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ABSTRACT: Hyperhomocysteinemia is associated to thrombosis and atherosclerosis. Vitamin B12 is among its main causes and may be due to a pernicious anemia. This study aimed to know the prevalence of this disease in patients who have venous thromboembolism and hyperhomocysteinemia.
A total of 80 consecutive patients (55 men and 25 women; age: mean [standard deviation] 63 [15] years) with pulmonary embolism and/or venous thrombosis and elevated values of homocysteine (> 12 micromol/l) were studied.
Pernicious anemia was diagnosed (positive Schilling test, presence of anti-intrinsic factor antibodies and/or anti-parietal cells and fundal atrophic gastritis) in 5 patients (6.25% with range of age: 42-73 years. Only one of them had macrocytic anemia and there were no alterations in any of them in the thrombophilia study. The patients were treated with vitamin B12, administering it orally (1 mg/day) in 4 of them. The homocysteine and vitamin B12 values were normalized in every case at 6 months.
Although the prevalence of pernicious anemia is not elevated in patients with venous thromboembolism and hyperhomocysteinemia, its existence must be ruled out to avoid other thrombotic and neurological complications.
Revista Clínica Española 10/2005; 205(10):489-92. · 2.01 Impact Factor
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ABSTRACT: Hyperhomocysteinemia has been recently described in patients with inflammatory bowel disease (IBD), that could be related to the increased risk for thrombosis that exists in this disease. The aim of this study was the assessment of hyperhomocysteinemia in patients with IBD and its relation among vitamin B12 and folate levels, and methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C mutations.
Fifty two consecutive patients with IBD were studied (29 women and 23 men); age: mean (standard deviation 41.7 [11.9] years) and 186 controls with no difference in age and gender. Hyperhomocysteinemia was considered as homocysteine levels higher than mean plus two standard deviations of the control group (> or = 13 micromol/l).
patients had an elevated prevalence of hyperhomocysteinemia (17.3 vs. 3.7%; p = 0.002) and lower folate (7.6 [4.1] vs. 8.9 [3.7] ng/ml; p = 0.01) and B12 vitamin levels (499 [287] vs. 603 [231] pg/ml; p = 0.003). Homocysteinemia was higher (14.3 [5.8] vs. 9.1 [3.9] micromol/l; p = 0.006) in 6 patients (11.5%) that had suffered thromboembolism. Frequency of MTHFR 677C-->T (13.5 vs. 11.3%; p = 0.66) and 1298A-->C (7.8 vs. 7.0%; p = 0.76) mutations was not increased in patients. Odds ratio (OR) for IBD in hyperhomocysteinemic patient was 5.51, 95% confidence interval (CI), 1.81-16.76; p = 0.002). Hyperhomocysteinemia was negatively associated with feminine gender (OR 0.08, 95% CI 0.01-0.49; p = 0.006) and folate levels (OR 0.04, 95%CI: 0.007-0.20; p < 0.001).
hyperhomocysteinemia is associated with IBD and low folate levels, and could be involved in development of thromboembolism. MTHFR 677C-->T and 1298A-->C mutations are not related with the disease.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 08/2005; 97(7):497-504. · 1.55 Impact Factor
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Revista Clínica Española 12/2004; 204(11):607-8. · 2.01 Impact Factor
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Anales de medicina interna (Madrid, Spain: 1984) 09/2003; 20(8):443-4.
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Clinical Chemistry 12/2001; 47(11):2037-40. · 7.91 Impact Factor
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ABSTRACT: B-mode ultrasonography is a simple and valid method to evaluate subclinical atherosclerosis of the major superficial arteries. The aim of this study was toknow by this technique the prevalence of carotid atherosclerosisin patients with coronary disease and related factors.
In 232patients (205 men and 27 women; age: mean [standard deviation]59 [8] years) with coronary disease, intima-media thickness (IMT),presence and number of atheroma plaques in carotid arteries wereevaluated by B-mode ultrasonography. Controls were 50 healthy subjects whose age was not different from patients. Carotid atherosclerosis was considered when IMT was higher than mean plus two standarddeviations of control values, and/or existence of atheroma plaques.
Carotid IMT wasincreased in patients compared to controls 0.82 [0.22] vs 0.62[0.12] mm; p < 0.001) and there were more patients with plaques(67 vs 20%; p < 0.001). Carotid atherosclerosis was found in170 patients and 11 controls (73 vs 22%; p < 0.001). By multivariate analysis, carotid atherosclerosis was associated with age (oddsratio: 1.05; 95% confidence interval [CI], 1.01-1.09) and smoking(odds ratio, 2.11; 95% CI: 1.04-4.26). The presence of more thanone plaque was associated with levels of low-density-lipoprotein(LDL)-cholesterol (odds ratio, 1.01; 95% CI, 1.00-1.02).
