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.

Three different presentation of same pathophysiology

We report three male patients of younger age group presented with acute vein thrombosis of different sites, right lower limb, cortical venous sinuses thrombosis with cerebral vascular accident and third case is mesenteric vein thrombosis. All patients were Vegetarian, had low level of cobalamin with marked hyper homocysteinemia with normal serum and red cell folic acid. The low Cobalamin level was not suspected secondary to pernicious anemia, based on the fact that there was no evidence of atrophic gastritis and an absence of antiparietal cell antibodies. There were no evident of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, and hormone replacement therapy. No deficiencies in protein C, protein S, or antithrombin III, normal factor V Leiden, no prothrombin gene mutation 20210A and no clone for paroxysmal nocturnal hemoglobinurea were detected, no cause was found for the thrombosis apart from their secondary hyperhomocysteinemia

Cortical venous thrombosis due to acquired hyperhomocysteinaemia.

A 20-year-old student presented with generalized tonic– clonic seizures and was diagnosed to have cortical venous thrombosis. Her dietary history and the clinical signs of vitamin deficiency prompted further investigations, which detected hyperhomocysteinaemia secondary to vitamin B12 deficiency as a factor contributing to the hypercoagulable state. This case highlights the importance of a balanced diet, as well as the necessity for primordial prevention.

Serum homocysteine in indian adolescents.

Objective. To assay serum homocysteine levels and examine its association with conventional risk factors for cardiovascular disease (CVD) in Indian adolescents. Methods. This was a cross-sectional study conducted in tertiary care hospital in northern India in apparently healthy adolescents aged 10 – 19 yr. A pre-designed questionnaire was used to assess conventional risk factors. Serum homocysteine levels of ≥ 12μmol/L, serum triglycerides ≥ 150 mg% and serum cholesterol ≥ 200 mg% were taken as hyperhomocysteinemia, hypertriglyceridemia and hypercholesterolemia, respectively. Serum high-density lipoprotein (HDL) ≥ 40 mg% was considered protective for CVD. Results. In 103 subjects, 36.87 % females, mean serum homocysteine level was 11.649 ±0.416μmol/L. Hyperhomocysteinemia was present in 46 (44.6%, 95% CI: 34.965-54.75) subjects. Dietary deficiency of vitamin B12 and folic acid, body mass index (BMI) > 84th percentile and altered lipid profile were associated with hyperhomocysteinemia on univariate analysis. After multivariate adjustment for BMI and vegetarian diet, low serum HDL (OR: 23.81, 95% CI: 2.86-200; p =0.003) and serum hypertriglyceridemia (OR: 4.17, 95% CI: 1.51 – 13.51; p = 0.022) had independent association with hyperhomocysteinemia. Conclusion. Since we have also found an association between hyperhomocysteinemia and low serum HDL levels and hypertriglyceridemia, which are conventional risk factors for CVD, interventional strategies are urgently needed among adolescents for prevention of CVD.

Hyperhomocysteinemia and bone mineral density: a case - control study

To find out whether homocysteine has a direct effect on bone or it is an innocent bystander? The study was designed to investigate probable role of homocysteine on bone mineral density [BMD]. This a case-control study wherein, 30 patients with at Least one densitometry criterion of osteoporosis in femoral neck or Lumbar spine were enrolled as the case group along with another 30 normal subjects with normal BMD, as the control group. The patients of the two groups were matched for their ages and sex. In all eligible patients BMD was measured by DEXA and fasting serum homocysteine level were measured by Enzyme Immunoassay Kit. The mean of serum level of homocysteine were 11.67 +/- 4.38 and 11.97 +/- 3.09 imol/l in control and case groups respectively. The difference between two groups was not significant [P=0.761]. Serum homocysteine level and BMC of various areas in case and control groups had no significant correlation [lumbar spine in control group [r= 0.025, p=0.9], lumbar spine in case group [r=0.071, p=0.716], femoral neck in control group [r=0.276, p=0.147], femoral neck in case group [r=0.001, p=0.998fl. Despite numerous studies about direct effect of homocysteine on increase of osteoporotic fracture risk, our study did not show a correlation between serum Level of homocysteine and BMD. Due to multiplicity of factors affecting bone density, final conclusions need extensive investigations with attention to other confounding factors

