RESUMO
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.
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Doença das Coronárias/embriologia , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Estudos de Casos e Controles , Fatores de Risco , JejumRESUMO
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 (pË0.001).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.
Assuntos
Doença das Coronárias , Hiper-Homocisteinemia , Adulto , Estudos de Casos e Controles , Doença das Coronárias/epidemiologia , Jejum , Humanos , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
AIM: Hyperhomocysteinemia has been associated with different pathologies, including cardiovascular diseases, hypertension, diabetes, and breast cancer (BC). To examine the differences in total homocysteine (tHcy) plasma levels, we compared healthy women to BC patients from a Mexican population. MATERIALS AND METHODS: The tHcy plasma levels were measured using high-performance liquid chromatography with a fluorescence detector in 89 female controls and 261 BC patients. RESULTS: The observed plasma tHcy levels were significantly higher among the BC patients (11.1019 ± 5.9161 µmol/l) compared to the controls (9.1046 ± 1.3213 µmol/l) (p = 0.002), and these differences were evident when stratified by age (≥ 50 years old), menopause status, overweight and obesity, miscarriages, node metastases, progression, subtype classification (luminal, Her2 and triple negative) and nonresponse to chemotherapy. CONCLUSIONS: The tHcy plasma levels could be a good marker for the progression and chemosensitivity of BC in the analyzed sample from a Mexican population.
Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/epidemiologia , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Comorbidade , Feminino , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/diagnóstico , México/epidemiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Vigilância da População , Fatores de Risco , Avaliação de SintomasRESUMO
BACKGROUND: The aim of this study was to evaluate the OpenArray platform for genetic testing of blood donors and to assess the genotype frequencies of nucleotide-polymorphisms (SNPs) associated with venous thrombosis (G1691A and G20210A), hyperhomocysteinemia (C677T, A1298C), and hereditary hemochromatosis (C282Y, H63D and S65C) in blood donors from Sao Paulo, Brazil. METHODS: We examined 400 blood donor samples collected from October to November 2011. The SNPs were detected using OpenArray technology. The blood samples were also examined using a real-time PCR-FRET system to compare the results and determine the accuracy of the OpenArray method. RESULTS: We observed 100% agreement in all assays tested, except HFE C282Y, which showed 99.75% agreement. The HFE C282Y assay was further confirmed through direct sequencing, and the results showed that OpenArray analysis was accurate. The calculated frequencies of each SNP were FV G1691A 98.8% (G/G), 1.2% (G/A); FII G2021A 99.5% (G/G), 0.5% (G/A); MTHFR C677T 45.5% (C/C), 44.8% (C/T), 9.8% (T/T); MTHFR A1298C 60.3% (A/A), 33.6% (A/C), 6.1% (C/C); HFE C282Y 96%(G/G), 4%(G/A), HFE H63D 78.1%(C/C), 20.3% (C/G), 1.6% (G/G); and HFE S65C 98.1% (A/A), 1.9% (A/T). CONCLUSION: Taken together, these results describe the frequencies of SNPs associated with diseases and are important to enhance our current knowledge of the genetic profiles of Brazilian blood donors, although a larger study is needed for a more accurate determination of the frequency of the alleles. Furthermore, the OpenArray platform showed a high concordance rate with standard FRET RT-PCR.