In the patients with coronary disease, prevalence of subclinical carotid atherosclerosisis very high (73%), and it is associated with age and smoking. The advanced stage of atherosclerosis, evaluated by the existence of more than one plaque, is correlated with LDL-cholesterol levels.
Medicina Clínica 04/2001; 116(12):441-5. · 1.38 Impact Factor
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ABSTRACT: Some studies have found that postmenopausal women have increased plasma homocysteine levels while others do not. The aim of this study was to know if homocysteine levels are increased in Spanish postmenopausal women.
In 100 postmenopausal women (age: mean [SD] 56 [6] years) homocysteine, creatinine, folic acid, vitamin B12 and lipoproteins were determined. Controls were 50 premenopausal women (age: 29 [6] years), 50 men with similar age to postmenopausal women, and 50 men with similar age to premenopausal women. All the subjects of the study were healthy.
Homocysteine concentrations were higher in postmenopausal compared with premenopausal women (8.6 [2.1]; 95% confidence interval [CI], 8.2-9.1 vs 7.7 [1.6]; 95% CI, 7.2-8.1 micromol/l; p < 0.05), but were not different between both men groups. Hyperhomocysteinemia was found in 9 postmenopausal but in any premenopausal women (9% vs 0%; p = 0.03). Low density lipoprotein cholesterol values were higher (155 [32]; 95% CI, 148-161 vs 111 [32]; 95% CI, 101-120 mg/dl; p < 0.05), and high density lipoprotein cholesterol lower (54 [12]; 95% CI, 52-57 vs 64 [18]; 95% CI, 59-69 mg/dl; p < 0.05) in postmenopausal than premenopausal women. In postmenopausal women homocysteine levels were negatively associated with folic acid and positively associated with creatinine levels, but there was not association with age, vitamin B12 serum levels and lipoproteins.
In postmenopausal women increased homocysteine concentrations, together with hypercholesterolemia, could contribute to the raise of their cardiovascular risk.
Medicina Clínica 03/2001; 116(6):206-8. · 1.38 Impact Factor
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Anales de medicina interna (Madrid, Spain: 1984) 05/2000; 17(4):220-1.
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ABSTRACT: There have been discrepancies in reports of total cholesterol and low density lipoprotein (LDL)-cholesterol levels in patients with acute porphyria. Some studies have found that acute porphyria patients have increased levels while others do not. The aim of this study has been to evaluate the lipid profile in a series of patients with acute porphyria, in order to help clarify these differences. Serum lipoprotein levels were studied in 30 patients (25 women and five men; age:38+/-10 years) with asymptomatic acute porphyria. Controls were 30 healthy volunteers matched for age and gender. For 13 patients and 15 controls, lipoprotein lipase and hepatic lipase activities were determined. Patients exhibited increased levels of total-cholesterol, LDL-cholesterol, high density lipoprotein (HDL)-cholesterol and apolipoprotein (apo)-A1 compared with controls (P4 mmol/l in 15 patients (50%). Levels of total triglycerides, very low density lipoprotein (VLDL)-triglycerides, VLDL-cholesterol, apo-B and lipoprotein(a) were similar in patients and controls. The hepatic lipase activity tended to be lower in patients than controls (33.8+/-17.7 vs. 50.4+/-23.0 pkat/ml; P=0.05). In conclusion, in patients with asymptomatic acute porphyria an increase of total and LDL-cholesterol was found. The cardiovascular risk conferred by this factor may be attenuated by increased HDL-cholesterol and apo-A1.