Plasma homocysteine levels and vitamin B status in patients with pseudoexfoliation syndrome

To determine and compare the plasma levels of homocysteine and vitamin B [B6, B12 and folate] in patients with Pseudoexfoliation syndrome [PEXS], pseudoexfoliation glaucoma [PEXG], retinal vein occlusion with pseudoexfoliation [PEX+RVO] and in normal individuals. The current study was conducted in the Third Eye Clinic, Ankara Numune Training and Research Hospital, Turkey, between August 2004 and February 2005. Twenty cases with PEXS [Group 1], 20 cases with PEXG [Group 2], 16 cases with PEX+RVO [central or branch retinal vein occlusion] [Group 3] and 20 normal individuals [control group] were included in the study. Those who use vitamin supplements or drugs affecting the plasma homocysteine levels were excluded from the study. Plasma homocysteine levels were 17.6 +/- 4.4 mmol/l in Group 1, 18.5 +/- 4.5 mmol/l in Group 2, 22.2 +/- 6.0 mmol/l in Group 3, and 14.0 +/- 3.1 mmol/l in the control group. It was highest in Group 3 [p<0.001]. The ratio of hyperhomocysteinemia was calculated as 35% [Group 1], 45% [Group 2], 68.7% [Groups 3] and 15% [control]. These values were statistically higher in the groups with PEXS than in the control group [p=0.009]. We did not find any statistically significant difference between the groups with respect to the levels of vitamin B6 and B12 [p>0.05], but the level of folate was lowest in Group 3 [p<0.001]. Hyperhomocysteinemia is a risk factor for thromboembolic vasculopathy in patients with PEXS and PEXG. Therefore, vitamin B supplementation should be considered in these patients when hyperhomocysteinemia is detected

Young man presenting with chest pain

This is a case report of a young man, who had an acute coronary event followed by angioplasty. On further workup he was found out to have hyper-homocysteinemia

Hyperhomocysteinemia masquerading as pulmonary embolism.

We describe a 30-year-old male who presented with acute onset of breathlessness, tachycardia, and palpitations associated with distension of jugular vein and clear lungs on physical examination. The chest X-ray was normal and ECG was showing S1Q3T3 and right ventricular strain pattern. His 2-D echocardiography was showing dilated right atrium, right ventricular dilatation and moderate pulmonary arterial hypertension. He was found to have thrombosis involving left side of deep venous system with normal superficial venous system (Doppler proved). All routine blood investigations for etiology of recurrent DVT were normal except serum homocyteine level, which was significantly raised. Megaloblastic anemia on peripheral smear and hyperhomocysteinemia prompted us to search for its cause, which was subsequently found to be vitamin B12 deficiency. Such an association of megaloblastic anemia due to vitamin B12 deficiency leading to hyperhomocysteinemia and subsequent thrombosis in left venous system presenting as acute pulmonary embolism has not been described earlier in the medical literature.

Hiperhomocisteinemia e estresse oxidativo na insuficiência renal crônica: efeitos da suplementaçäo de ácido fólico em pacientes sob hemodiálise / Hyperhomocysteinemia and oxidative stress in the chronic renal insufficience: effect of the supplementation of folic acid in patients under hemodialysis

A maior parte dos pacientes em tratamento de diálise, hemodiálise (HD) ou diálise peritoneal (CAPD), apresentam concentrações plasmáticas elevadas do aminoácido homocisteína, quadro que pode contribuir para a criação de um estresse oxidativo crônico nesse grupo. A presença conjunta de hiperhomocisteinemia e estresse oxidativo pode ser fator determinante no aparecimento de alterações vasculares e doenças cardíacas, sendo esta a principal causa de morte entre pacientes em diálise. Com o intuito de avaliar a hiperhomocisteinemia e estresse oxidativo em pacientes sob diálise e suas interrelações, foram utilizadas duas suplementações distintas de ácido fólico e seus efeitos sob o controle da hiperhomocisteinemia e alterações no quadro pró e antioxidante foram acompanhados em um grupo de pacientes sob hemodiálise em três momentos: basal (B), após a primeira (S1) e após a segunda suplementação (S2)...