia Reumática/genética , Cardiopatia Reumática/imunologia , Células Th1/imunologiaRESUMO
BACKGROUND: Rheumatic fever (RF) and rheumatic heart disease (RHD) are still major medical and public health problems mainly in developing countries. Pilot studies conducted during the last five decades in developed and developing countries indicated that the prevention and control of RF/RHD is possible. During the 1970s and 1980s, epidemiological studies were carried out in selected areas of Cuba in order to determine the prevalence and characteristics of RF/RHD, and to test several long-term strategies for prevention of the diseases. METHODS: Between 1986 and 1996 we carried out a comprehensive 10-year prevention programme in the Cuban province of Pinar del Rio and evaluated its efficacy five years later. The project included primary and secondary prevention of RF/RHD, training of personnel, health education, dissemination of information, community involvement and epidemiological surveillance. Permanent local and provincial RF/RHD registers were established at all hospitals, policlinics and family physicians in the province. Educational activities and training workshops were organised at provincial, local and health facility level. Thousands of pamphlets and hundreds of posters were distributed, and special programmes were broadcast on the public media to advertise the project. RESULTS: There was a progressive decline in the occurrence and severity of acute RF and RHD, with a marked decrease in the prevalence of RHD in school children from 2.27 patients per 1,000 children in 1986 to 0.24 per 1,000 in 1996. A marked and progressive decline was also seen in the incidence and severity of acute RF in five- to 25-year-olds, from 18.6 patients per 100,000 in 1986 to 2.5 per 100,000 in 1996. There was an even more marked reduction in recurrent attacks of RF from 6.4 to 0.4 patients per 100,000, as well as in the number and severity of patients requiring hospitalisation and surgical care. Regular compliance with secondary prophylaxis increased progressively and the direct costs related to treatment of RF/RHD decreased with time. The implementation of the programme did not incur much additional cost for healthcare. Five years after the project ended, most of the measures initiated at the start of the programme were still in place and occurrence of RF/RHD was low.
Assuntos
Serviços de Saúde Comunitária , Países em Desenvolvimento , Atenção Primária à Saúde , Prevenção Primária , Febre Reumática/prevenção & controle , Cardiopatia Reumática/prevenção & controle , Prevenção Secundária , Adolescente , Adulto , Atitude do Pessoal de Saúde , Criança , Pré-Escolar , Serviços de Saúde Comunitária/economia , Análise Custo-Benefício , Estudos Transversais , Cuba/epidemiologia , Custos de Cuidados de Saúde , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/educação , Humanos , Incidência , Meios de Comunicação de Massa , Prevalência , Atenção Primária à Saúde/economia , Prevenção Primária/economia , Prevenção Primária/educação , Avaliação de Programas e Projetos de Saúde , Recidiva , Sistema de Registros , Febre Reumática/complicações , Febre Reumática/economia , Febre Reumática/mortalidade , Cardiopatia Reumática/economia , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/mortalidade , Prevenção Secundária/economia , Prevenção Secundária/educação , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: to estimate the prevalence of coronary artery disease (CAD) in valvular heart disease of rheumatic (RVHD) and non-rheumatic (NVHD) etiology, assessing possible predictive factors for the presence of CAD. METHODS: This is a cross-sectional study of a series of cases obtained from a pre-defined population, wherein 1,412 patients referred for heart surgery of any etiology were evaluated. Of these, 294 primary heart disease patients aged > or =40 submitted to cinecoronary arteriography (CA) were identified and studied. RESULTS: patients with RVHD presented lower prevalence of CAD (4%) when compared to NVHD (33.61%), p<0.0001. The logistic regression analysis showed that age, typical angina-like chest pain (TACP), systemic arterial hypertension (SAH), diabetes and dyslipidemia were significantly related to CAD, and that the rheumatic etiology was not a disease determinant. Smoking and gender were clinically important in CAD, although not statistically significant. In the whole group, the Log-linear analysis showed that, regardless of the etiology, gender, age > or =55, SAH, TACP, diabetes and dyslipidemia were all related directly to CAD, with the latter three being the most important variables for the disease. CONCLUSION: the prevalence of CAD among RVHD patients is low, whereas it is high among NVHD patients; the rheumatic etiology does not seem to have any beneficial effects on the prevalence of CAD; gender, age, SAH, TACP, dyslipidemia and diabetes were identified as being strongly associated with the presence of CAD. It is possible to define the criteria that indicate the need for pre-surgical CA in heart valve replacements, so that the standard indication after the age of 40 years can be avoided.