Clinica Chimica Acta 05/2000; 294(1-2):37-43. · 2.54 Impact Factor
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ABSTRACT: Hyperhomocysteinemia, an independent risk cardiovascular factor, has been reported in renal transplanted patients (RTP). The aim of the present study was to evaluate homocysteine levels in RTP treated with cyclosporine or tacrolimus, and the changes observed in the two groups of patients after treatment with folic acid. Forty-two RTP with stable function (21 treated with cyclosporine and 21 with tacrolimus, matched by gender and age) were studied. Forty healthy control subjects were matched by age and gender with the patients. In RTP, homocysteine was increased compared with the controls (16.4 +/-5.2 vs 8.0 +/- 1.8 micromol/L; p < 0.001), but there was no difference in vitamin B12 and folic acid levels. Thirty-three patients and one control showed hyperhomocysteinemia (78.5 vs 2.5%; p < 0.001). Homocysteine correlated negatively with creatinine clearance in the patients (p = 0.04), but no correlation was found with vitamin B12, folic acid and lipoproteins. By univariate analysis, patients treated with cyclosporine had higher homocysteine than those treated with tacrolimus (p = 0.03), but multivariate analysis did not confirm these results. In 21 patients with hyperhomocysteinemia and folate levels similar to those of the controls, folic acid (5 mg/d for 3 months) was administered. Homocysteine decreased significantly (19.1 +/- 4.8 vs 13.2 +/- 3.4 micromol/L; p < 0.001), with a median reduction of 31% and with no differences observed in patients treated with either cyclosporine or tacrolimus. We concluded that hyperhomocysteinemia is very frequent in RTP, but homocysteine levels are not different in patients treated with cyclosporine or tacrolimus. Folic acid therapy produces a significant decrease in homocysteine concentrations, in the absence of clear folate deficiency, without differences in relation to immunosuppressant therapy.
Clinical Transplantation 04/2000; 14(2):110-4. · 1.67 Impact Factor
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ABSTRACT: Previous studies have found that hyperhomocysteinemia is an independent risk factor for coronary disease. Homocysteine levels, and factors involved in their increase, are unknown in Spanish patients with coronary disease.
In 202 Spanish patients with coronary disease (174 men and 28 women) and age < 70 years old, homocysteine, creatinine, fibrinogen, lipoproteins, folic acid and vitamin B12 levels were determined. Controls were 40 healthy subjects whose age was not different from patients.
Plasma homocysteine levels were increased in patients compared to controls (mean [SD] 11.7 [4.2], 95% confidence interval [CI]: 11.1-12.2, vs 8.4 [2.4], 95% CI: 7.7-9.2 mumol/l; p < 0.001). Hyperhomocysteinemia was found in 52 patients and in one control (26% vs 2.5%, odds ratio: 13.5, 95% CI: 1.8-100.8; p = 0.001). Homocysteine levels were positively associated in patients with creatinine level and negatively associated with folic acid level (p = 0.02 for both), but association with age, gender, fibrinogen, lipoproteins and vitamin B12 was not found. By multivariate analysis, folic acid was the only independent variable related with homocysteine levels (odds ratio: 0.32%, 95% CI: 0.122-0.882). In a subgroup of 30 patients with a low profile of cardiovascular risk (total-cholesterol < 225 mg/dl, nonsmokers and without diabetes and hypertension) an increase of homocysteine levels was also found, and 33% of them had hyperhomocysteinemia.
Hyperhomocysteinemia was present in 26% of the patients with coronary disease. A similar percentage was found in the patients with a low profile of cardiovascular risk. Homocysteine levels were negatively associated with folic acid levels.
Medicina Clínica 10/1999; 113(11):407-10. · 1.38 Impact Factor
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ABSTRACT: Hyperlipemia is frequent in liver transplanted patients and has been related with the existence of cholestasis, renal insufficiency, obesity, diabetes, and especially with immunosuppressant treatment. Although there are no studies that show a relationship between post-liver transplant hyperlipemia and the development of cardiovascular disease, there are data that indicate that liver transplanted patients should control their cholesterol levels to reduce the incidence of this disease. When post-transplant hyperlipemia is present, hygienic-dietary measures should be established and treatment should be carried out with the minimum dose of cyclosporine needed to maintain the graft stable. Corticoids should be discontinued as soon as possible. Treatment with some statins (Lovastatin and Pravastatin) has shown to be safe and efficacy in the liver transplanted patients with hypercholesterolemia.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 10/1999; 91(9):645-9. · 1.55 Impact Factor
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ABSTRACT: To know the lipid profile in patients with porphyria cutanea tarda (PCT).
Serum lipoproteins have been studied in 64 males with PCT: 42 with chronic hepatitis C and 22 seronegatives for hepatitis B and C virus. Thirteen patients without porphyria, but with chronic hepatitis C, and 13 healthy subjects were also studied.
Patients with chronic hepatitis C, with or without PCT, had a decrease of total and VLDL cholesterol (TC and VLDLc) and apolipoprotein (apo) B in comparison with healthy controls and seronegative for hepatitis C virus patients with PCT.
Lipid abnormalities found in PCT are not related with this disease, but with the presence of chronic hepatitis C often associated to PCT.
