11 research outputs found
Blood levels of homocysteine, folate, vitamin B-6 and B-12 in women using oral contraceptives compared to non-users
Background and objectives: To compare the levels of total homocysteine (tHcy), folate, vitamin B-6 and B-12, in women not using oral contraceptives (OC) vs. those using OC. Materials and methods: 219 healthy women were enrolled in the study; 159 of them had not been using OC for at least 12 months prior to their enrolment, while 60 were on regular OC treatment. Results: The median levels of vitamin B-6 and B-12 were significantly lower in OC users than in non-users (24.2 vs. 32.9 nmol/l, p = 0.029; 278 vs. 429 ng/ml, p < 0.001). There were no statistically significant differences in the levels of tHcy (fasting and post-methionine loading) and folate. Conclusions: In our cross-sectional study, OC use was associated with low vitamin B-6 and B-12 levels. Since low vitamin B-6 levels are independently associated with heightened risks for arterial and venous thromboembolism (TE), they could partly account for the increased TE risk of OC users
Determination of total homocysteine in plasma: comparison of the Abbott Imx immunoassay with high performance liquid chromatography
Background and Objectives. The aim of this study was to compare the performance of a commercially available IMx immunoassay with that of a reversed-phase high performance liquid chromatography (HPLC) method for measuring plasma total homocysteine (tHcy). Methods. The levels of tHcy before and after oral methionine loading (ML) were measured in 135 healthy subjects and 39 patients scheduled for routine tHcy determination. The IMx method uses fluorescence polarization immunoassay (FPIA) technology. The HPLC-method includes derivatization with ABD-F and post-column fluorescence detection. Results. The imprecision was very low with both methods for both normal (11 μmol/L) and high (29 μmol/L) tHcy levels. The within and between-run coefficients of variation were < 5%. Both methods were able to discriminate between similar concentrations of tHcy both at normal and moderately high levels. There was a good correlation between measurements obtained with the two methods (r = 0.985, p = 0.001). The mean levels of tHcy measured with the IMx assay tended to be slightly higher than those with the HPLC both in the fasting state (mean difference = 0.8 μmol/L) and after ML (5.3 μmol/L). However only the difference in post-ML levels was statistically significant (p < 0.001). The percentage of patients with hyperhomocysteinemia identified with the two methods was similar. Interpretation and Conclusions. The IMx method compares well with an established HPLC method for measurement of fasting tHcy plasma levels
Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding
We have identified structural attributes required for signal transduction through a seven-transmembrane-domain receptor. Platelets from a patient (AC) with a congenital bleeding disorder had normal shape change but reduced and reversible aggregation in response to 4 μM ADP, similar to normal platelets with blocked P2Y12 receptor. The response to 20 μM ADP, albeit still decreased, was more pronounced and was reduced by a P2Y12 antagonist, indicating some residual receptor function. ADP failed to lower the adenylyl cyclase activity stimulated by prostaglandin E1 in the patient's platelets, even though the number and affinity of 2-methylthioadenosine 5′-[33P]diphosphate-binding sites was normal. Analysis of the patient's P2Y12 gene revealed a G-to-A transition in one allele, changing the codon for Arg-256 in the sixth transmembrane domain to Gln, and a C-to-T transition in the other allele, changing the codon for Arg-265 in the third extracellular loop to Trp. Neither mutation interfered with receptor surface expression but both altered function, since ADP inhibited the forskolin-induced increase of cAMP markedly less in cells transfected with either mutant P2Y12 as compared with wild-type receptor. These studies delineate a region of P2Y12 required for normal function after ADP binding
