Assuntos
Síndrome do QT Longo/complicações , Medicamentos sob Prescrição/efeitos adversos , Estresse Psicológico/complicações , Cardiomiopatia de Takotsubo/complicações , Torsades de Pointes/etiologia , Desequilíbrio Hidroeletrolítico/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Desfibriladores Implantáveis , Eletrólitos/metabolismo , Feminino , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/terapia , Magnésio/uso terapêutico , Potássio/uso terapêutico , Torsades de Pointes/tratamento farmacológico , Torsades de Pointes/terapiaRESUMO
BACKGROUND: Cardiovascular disease (CVD) occurs more frequently in individuals with a family history of premature CVD. Within families the demographics of CVD are poorly described. DESIGN: We examined the risk estimation based on the Systematic Coronary Risk Evaluation (SCORE) system and the Joint British Guidelines (JBG) for older unaffected siblings of patients with premature CVD (onset =55 years for men and =60 years for women). METHODS: Between August 1999 and November 2003 laboratory and demographic details were collected on probands with early-onset CVD and their older unaffected siblings. Siblings were screened for clinically overt CVD by a standard questionnaire and 12-lead electrocardiogram (ECG). RESULTS: A total of 790 siblings was identified and full demographic details were available for 645. The following siblings were excluded: 41 with known diabetes mellitus; seven with random plasma glucose of 11.1 mmol/l or greater; and eight with ischaemic ECG. Data were analysed for 589 siblings from 405 families. The mean age was 55.0 years, 43.1% were men and 28.7% were smokers. The mean total serum cholesterol was 5.8 mmol/l and hypertension was present in 49.4%. Using the SCORE system, when projected to age 60 years, 181 men (71.3%) and 67 women (20.0%) would be eligible for risk factor modification. Using JBG with a 10-year risk of 20% or greater, 42 men (16.5%) and four women (1.2%) would be targeted. CONCLUSIONS: Large numbers of these asymptomatic individuals meet both European and British guidelines for the primary prevention of CVD and should be targeted for risk factor modification. The prevalence of individuals defined as eligible for treatment is much higher when using the SCORE system.
Assuntos
Doenças Cardiovasculares/genética , Medição de Risco/métodos , Irmãos , Adulto , Doenças Cardiovasculares/epidemiologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
A 67 year old man presented with new-onset atrial flutter. He had a history of coronary artery bypass graft (CABG) surgery on two occasions. Subsequent investigation revealed the presence of a large saphenous vein graft (SVG) aneurysm compressing the right heart. We postulate that the SVG aneurysm was the precipitating cause for the atrial flutter. This case is the first in the literature to document an atrial arrhythmia as the presenting feature of a SVG aneurysm.
Assuntos
Flutter Atrial/etiologia , Aneurisma Coronário/diagnóstico , Aneurisma Coronário/etiologia , Ponte de Artéria Coronária/efeitos adversos , Veia Safena/transplante , Idoso , Diagnóstico Diferencial , Ecocardiografia Transesofagiana , Eletrocardiografia , Humanos , MasculinoRESUMO
BACKGROUND: Ischaemic heart disease (IHD) is a complex disease due to the combination of environmental and genetic factors. Mutations in the MEF2A gene have recently been reported in patients with IHD. In particular, a 21 base pair deletion (Delta7aa) in the MEF2A gene was identified in a family with an autosomal dominant pattern of inheritance of IHD. We investigated this region of the MEF2A gene using an Irish family-based study, where affected individuals had early-onset IHD. METHODS: A total of 1494 individuals from 580 families were included (800 discordant sib-pairs and 64 parent-child trios). The Delta7aa region of the MEF2A gene was investigated based on amplicon size. RESULTS: The Delta7aa mutation was not detected in any individual. Variation in the number of CAG (glutamate) and CCG (proline) residues was detected in a nearby region. However, this was not found to be associated with IHD. CONCLUSION: The Delta7aa mutation was not detected in any individual within the study population and is unlikely to play a significant role in the development of IHD in Ireland. Using family-based tests of association the number of tri-nucleotide repeats in a nearby region of the MEF2A gene was not associated with IHD in our study group.