Assuntos
Doadores de Sangue , Hemocromatose/genética , Hiper-Homocisteinemia/genética , Polimorfismo de Nucleotídeo Único , Trombose Venosa/genética , Adulto , Alelos , Brasil , Fator V/genética , Feminino , Expressão Gênica , Frequência do Gene , Testes Genéticos , Genótipo , Hemocromatose/diagnóstico , Proteína da Hemocromatose , Ensaios de Triagem em Larga Escala , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Hiper-Homocisteinemia/diagnóstico , Masculino , Proteínas de Membrana/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Protrombina/genética , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: Hyperhomocysteinemia (Hhcy) is considered an independent risk factor for vascular diseases and, more recently, for dementia. The methionine loading test (MLT) is useful for diagnosing additional subjects with moderate Hhcy. However, it is a complex and time-consuming procedure. A noninvasive test for the diagnosis of moderate Hhcy is desirable. METHODS: The study protocol consisted of three consecutive visits. During the first visit, we performed an MLT to characterize the Hhcy status of 75 healthy adult subjects. For the breath test protocol, we selected a subsample and assigned to the control group 17 subjects with fasting and post-loading homocysteine (Hcy) ≤12 and <42.3 µmol/L, respectively, and to the Hhcy group 16 subjects with fasting Hcy ≤12 and >42.3 µmol/L after loading. Selected subjects were requested to have a second visit to perform a breath test within 1-4 weeks following the MLT test and received an oral dose of 2.5 mg/kg of 1-13C-methionine dissolved in water. Breath samples were collected at basal, 20, 40, 60, 80, 100 and 120 min (test 1). The same procedure was repeated within 1 week (test 2). RESULTS: MLT was useful for diagnosing almost twice the number of individuals with Hhcy (24%) in comparison with the fasting determination alone (13.3%). The 13C-methionine breath test reported a sensitivity of 81.3% and a specificity of 64.7% against the MLT. The coefficient of variation between breath test 1 and breath test 2 was 9.0±5.4%. CONCLUSIONS: The 13C-methionine breath test is a valid and reliable method for identifying subjects with moderate Hhcy.
Assuntos
Hiper-Homocisteinemia/diagnóstico , Metionina/análise , Adulto , Área Sob a Curva , Índice de Massa Corporal , Testes Respiratórios , Isótopos de Carbono/química , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Curva ROC , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Hyperhomocysteinemia is a prothrombotic risk factor. Homocysteine is evaluated during fasting and after an oral methionine load (OML). AIM: To determine the safety of the OML test according to the general performance status and clinical laboratory tests. We studied healthy nonsmoking volunteers and patients with several thrombotic conditions. Before and after receiving an OML, blood samples were obtained to perform several laboratory tests. We also evaluated acute and subacute adverse effects and 30-day associated morbidity and mortality. Of 353 individuals, three were eliminated because they did not tolerate the OML. We studied 175 healthy individuals and 175 patients without age differences. After OML, mild to moderate clinical abnormalities were recorded in 78 subjects (22.1%): nausea (n = 69; 88.5%), dizziness (n = 13; 16.7%) and decreased or increased blood pressure (n = 8; 10.2%). Nausea always disappeared after breakfast in affected individuals. Prevalence of complications was similar in patients and controls. No patient required hospitalization and there was no mortality during the 30-day study period. In conclusion, OML test had no significant undesirable effects on the clinical status or the general laboratory tests of patients and healthy controls. Some mild and moderate symptoms associated with OML tests were observed, and OML test did not negatively affect general laboratory tests. OML test is a safe diagnostic procedure in patients with previous thrombotic events (and with the consequent associated risk factors such as diabetes mellitus or dyslipidemia) and in healthy subjects.
Assuntos
Hiper-Homocisteinemia/diagnóstico , Metionina , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Laboratório Clínico/normas , Feminino , Humanos , Estudos Longitudinais , Masculino , Metionina/administração & dosagem , Metionina/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVES: To quantify serum butyrylcholinesterase activity in haemodialysis patients and to evaluate if the homocysteine levels and/or oxidative stress biomarkers have an effect on butyrylcholinesterase. MATERIALS AND METHODS: Blood samples were collected from patients and healthy subjects (control). The plasma homocysteine and TBARS levels; serum butyrylcholinesterase activity; blood delta aminolevulinic acid dehydratase (ALA-D) activity and methahaemoglobin were analyzed. The mortality of the patients was also evaluated after 3 years. RESULTS: The homocysteine was increased and butyrylcholinesterase decreased compared to control (p<0.05). TBARS and methahaemoglobin were increased and ALA-D decreased (p<0.05). The following correlations were found: homocysteine with butyrylcholinesterase (-0.44); methahaemoglobin (0.41); ALA-D (-0.68); and TBARS (0.66). The partial correlation between homocysteine with butyrylcholinesterase, withdrawn the effect of TBARS, was -0.30; all p<0.05. Moreover, it was observed that 22% of the patients died due to cardiovascular problems. CONCLUSION: Thus, our findings support a direct association between the reduction of butyrylcholinesterase by the increase of homocysteine and an indirect effect by increase in oxidative stress.