Tamoxifen reduces plasma homocysteine levels in healthy women
Treatment with tamoxifen is associated with reduced incidence of myocardial infarction. As plasma homocysteine is an independent risk factor for cardiovascular disease, we studied the effects of tamoxifen on plasma homocysteine in 66 healthy women participating in the Italian prevention trial of breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg day-1 or placebo for 5 years. They were aged between 35 and 70 years, had undergone previous hysterectomy for non-malignant conditions and had no contraindications to the use of tamoxifen. Plasma levels of total homocysteine (tHcy) were measured at randomization and after 2 and 6 months. The mean ± s.d. plasma levels of tHcy were 7.59 ± 1.71 μmol l-1, 7.25 ± 1.61 and 7.09 ± 1.33 in the tamoxifen group and 8.07 ± 2.06, 7.93 ± 1.77 and 8.12 ± 2.04 in the placebo group at 0, 2 and 6 months (P = 0.008 for the between-group difference over time). The higher the baseline tHcy level, the greater was the lowering effect of tamoxifen. No statistically significant effect of age, body mass index or smoking habit on baseline tHcy levels and its variation over time was found. In conclusion, tamoxifen (20 mg day-1 for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction
Low vitamin B(6) plasma levels, a risk factor for thrombosis, in inflammatory bowel disease: role of inflammation and correlation with acute phase reactants
OBJECTIVES: Individuals with inflammatory bowel disease (IBD) are at increased risk for thrombosis and vitamin deficiencies. Low plasma levels of vitamin B6 are an independent risk factor for thrombosis and may cause hyperhomocysteinemia, another recognized risk factor for thrombosis. The aim of this study was to evaluate vitamin B6 plasma levels in IBD patients. METHODS: We studied 61 IBD patients: 32 with Crohn's disease and 29 with ulcerative colitis. For each patient, three sex- and age-matched healthy control subjects were studied. RESULTS: Median vitamin B6 levels were significantly lower in IBD patients (22.0 pmol/L, range 3.6 -231.0) than in controls (31.1 pmol/L, 3.7-363.4; p < 0.01). In all, 13.1% IBD patients and 5.5% controls had plasma vitamin B6 levels lower than the 5th percentile of distribution in normal controls (p < 0.05). Low vitamin B6 levels were significantly more frequent in patients with active disease than in patients with quiescent disease (seven of 26, 26.9%, vs one of 35, 2.9%; p < 0.001). Moreover, patients with active disease had significantly lower median vitamin B6 levels (13.4 pmol/L, range 3.6-124.0) than patients in a quiescent phase (27.0 pmol/L, 7.8-231.0; p < 0.001). Low vitamin B6 levels were significantly correlated with serum concentrations of C-reactive protein (r = -0.36, 95% CI = -0.59 to -0.09, p < 0.01) and α1-acid-glycoprotein (r = -0.37, 95% CI = -0.59 to -0.10, p < 0.01). Hyperhomocysteinemia was more frequent in patients with low vitamin B6 levels (three of eight, 37.5%) than in patients with normal levels (nine of 53, 17.0%; p = 0.18). There was no statistically significant correlation between vitamin B6 and homocysteine plasma levels (r = -0.13, 95% CI = -0.37 to +0.14, p = 0.33). CONCLUSIONS: Low vitamin B6 plasma levels, an independent risk factor for thrombosis, are frequent in patients with IBD, especially those with active disease
Atrial Fibrillation, Heart Failure Phenotypes, and Mortality Risk in the Nationwide START Registry: A Propensity Score Matching Analysis