Assuntos
Valva Aórtica , Doença da Artéria Coronariana/epidemiologia , Valva Mitral , Cardiopatia Reumática/epidemiologia , Adulto , Valva Aórtica/cirurgia , Brasil/epidemiologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/cirurgia , Estudos Transversais , Métodos Epidemiológicos , Feminino , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/cirurgia , Hospitais Públicos , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/epidemiologia , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Revascularização Miocárdica , Prevalência , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/cirurgiaRESUMO
OBJETIVO: Avaliar a prevalência de doença arterial coronariana (DAC) na valvopatia de etiologia reumática e não-reumática, examinando possíveis fatores preditivos da presença da doença. MÉTODOS: Estudo transversal, de série de casos obtidos em população pré-definida. Foram avaliados 1.412 pacientes com indicação de cirurgia cardíaca por qualquer etiologia. Destes, foram encontrados e estudados 294 casos com valvopatia primária de etiologias reumática e não-reumática, com idade > 40 anos, submetidos a coronariografia. RESULTADOS: Os valvopatas reumáticos apresentaram menor prevalência de DAC (4 por cento) que os não-reumáticos (33,61 por cento) (p < 0,0001). O modelo de regressão logística evidenciou que idade, dor torácica típica, hipertensão arterial sistêmica (HAS), diabete melito e dislipidemia estavam significativamente relacionados à DAC, e que a etiologia reumática não era determinante da doença. Tabagismo e sexo revelaram-se de importância clínica na DAC, embora sem significância estatística. No grupo total, o modelo de análise Log linear demonstrou que, independentemente da etiologia, sexo, idade > 55 anos, HAS, dor torácica típica, diabete e dislipidemia se relacionavam diretamente com a DAC, sendo as três últimas as variáveis de maior peso para a doença. CONCLUSÃO: A prevalência de DAC é baixa entre valvopatas reumáticos e mais alta entre não-reumáticos; a etiologia reumática não parece exercer efeito protetor sobre a prevalência de DAC; e as variáveis sexo, idade, HAS, dor torácica típica, dislipidemia e diabete melito foram identificadas como fortemente associadas à presença de DAC. É possível definir critérios de indicação de coronariografia pré-operatória nas trocas valvares, podendo-se evitar a indicação rotineira a partir dos 40 anos.
OBJECTIVE: to estimate the prevalence of coronary artery disease (CAD) in valvular heart disease of rheumatic (RVHD) and non-rheumatic (NVHD) etiology, assessing possible predictive factors for the presence of CAD. METHODS: This is a cross-sectional study of a series of cases obtained from a pre-defined population, wherein 1,412 patients referred for heart surgery of any etiology were evaluated. Of these, 294 primary heart disease patients aged >40 submitted to cinecoronary arteriography (CA) were identified and studied. RESULTS: patients with RVHD presented lower prevalence of CAD (4 percent) when compared to NVHD (33.61 percent), p<0.0001. The logistic regression analysis showed that age, typical angina-like chest pain (TACP), systemic arterial hypertension (SAH), diabetes and dyslipidemia were significantly related to CAD, and that the rheumatic etiology was not a disease determinant. Smoking and gender were clinically important in CAD, although not statistically significant. In the whole group, the Log-linear analysis showed that, regardless of the etiology, gender, age >55, SAH, TACP, diabetes and dyslipidemia were all related directly to CAD, with the latter three being the most important variables for the disease. CONCLUSION: the prevalence of CAD among RVHD patients is low, whereas it is high among NVHD patients; the rheumatic etiology does not seem to have any beneficial effects on the prevalence of CAD; gender, age, SAH, TACP, dyslipidemia and diabetes were identified as being strongly associated with the presence of CAD. It is possible to define the criteria that indicate the need for pre-surgical CA in heart valve replacements, so that the standard indication after the age of 40 years can be avoided.