Assuntos
Butirilcolinesterase/metabolismo , Regulação para Baixo/fisiologia , Hiper-Homocisteinemia/enzimologia , Estresse Oxidativo/fisiologia , Diálise Renal , Adulto , Idoso , Ativação Enzimática/fisiologia , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversosRESUMO
BACKGROUND: Patients with inflammatory bowel disease have an increased risk of thrombosis. Hyperhomocysteinemia is one of the factors that have been related to thromboembolic complications. Patients with hyperhomocysteinemia and normal fasting homocysteine levels can be identified with an oral methionine load. We studied homocysteine levels in patients with IBD during fasting and after methionine load to determine the true prevalence of hyperhomocysteinemia and its relation with thrombotic events. METHODS: Prospective analysis of homocysteine levels in consecutive patients with IBD during fasting and 6-8 hours after an oral methionine load. Levels of folate and vitamin B12 were also determined. History of thrombotic events were recorded. RESULTS: Eighty-two patients with IBD, 56 with UC and 26 with CD were included. Eighteen patients (22%) had hyperhomocysteinemia during fasting. Mean levels of homocysteine after methionine load were 20.4 +/- 18.1 micromol/l (range, 1-79.7 micromol/l), and 43 patients (52%) had hyperhomocysteinemia (> or =20 micromol/l) after methionine load. Six patients (7.3%) had history of thrombosis. The homocysteine levels during fasting and after methionine load were significantly higher in patients with thrombotic events than in patients without thrombosis (15.5 +/- 3.7 micromol/l vs. 6.6 +/- 6.5 micromol/l; P = 0.002; 44.5 +/- 20.9 micromol/l vs. 18.4 +/- 16.5 micromol/l; P < 0.001, respectively). CONCLUSIONS: There is a higher prevalence of hyperhomocysteinemia in IBD patients than previously thought, this can be identified with an oral challenge of a methionine load. Hyperhomocysteinemia increases the risk of thromboembolic complications in patients with IBD.
Assuntos
Homocisteína/sangue , Hiper-Homocisteinemia/diagnóstico , Doenças Inflamatórias Intestinais/complicações , Metionina , Trombose/etiologia , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/epidemiologia , Incidência , Doenças Inflamatórias Intestinais/sangue , Masculino , Metionina/administração & dosagem , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Trombose/sangue , Trombose/epidemiologia , Vitamina B 12/sangueRESUMO
BACKGROUND: Hyperhomocysteinemia is considered an independent risk factor for vascular occlusive diseases. To date, there is no general agreement on hyperhomocysteinemia cutoff values. METHODS: To establish a homocysteine cutoff value, we performed a case-control study in 118 patients suffering from venous thrombosis and in 115 healthy subjects. We calculated odds ratios at different cutoff points and considered hyperhomocysteinemia as homocysteine levels above which the risk of venous thrombosis was increased. RESULTS: Initially we used the 97.5th percentiles for fasting homocysteine levels in the control group to calculate odds ratios (95% CI) of 9.5 (2.6-35.3), 3.7 (0.8-17.9) and 4.5 (1.7-123.8) for the total population, women and men, respectively. When individuals with well-known thrombotic risk factors were excluded (selected population), odds ratios were 10.5 (2.7- 41.1), 6.5 (1.3-32.1) and 11.2 (1.2-103.1), respectively, confirming hyperhomocysteinemia as an independent risk factor for venous thrombosis. We did not find any association of venous thrombosis with the homozygous methylenetetrahydrofolate reductase C677T mutation. When the hyperhomocysteinemia cutoff was set at other arbitrary points, odds ratios for the selected population were statistically significant only at >12 micromol/L. CONCLUSIONS: Based on our results, we propose 12 micromol/L as the hyperhomocysteinemia cutoff value.