BACKGROUND: Data on atrial fibrillation (AF) and heart failure (HF) with preserved ejection fraction (HFpEF) are scarce. We investigated the association of HFpEF with all-cause mortality in AF. METHODS: We included 10 369 patients with AF on oral anticoagulants from the nationwide ongoing START (Survey on Anticoagulated Patients Register) registry. Patients were divided into 3 groups: (1) no HF, (2) HF with reduced EF/HF with mildly reduced EF (EF ≤50%), and HFpEF (EF >50%). Patients with HF should have had a clinical diagnosis or a history of HF hospitalization. The association between HF types and all-cause mortality was investigated by Cox proportional hazards regression analysis to estimate hazard ratio (HR) and 95% CI for each factor. The Fine–Gray model and propensity score matching were used. RESULTS: Mean age was 76.4±9.4 years and 45.8% were women. Overall, 2309 (22.2%) patients had HF, of whom 47.4% had HFpEF. During 720±576 days of follow-up (20 747 patients/year), 727 deaths occurred (3.5 per 100 patient-years). After propensity score matching, both HF with mildly reduced EF/HF with reduced EF and HFpEF were associated with all-cause mortality (HR, 1.33; P=0.037 and HR, 1.49; P=0.004). HFpEF was associated with mortality in men (HR, 1.654; P=0.001) but not in women (HR, 1.243; P=0.175). In HFpEF, age≥75 years (HR, 2.247; P=0.003), chronic respiratory disease (HR, 2.109; P<0.001), anemia (HR, 1.482; P=0.035), paroxysmal AF (HR, 0.528; P=0.012), creatinine clearance<30 mL/min (HR, 1.791; P=0.018), direct oral anticoagulants (HR, 0.575; P=0.005), and renin-angiotensin inhibitors (HR, 0.670; P=0.033) were associated with all-cause mortality. CONCLUSIONS: HFpEF is frequent in patients with AF and associated with an increased mortality, especially in men. Comorbidities and treatments associated differently with mortality according to HF phenotype
Atrial Fibrillation, Heart Failure Phenotypes, and Mortality Risk in the Nationwide START Registry: A Propensity Score Matching Analysis
Background Data on atrial fibrillation (AF) and heart failure (HF) with preserved ejection fraction (HFpEF) are scarce. We investigated the association of HFpEF with all-cause mortality in AF. Methods We included 10 369 patients with AF on oral anticoagulants from the nationwide ongoing START (Survey on Anticoagulated Patients Register) registry. Patients were divided into 3 groups: (1) no HF, (2) HF with reduced EF/HF with mildly reduced EF (EF <= 50%), and HFpEF (EF >50%). Patients with HF should have had a clinical diagnosis or a history of HF hospitalization. The association between HF types and all-cause mortality was investigated by Cox proportional hazards regression analysis to estimate hazard ratio (HR) and 95% CI for each factor. The Fine-Gray model and propensity score matching were used. Results Mean age was 76.4 +/- 9.4 years and 45.8% were women. Overall, 2309 (22.2%) patients had HF, of whom 47.4% had HFpEF. During 720 +/- 576 days of follow-up (20 747 patients/year), 727 deaths occurred (3.5 per 100 patient-years). After propensity score matching, both HF with mildly reduced EF/HF with reduced EF and HFpEF were associated with all-cause mortality (HR, 1.33; P=0.037 and HR, 1.49; P=0.004). HFpEF was associated with mortality in men (HR, 1.654; P=0.001) but not in women (HR, 1.243; P=0.175). In HFpEF, age >= 75 years (HR, 2.247; P=0.003), chronic respiratory disease (HR, 2.109; P<0.001), anemia (HR, 1.482; P=0.035), paroxysmal AF (HR, 0.528; P=0.012), creatinine clearance<30 mL/min (HR, 1.791; P=0.018), direct oral anticoagulants (HR, 0.575; P=0.005), and renin-angiotensin inhibitors (HR, 0.670; P=0.033) were associated with all-cause mortality. Conclusions HFpEF is frequent in patients with AF and associated with an increased mortality, especially in men. Comorbidities and treatments associated differently with mortality according to HF phenotype
Atrial Fibrillation, Heart Failure Phenotypes, and Mortality Risk in the Nationwide START Registry: A Propensity Score Matching Analysis