Assuntos
Proteínas de Domínio MADS/genética , Mutação , Isquemia Miocárdica/genética , Fatores de Regulação Miogênica/genética , Fatores Etários , Feminino , Humanos , Fatores de Transcrição MEF2 , Masculino , Pessoa de Meia-Idade , Irlanda do Norte , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Ischemic heart disease (IHD), the leading cause of death worldwide, is a multifactorial disease arising from the complex interplay of genetic and environmental factors. There is considerable evidence that nitric oxide (NO) plays an important role in protecting against atherosclerosis, the process underlying IHD. Endothelial NO is synthesized from the amino acid l-arginine by the endothelial isoform of NO synthase (eNOS). Thus, polymorphisms of the eNOS gene, by altering production of NO within the vascular endothelium, are potential risk factors for IHD. Several groups have investigated the role of the G894T polymorphism of the eNOS gene in IHD by using case-control association studies; however, its role is unclear because of contradictory results from these studies. We applied family-based association tests to investigate the role of this polymorphism in IHD in a well-defined Irish population. METHODS: A total of 1023 individuals from 388 families (discordant sibships and parent-offspring trios) were recruited. Linkage disequilibrium between the polymorphism and IHD was tested for by using the combined transmission disequilibrium test/sib-transmission disequilibrium test and pedigree disequilibrium test. RESULTS: Both the combined transmission disequilibrium test/sib-transmission disequilibrium test and pedigree disequilibrium test analyses found no statistically significant excess transmission of either allele to affected individuals (P = .57 and P = .38, respectively). CONCLUSIONS: Using robust family-based association tests specifically designed for the study of complex diseases, we found no evidence that the G894T polymorphism of the eNOS gene has a significant role in the development of IHD in our population.
Assuntos
Isquemia Miocárdica/genética , Óxido Nítrico Sintase/genética , Polimorfismo Genético , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Isquemia Miocárdica/enzimologia , Óxido Nítrico Sintase Tipo III , LinhagemRESUMO
Atherosclerosis has an inflammatory basis, with cytokines, cellular adhesion molecules and pro-inflammatory cells having important roles in the initiation and progression of this process. Interleukin (IL) 6, IL-10 and transforming growth factor (TGF) beta1 have been proposed as important modulators of the atherosclerotic process, with IL-6 having a pro-inflammatory, atherogenic effect and IL-10 and TGF-beta1 having anti-inflammatory, protective roles. The possible role of functional polymorphisms in the promoter regions of the IL-6, IL-10 and TGF-beta1 genes in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. We genotyped 1,012 individuals from 386 families with at least one member prematurely affected with IHD. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test, no association between any of the IL-6 -174G/C, IL-10 -1082G/A and TGF-beta1 -509C/T polymorphisms and IHD was found. Our data demonstrate that, in an Irish population, these polymorphisms are not associated with IHD.
Assuntos
Citocinas/genética , Isquemia Miocárdica/genética , Polimorfismo Genético , Citocinas/metabolismo , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/metabolismoRESUMO
Matrix metalloproteinase-3 (MMP-3) has been proposed as an important mediator of the atherosclerotic process. The possible role of the functional -1612 5A/6A polymorphism of the MMP-3 gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the MMP-3 -1612 5A/6A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MMP-3 -1612 5A/6A polymorphism is not associated with IHD.
Assuntos
Cardiopatias/genética , Metaloproteinase 3 da Matriz/genética , Isquemia Miocárdica/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Adulto , Idade de Início , Alelos , Saúde da Família , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Irlanda , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Fatores de Risco , Análise de Sequência de DNARESUMO
BACKGROUND: Elevated homocysteine is associated with ischaemic heart disease (IHD). The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene results in reduced MTHFR enzyme activity and reduced methylation of homocysteine to methionine resulting in mild hyperhomocysteinaemia. Case-control association studies of the role of the C677T MTHFR polymorphism in IHD have produced conflicting results. We therefore used newly described family-based association tests to investigate the role of this polymorphism in IHD, in a well-defined population. METHODS: A total of 352 individuals from 129 families (discordant sibships and parent-child trios) were recruited. Linkage disequilibrium between the polymorphism and IHD was tested for using the combined transmission disequilibrium test (TDT)/sib-TDT and pedigree disequilibrium test (PDT). Homocysteine levels were measured. RESULTS: Both the TDT/sib-TDT and PDT analyses found a significantly reduced transmission of the T allele to affected individuals (P=0.016 and P=0.021). There was no significant difference in homocysteine levels between affected and unaffected siblings. TT homozygotes had mean homocysteine levels significantly higher than those of TC heterozygotes (P<0.001) and CC homozygotes (P<0.001). CONCLUSIONS: These data suggest that in contrast to the conventional hypothesis the T allele may be protective against IHD, independent of homocysteine levels.