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      Plasma Homocysteine Levels and Late Outcome in Patients with Unstable Angina

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      , , , ,
      Cardiology
      S. Karger AG
      Homocysteine, Unstable angina

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          Abstract

          Aim of the Study: Previous studies have suggested that total plasma homocysteine (HCY) is an important cardiovascular risk factor because of its interaction with vascular smooth muscle cells, endothelium function, plasma lipoprotein, coagulation factors and platelets. The aim of this study was to evaluate a possible relationship between HCY levels and the severity of coronary artery disease (CAD) and its prognostic value in patients with unstable angina (UA). Methods and Results: Ninety-four patients with UA were recruited and underwent coronary angiography and in some cases myocardial revascularization. The primary end point was the severity of CAD. The clinical end points were the recurrence of UA and the compositive end point of the occurrence of cardiac death and re-hospitalization due to acute coronary syndrome. HCY levels were shown to be poorly correlated with the severity of CAD. After 48 months’ of follow-up, a graded relationship between HCY levels and recurrence of UA and compositive end point was found (p < 0.001). Conclusions: In the light of events occurring during the follow-up period, it was concluded that total plasma HCY is a strong predictor of recurrence of UA.

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          Most cited references9

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          Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.

          Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. Case-control study. Nineteen centers in 9 European countries. A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.
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            A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians.

            To assess prospectively the risk of coronary heart disease associated with elevated plasma levels of homocyst(e)ine. Nested case-control study using prospectively collected blood samples. Participants in the Physicians' Health Study. A total of 14,916 male physicians, aged 40 to 84 years, with no prior myocardial infarction (MI) or stroke provided plasma samples at baseline and were followed up for 5 years. Samples from 271 men who subsequently developed MI were analyzed for homocyst(e)ine levels together with paired controls, matched by age and smoking. Acute MI or death due to coronary disease. Levels of homocyst(e)ine were higher in cases than in controls (11.1 +/- 4.0 [SD] vs 10.5 +/- 2.8 nmol/mL; P = .03). The difference was attributable to an excess of high values among men who later had MIs. The relative risk for the highest 5% vs the bottom 90% of homocyst(e)ine levels was 3.1 (95% confidence interval, 1.4 to 6.9; P = .005). After additional adjustment for diabetes, hypertension, aspirin assignment, Quetelet's Index, and total/high-density lipoprotein cholesterol, this relative risk was 3.4 (95% confidence interval, 1.3 to 8.8) (P = .01). Thirteen controls and 31 cases (11%) had values above the 95th percentile of the controls. Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors. Because high levels can often be easily treated with vitamin supplements, homocyst(e)ine may be an independent, modifiable risk factor.
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              Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study.

              To estimate the relations between established cardiovascular risk factors and total homocysteine (tHcy) in plasma. Health examination survey by the Norwegian Health Screening Service in 1992 and 1993. General community, Hordaland County of Western Norway. A total of 7591 men and 8585 women, 40 to 67 years of age, with no history of hypertension, diabetes, coronary heart disease, or cerebrovascular disease were included. Plasma tHcy level. The level of plasma tHcy was higher in men than in women and increased with age. In subjects 40 to 42 years old, geometric means were 10.8 mumol/L for 5918 men and 9.1 mumol/L for 6348 women. At age 65 to 67 years, the corresponding tHcy values were 12.3 mumol/L (1386 men) and 11.0 mumol/L (1932 women). Plasma tHcy level increased markedly with the daily number of cigarettes smoked in all age groups. Its relation to smoking was particularly strong in women. The combined effect of age, sex, and smoking was striking. Heavy-smoking men aged 65 to 67 years had a mean tHcy level 4.8 mumol/L higher than never-smoking women aged 40 to 42 years. Plasma tHcy level also was positively related to total cholesterol level, blood pressure, and heart rate and inversely related to physical activity. The relations were not substantially changed by multivariate adjustment, including intake of vitamin supplements, fruits, and vegetables. Elevated plasma tHcy level was associated with major components of the cardiovascular risk profile, ie, male sex, old age, smoking, high blood pressure, elevated cholesterol level, and lack of exercise. These findings should influence future studies on the etiology and pathogenesis of cardiovascular disease.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2007
                May 2007
                01 February 2007
                : 107
                : 4
                : 354-359
                Affiliations
                University of Brescia, Chair of Cardiology, Brescia, Italy
                Article
                99050 Cardiology 2007;107:354–359
                10.1159/000099050
                17283425
                3ce25b7c-822c-4129-8f7d-ff72d5f66061
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 17 October 2005
                : 10 September 2006
                Page count
                Figures: 6, Tables: 3, References: 22, Pages: 6
                Categories
                Original Research

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Homocysteine,Unstable angina

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