Medicina Clínica 06/1999; 112(17):656-7. · 1.38 Impact Factor
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Medicina Clínica 04/1999; 112(11):438. · 1.38 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the effects of interferon-alpha therapy on the lipid profile of patients with chronic hepatitis C.
In 36 consecutive patients with chronic hepatitis C, fasting lipoproteins were evaluated prospectively at baseline, 1, 3 and 6 months during interferon-alpha therapy and 3 months after the end of treatment.
During interferon-alpha therapy, there was a progressive increase in total and very low density lipoprotein (VLDL)-triglycerides, VLDL-cholesterol and a sustained raise in apolipoprotein (apo) B. In parallel, there was a reduction in high density lipoprotein (HDL)-cholesterol and apo A1 levels. In contrast, total and low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels remained essentially unchanged during interferon-alpha therapy. Three patients developed chylomicronemia, two of them with severe hypertriglyceridemia, although none of them presented with pancreatitis. Chylomicronemia and severe hypertriglyceridemia were more common in patients with basal triglycerides above 200 mg/dl. Nineteen patients responded to interferon-alpha therapy, but their lipid profile did nor differ from that of nonresponders. Three months after the end of interferon-alpha therapy lipid changes subsided, although VLDL and HDL-cholesterol and apo B did not reach basal levels.
In patients with chronic hepatitis C, interferon-alpha therapy is associated with an increase of total and VLDL-triglycerides, VLDL-cholesterol and apo B, and a decline of HDL-cholesterol and apo A1. The development of chylomicronemia and severe hypertriglyceridemia in some cases makes mandatory a close monitoring of triglycerides during interferon-alpha therapy, particularly among patients with increased triglycerides at baseline.
The American Journal of Gastroenterology 11/1998; 93(10):1901-4. · 7.28 Impact Factor
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ABSTRACT: In order to determine lipid abnormalities in serum in HIV-infected patients and their relation with humoral and cellular immunological changes. Ninety HIV-infected patients without acute inflammatory or malignant disease have been studied. Thirty healthy HIV-negative subjects constituted the control group. As compared with controls, patients with CD4 + lymphocytes > 400 x 10(6)/l had higher triglycerides and lower high density lipoprotein (HDL)-cholesterol and apolipoprotein (apo)-A1. Lipoprotein comparison by groups of patients according to CD4 + cell counts showed a decrease of HDL-cholesterol in patients with CD4 + cells < or = 200 x 10(6)/l. When CD4 + lymphocyte counts were < 50 x 10(6)/l, total and very low density lipoprotein (VLDL)-triglycerides and VLDL-cholesterol were increased and HDL and low density lipoprotein (LDL)-cholesterol and apo-A1 were decreased. Interferon (IFN)-alpha, beta2-microglobulin and tumor necrosis factor (TNF)-alpha were correlated positively with total and VLDL-triglycerides and negatively with HDL-cholesterol. In conclusion, lipoprotein changes in patients with HIV-infection are related with humoral and cellular immune markers. A decrease of HDL-cholesterol and apo-A1 and an increase of triglyceride levels could be considered as markers of disease progression.
Clinica Chimica Acta 06/1998; 274(1):63-70. · 2.54 Impact Factor
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C Fernández-Miranda,
A de la Calle,
J M Morales,
C Guijarro,
J L Aranda,
R Gómez-Sanz,
T Gómez-Izquierdo,
S Larumbe,
E Moreno,
J L Rodicio,
A del Palacio
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ABSTRACT: Hyperlipidemia is a common feature after organ transplantation. Most studies have evaluated the lipid profile in recipients of a particular graft, usually renal. In the present work, we studied the lipid profiles of 30 long-term stable liver transplant patients (LTP) and compared their pattern with 40 long-term stable renal transplant patients (RTP) matched for gender, age, and time from transplantation. There were no significant differences between both groups in body mass index, serum glucose, serum creatinine, or urinary protein excretion. In contrast, RTP had higher pre-transplant total cholesterol and triglycerides, received higher doses of steroids (both average and cumulative) and had higher cycosplorine blood levels. After a mean time of 60 months after transplantation, RTP exhibited higher levels of total serum cholesterol (226 +/- 26 vs. 180 +/- 39 mg/dl; p = 0.000 002) and low-density lipoprotein (LDL) cholesterol (152 +/- 22 vs. 112 +/- 37 mg/dl; p = 0.00001). In contrast, there were no differences between RTP and LTP in high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, total triglycerides, VLDL triglycerides, or lipoprotein (a) [Lp(a)]. By univariate analysis in the whole group, renal graft, prednisone daily dose, cyclosporine blood levels, pre-transplant cholesterol, and triglycerides were associated with increased post-transplant cholesterol levels. By multivariate analysis, prednisone daily dose was the only independent variable predicting increased post-transplant serum cholesterol levels. The present data show that hypercholesterolemia is more frequent among RTP than among LTP. In addition, our data suggest that corticosteroid therapy, rather than the transplanted organ, may be the major contributor to this difference.