BACKGROUND: Data on atrial fibrillation (AF) and heart failure (HF) with preserved ejection fraction (HFpEF) are scarce. We investigated the association of HFpEF with all-cause mortality in AF. METHODS: We included 10 369 patients with AF on oral anticoagulants from the nationwide ongoing START (Survey on Anticoagulated Patients Register) registry. Patients were divided into 3 groups: (1) no HF, (2) HF with reduced EF/HF with mildly reduced EF (EF ≤50%), and HFpEF (EF >50%). Patients with HF should have had a clinical diagnosis or a history of HF hospitalization. The association between HF types and all-cause mortality was investigated by Cox proportional hazards regression analysis to estimate hazard ratio (HR) and 95% CI for each factor. The Fine–Gray model and propensity score matching were used. RESULTS: Mean age was 76.4±9.4 years and 45.8% were women. Overall, 2309 (22.2%) patients had HF, of whom 47.4% had HFpEF. During 720±576 days of follow-up (20 747 patients/year), 727 deaths occurred (3.5 per 100 patient-years). After propensity score matching, both HF with mildly reduced EF/HF with reduced EF and HFpEF were associated with all-cause mortality (HR, 1.33; P=0.037 and HR, 1.49; P=0.004). HFpEF was associated with mortality in men (HR, 1.654; P=0.001) but not in women (HR, 1.243; P=0.175). In HFpEF, age≥75 years (HR, 2.247; P=0.003), chronic respiratory disease (HR, 2.109; P<0.001), anemia (HR, 1.482; P=0.035), paroxysmal AF (HR, 0.528; P=0.012), creatinine clearance<30 mL/min (HR, 1.791; P=0.018), direct oral anticoagulants (HR, 0.575; P=0.005), and renin-angiotensin inhibitors (HR, 0.670; P=0.033) were associated with all-cause mortality. CONCLUSIONS: HFpEF is frequent in patients with AF and associated with an increased mortality, especially in men. Comorbidities and treatments associated differently with mortality according to HF phenotype
The Italian START-Register on anticoagulation with focus on atrial fibrillation
START-Register - Survey on anTicoagulated pAtients RegisTer - is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS2 score was 2.1±1.1, CHADSVASc score was 3.1±1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) 80 years with high prevalence of renal failure
Enfermedad tromboembólica venosa en gestantes y puérperas en una institución de alta complejidad 2013 – 2019
Objective: To describe the sociodemographic and clinical characteristics and in-hospital outcomes of pregnant women and postpartum women diagnosed with venous thromboembolic disease in a high complexity institution. Materials and methods: Retrospective descriptive study, population-based, which included 52 patients with a diagnosis of Venous Thromboembolic Disease, selected among 180 medical records of pregnant and puerperal women attended in a high complexity institution in Medellin Colombia during 2013- 2019. Results: 20.9% of the pregnant women evaluated had a personal history of VTE and 17.3% were obese. Diagnosis was predominantly in the immediate postpartum period, mainly by venous doppler in 60.9% and angioCT in 11.6%. Limb pain 67.4%, asymmetric edema 44.2% and erythema 25.6% were the most frequent signs and symptoms. Complications at discharge were infrequent. Conclusions: The diagnosis of VTE was mainly made in immediate postpartum. Most of the patients diagnosed with VTE did not present complications in the immediate postpartum period. Medium and long term follow-up would be a strategy to implement.Objetivo: Describir las características sociodemográficas, clínicas y desenlaces intrahospitalarios de gestantes y puérperas con diagnóstico de Enfermedad Tromboembólica Venosa en una institución de alta complejidad. Materiales y métodos: Estudio descriptivo retrospectivo, de base poblacional, que incluyó 52 pacientes con diagnóstico de Enfermedad Tromboembólica Venosa, seleccionadas entre 180 historias clínicas de gestantes y puérperas atendidas en una institución de alta complejidad en Medellín Colombia durante 2013- 2019. Resultados: Un 20,9% de las gestantes evaluadas tenían antecedente personal de ETV y un 17,3% obesidadEl diagnóstico fue predominantemente en el posparto inmediato, mediante doppler venoso un 60,9% y angioTAC 11,6% principalmente. El dolor de extremidades 67,4%, el edema asimétrico 44,2% y el eritema 25,6% fueron los signos y síntomas más frecuentes. Las complicaciones al alta fueron poco frecuentes. Conclusiones: El diagnóstico de ETV fue realizado principalmente en posparto inmediato. La mayoría de las pacientes con diagnóstico de ETV no presentó complicaciones en dicho período. Su seguimiento en el mediano y largo plazo sería una estrategia a implementar en el ámbito institucional
