Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors / Hiper-homocisteinemia como fator de risco independente para doença coronariana: comparação com fatores de risco convencionais

The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p˂0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor [...].

O presente estudo foi desenhado para avaliar a força da associação da concentração elevada de homocisteína no plasma como um fator de risco para doença cardíaca coronária independente do fator de risco convencional. Foi um estudo de caso-controle realizado no Punjab Institute of Cardiology Lahore. Um total de 210 indivíduos com idade entre 25 e 60 anos, compreendendo 105 pacientes recém-admitidos de CHD como casos e 105 indivíduos saudáveis pareados por idade e sexo sem histórico de CHD como controle, foi recrutado para o estudo. Amostras de sangue em jejum foram obtidas de casos e controles. A homocisteína plasmática foi analisada pelo método de imunoensaio de polarização de fluorescência (FPIA) em analisador de imunoensaio automatizado (Abbott IMX). Colesterol total, triglicerídeos e colesterol HDL foram analisados usando métodos de kit calorimétrico. A concentração de colesterol LDL foi calculada pela fórmula de Friedewald. Os pacientes também foram avaliados para fatores de risco tradicionais, como idade, sexo, história familiar de DCV, hipertensão, tabagismo e atividade física, e foram comparados com indivíduos de controle. Os dados coletados foram inseridos no SPSS versão 24 para análise e interpretação. A média de idade nos grupos controles e experimentais foi de 43,00 ± 8,42 anos e 44,72 ± 8,59 anos com distribuição estatisticamente igual (p-valor = 0,144). A homocisteína plasmática média para os casos foi de 22,33 ± 9,22 µmol / L, enquanto no grupo controle foi de 12,59 ± 3,73 µmol / L. Diferença altamente significativa foi observada entre o nível plasmático médio de homocisteína em casos e controles (p ˂ 0,001). A regressão logística simples indica uma forte associação de doença cardíaca coronária com hiper-homocisteinemia (OR 7,45), que permaneceu significativamente associada com doença cardíaca coronária por multivariada regressão logística (OR 7,10, 95% C1 3,12-12,83, p = 0,000). O presente estudo conclui [...].

Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors

Abstract The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor for coronary heart disease independent of conventional risk factors and can be used as an indicator for predicting the future possibility for the onset of CVD.

Resumo O presente estudo foi desenhado para avaliar a força da associação da concentração elevada de homocisteína no plasma como um fator de risco para doença cardíaca coronária independente do fator de risco convencional. Foi um estudo de caso-controle realizado no Punjab Institute of Cardiology Lahore. Um total de 210 indivíduos com idade entre 25 e 60 anos, compreendendo 105 pacientes recém-admitidos de CHD como casos e 105 indivíduos saudáveis pareados por idade e sexo sem histórico de CHD como controle, foi recrutado para o estudo. Amostras de sangue em jejum foram obtidas de casos e controles. A homocisteína plasmática foi analisada pelo método de imunoensaio de polarização de fluorescência (FPIA) em analisador de imunoensaio automatizado (Abbott IMX). Colesterol total, triglicerídeos e colesterol HDL foram analisados usando métodos de kit calorimétrico. A concentração de colesterol LDL foi calculada pela fórmula de Friedewald. Os pacientes também foram avaliados para fatores de risco tradicionais, como idade, sexo, história familiar de DCV, hipertensão, tabagismo e atividade física, e foram comparados com indivíduos de controle. Os dados coletados foram inseridos no SPSS versão 24 para análise e interpretação. A média de idade nos grupos controles e experimentais foi de 43,00 ± 8,42 anos e 44,72 ± 8,59 anos com distribuição estatisticamente igual (p-valor = 0,144). A homocisteína plasmática média para os casos foi de 22,33 ± 9,22 µmol / L, enquanto no grupo controle foi de 12,59 ± 3,73 µmol / L. Diferença altamente significativa foi observada entre o nível plasmático médio de homocisteína em casos e controles (p 0,001). A regressão logística simples indica uma forte associação de doença cardíaca coronária com hiper-homocisteinemia (OR 7,45), que permaneceu significativamente associada com doença cardíaca coronária por multivariada regressão logística (OR 7,10, 95% C1 3,12-12,83, p = 0,000). O presente estudo conclui que níveis elevados de homocisteína plasmática são fator de risco independente para doença cardíaca coronária, independentemente dos fatores de risco convencionais, e pode ser usado como um indicador para prever a possibilidade futura de aparecimento de DCV.

Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors / Hiper-homocisteinemia como fator de risco independente para doença coronariana: comparação com fatores de risco convencionais

Abstract The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p˂0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor for coronary heart disease independent of conventional risk factors and can be used as an indicator for predicting the future possibility for the onset of CVD.