Clinical Transplantation 04/1998; 12(2):136-41. · 1.67 Impact Factor
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ABSTRACT: Dyslipidemia is common after liver transplantation, but the underlying mechanisms are largely unknown. We studied the lipid profile of 27 liver transplant recipients randomized to received either cyclosporin (CyA, n = 14) or tacrolimus (n = 13) and compared them with 20 healthy, matched controls. Before transplantation, patients presented low total and low-density lipoprotein (LDL) cholesterol (as compared to controls) that increased shortly, i.e., 3 months, after transplantation. Eighteen months post-transplantation, total and LDL cholesterol levels decreased to pre-transplant values but tended to remain higher in CyA-treated patients. However, at that time, prednisone treatment was more prevalent among CyA-treated than tacrolimus-treated patients and fully accounted for the difference in cholesterol levels. Indeed, regardless of therapy, patients not receiving prednisone exhibited lower cholesterol levels than prednisone-treated patients and controls. We conclude that prednisone therapy, rather than CyA or tacrolimus immunosuppression, seems to be the major determinant of increased cholesterol levels.
Transplant International 02/1998; 11(2):137-42. · 2.92 Impact Factor
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ABSTRACT: The aim of this study has been to confirm that liver is the main site of apolipoprotein (apo) E and apo(a) synthesis, based in the changes of their phenotypes after transplantation. Apo E phenotypes were studied in 34 patients and apo(a) phenotypes in 27 of them before and after liver transplant. Thirteen patients changed the apo E phenotype after transplantation. Eight patients with E3/3 phenotype changed to the others with 2 or 4 alleles. Three patients with E4/3 phenotype changed to E3/3, one changed from E3/2 to E3/3 and another one changed from E4/2 to E3/2 phenotype after transplantation. Twenty one of the 27 patients changed the apo(a) phenotype. Thirteen of them also changed lipoprotein (Lp)(a) serum concentration at least twofold, showing in 11 an increase and in 2 a decrease, in relation with the change to phenotype associated with high and low Lp(a) concentration, respectively. Changes in apo E and apo(a) phenotypes in liver transplant recipients studied show that most of these apolipoproteins are synthesized by the liver.
Clinical Transplantation 09/1997; 11(4):325-7. · 1.67 Impact Factor
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ABSTRACT: To evaluate whether males with testicular cancer treated with chemotherapy including cisplatin (Qt-C) develop an increase in serum cholesterol and triglyceride levels and in the body mass index (BMI), which might pose a cardiovascular risk.
Fifty-six male patients with the previous diagnosis of testicular carcinoma, and apparently cured now, were studied. Thirty-six were Qt-C treated. The median age was 28 years and the median follow-up 81 months. The other 20 patients, with testicular cancer stage I and who did not require Qt-C, did not differ in mean age nor in the median of follow-up. Twenty healthy males were also studied, and their cholesterol and triglyceride levels and BMI were compared with those in patients treated with Qt-C at the end of follow-up; both group were of similar age. In all patients (prior to diagnosis and yearly up to the end of the study) and in healthy subjects total serum cholesterol and triglyceride levels were measured, as well as BMI (weight/height2).
Levels of cholesterol, triglycerides and BMI were not different at diagnosis of testicular cancer, both in patients treated with Qt-C and those not receiving such therapy. When comparing yearly cholesterol and triglyceride levels in both groups of patients during the first 6 years of evolution, no significant differences were observed. Again, no differences were observed between patients treated and not treated with Qt-C at the end of the follow-up period regarding cholesterol (211 +/- 41 vs 219 +/- 44 mg/dl; p = 0.51), triglyceride (128 +/- 57 vs 129 +/- 51 mg/dl; p = 0.94) and BMI (25.7 +/- 3.3 vs 25.5 +/- 3.4 kg/m2; p = 0.86) values. No significant differences were observed in the three parameters between parameters in patients treated with Qt-C at the end of follow-up and in healthy males.
In males with testicular cancer treated with Qt-C, no long term increase in cholesterol, triglyceride, and BMI values was detected, which might predispose to the development of cardiovascular diseases.
Revista Clínica Española 08/1997; 197(7):490-3. · 2.01 Impact Factor