Resumo O presente estudo foi desenhado para avaliar a força da associação da concentração elevada de homocisteína no plasma como um fator de risco para doença cardíaca coronária independente do fator de risco convencional. Foi um estudo de caso-controle realizado no Punjab Institute of Cardiology Lahore. Um total de 210 indivíduos com idade entre 25 e 60 anos, compreendendo 105 pacientes recém-admitidos de CHD como casos e 105 indivíduos saudáveis ​​pareados por idade e sexo sem histórico de CHD como controle, foi recrutado para o estudo. Amostras de sangue em jejum foram obtidas de casos e controles. A homocisteína plasmática foi analisada pelo método de imunoensaio de polarização de fluorescência (FPIA) em analisador de imunoensaio automatizado (Abbott IMX). Colesterol total, triglicerídeos e colesterol HDL foram analisados ​​usando métodos de kit calorimétrico. A concentração de colesterol LDL foi calculada pela fórmula de Friedewald. Os pacientes também foram avaliados para fatores de risco tradicionais, como idade, sexo, história familiar de DCV, hipertensão, tabagismo e atividade física, e foram comparados com indivíduos de controle. Os dados coletados foram inseridos no SPSS versão 24 para análise e interpretação. A média de idade nos grupos controles e experimentais foi de 43,00 ± 8,42 anos e 44,72 ± 8,59 anos com distribuição estatisticamente igual (p-valor = 0,144). A homocisteína plasmática média para os casos foi de 22,33 ± 9,22 µmol / L, enquanto no grupo controle foi de 12,59 ± 3,73 µmol / L. Diferença altamente significativa foi observada entre o nível plasmático médio de homocisteína em casos e controles (p ˂ 0,001). A regressão logística simples indica uma forte associação de doença cardíaca coronária com hiper-homocisteinemia (OR 7,45), que permaneceu significativamente associada com doença cardíaca coronária por multivariada regressão logística (OR 7,10, 95% C1 3,12-12,83, p = 0,000). O presente estudo conclui que níveis elevados de homocisteína plasmática são fator de risco independente para doença cardíaca coronária, independentemente dos fatores de risco convencionais, e pode ser usado como um indicador para prever a possibilidade futura de aparecimento de DCV.

Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors.

The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p˂0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor for coronary heart disease independent of conventional risk factors and can be used as an indicator for predicting the future possibility for the onset of CVD.

Combinatorial association and abundance of components of interferon-stimulated gene factor 3 dictate the selectivity of interferon responses.

Genes containing the interferon-stimulated response element (ISRE) enhancer have been characterized as transcriptionally responsive primarily to type I interferons (IFN alpha/beta). Induction is due to activation of a multimeric transcription factor, interferon-stimulated gene factor 3 (ISGF3), which is activated by IFN alpha/beta but not by IFN gamma. We found that ISRE-containing genes were induced by IFN gamma as well as by IFN alpha in Vero cells. The IFN gamma response was dependent on the ISRE and was accentuated by preexposure of cells to IFN alpha, a treatment that increases the abundance of ISGF3 components. Overexpression of ISGF3 polypeptides showed that the IFN gamma response depended on the DNA-binding protein ISGF3 gamma (p48) as well as on the 91-kDa protein STAT91 (Stat1 alpha). The transcriptional response to IFN alpha required the 113-kDa protein STAT113 (Stat2) in addition to STAT91 and p48. Mutant fibrosarcoma cells deficient in each component of ISGF3 were used to confirm that IFN gamma induction of an ISRE reporter required p48 and STAT91, but not STAT113. A complex containing p48 and phosphorylated STAT91 but lacking STAT113 bound the ISRE in vitro. IFN gamma-induced activation of this complex, preferentially formed at high concentrations of p48 and STAT91, may explain some of the overlapping responses to IFN alpha and IFN gamma.

Nerve growth factor production by lymphocytes.

Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of peripheral sympathetic neurons and basal forebrain cholinergic neurons. Recently, NGF has also been shown to have effects on cells of the immune system. In a search for extra neural sources of NGF, we detected NGF-specific mRNA in mouse T lymphocytes of both the CD4+ and CD8+ phenotypes with the use of an RNase protection assay, PCR, and DNA sequence analysis. In CD4+ cells, NGF was present in both Th1 and Th2 Ag-specific clones, but an increase of NGF-specific message was detected after antigenic stimulation only in Th2 clones. NGF mRNA was also detected in splenic B lymphocytes and in a cell line derived from a murine follicular center cell lymphoma. Translation into protein and secretion of NGF were demonstrated by Western blot analysis. The secreted NGF is in an active form capable of inducing differentiation of PC12 cells into sympathetic-like neurons. Furthermore, conditioned medium from clones or lines positive for NGF mRNA was capable of inducing p140 tyrosine kinase autophosphorylation in 3T3 fibroblasts transfected with cDNA encoding for the tyrosine kinase family NGF receptor. We conclude that lymphocytes synthesize and secrete NGF either as a para-autocrine factor acting on the immune system itself, or as a factor for the maintenance of peripheral neurons.