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      Reduced Concentrations of Soluble Adhesion Molecules after Antioxidant Supplementation in Postmenopausal Women with High Cardiovascular Risk Profiles – A Randomized Double-Blind Study

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          Abstract

          Background: One of the suggested mechanisms of increased cardiovascular risk in postmenopause is a loss of the antioxidant effects of estrogens. It has been shown that classical cardiovascular risk factors increase oxidative stress on the arterial wall, and that endothelial cells react to this insult by increased expression of cellular adhesion molecules (CAM), which in turn are markers of arterial wall inflammation. Methods: A randomized, placebo-controlled, double-blind study was performed in 60 postmenopausal women with high cardiovascular risk profiles, but free from clinical atherosclerotic disease. Patients were randomized to either antioxidant supplementation (using a combination of natural antioxidants; n = 30) or placebo (n = 30), and followed for 12 weeks. The concentrations of the adhesion molecules sVCAM-1 and sICAM-1 were measured by ELISA at baseline and at the end of the study, as well as total cholesterol, LDL, HDL, triglycerides and blood pressure. Results: 27 women in the antioxidant supplementation group and 29 on placebo completed the study. At baseline, there were no significant differences in measured parameters between the groups: sICAM-1 concentrations were 341.8 ± 116.9 vs. 349.9 ± 104.6 ng/ml (active treatment vs. placebo; p = n.s.) and sVCAM-1 concentrations were 780.5 ± 325.8 vs. 761.0 ± 333.7 ng/ml (p = n.s.). In contrast, at the end of the study, sICAM-1 concentrations were 301.6 ± 56.0 vs. 356.0 ± 134.8 ng/ml (active treatment vs. placebo; p = 0.053) and sVCAM-1 concentrations were 656.0 ± 326.5 vs. 818.5 ± 381.0 ng/ml (p = 0.04). There were no significant differences between or changes within the groups in measured cholesterol and blood pressure. Conclusion: Antioxidant supplementation reduces serum concentrations of endothelium-derived adhesion molecules sICAM-1and sVCAM-1 in postmenopausal women with high cardiovascular risk profiles.

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          Most cited references 8

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          Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.

           S Yusuf,  J Pogue,  P Bosch (2000)
          Observational and experimental studies suggest that the amount of vitamin E ingested in food and in supplements is associated with a lower risk of coronary heart disease and atherosclerosis. We enrolled a total of 2545 women and 6996 men 55 years of age or older who were at high risk for cardiovascular events because they had cardiovascular disease or diabetes in addition to one other risk factor. These patients were randomly assigned according to a two-by-two factorial design to receive either 400 IU of vitamin E daily from natural sources or matching placebo and either an angiotensin-converting-enzyme inhibitor (ramipril) or matching placebo for a mean of 4.5 years (the results of the comparison of ramipril and placebo are reported in a companion article). The primary outcome was a composite of myocardial infarction, stroke, and death from cardiovascular causes. The secondary outcomes included unstable angina, congestive heart failure, revascularization or amputation, death from any cause, complications of diabetes, and cancer. A total of 772 of the 4761 patients assigned to vitamin E (16.2 percent) and 739 of the 4780 assigned to placebo (15.5 percent) had a primary outcome event (relative risk, 1.05; 95 percent confidence interval, 0.95 to 1.16; P=0.33). There were no significant differences in the numbers of deaths from cardiovascular causes (342 of those assigned to vitamin E vs. 328 of those assigned to placebo; relative risk, 1.05; 95 percent confidence interval, 0.90 to 1.22), myocardial infarction (532 vs. 524; relative risk, 1.02; 95 percent confidence interval, 0.90 to 1.15), or stroke (209 vs. 180; relative risk, 1.17; 95 percent confidence interval, 0.95 to 1.42). There were also no significant differences in the incidence of secondary cardiovascular outcomes or in death from any cause. There were no significant adverse effects of vitamin E. In patients at high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes.
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            Risks of leukaemia and solid tumours in individuals with Down's syndrome.

            Individuals with Down's syndrome have a greater risk of leukaemia than the general population, but reliable estimates of the age-specific risk are lacking and little is known about the risk of solid tumours. We identified 2814 individuals with Down's syndrome from the Danish Cytogenetic Register, and linked the data to the Danish Cancer Registry. The number of person-years at risk was 48453. Standardised incidence ratio (SIR) and 95% CI were calculated of the basis of cancer rates specific for age and sex in the general population. 60 cases of cancer were found, with 49.8 expected (SIR 1.20 [95% CI 0.92-1.55]). Leukaemia constituted 60% of cases of malignant disease overall and 97% of cases in children. The SIR for leukaemia varied with age, being 56 (38-81) at age 0-4 years and 10 (4-20) at 5-29 years. No cases of leukaemia were seen after the age of 29 years. The SIR for acute myeloid leukaemia was 3.8 (1.7-8.4) times higher than that for acute lymphoblastic leukaemia in children aged 0-4 years. The cumulative risk for leukaemia by the age of 5 years was 2.1% and that by 30 years was 2.7%. Only 24 solid tumours were seen, with 47.8 expected (0.50 [0.32-0.75]). No cases of breast cancer were found, with 7.3 expected (p=0.0007). Higher than expected numbers of testicular cancers, ovarian cancers, and retinoblastomas were seen but were not significant. INTREPRETATION: The occurrence of cancer in Down's syndrome is unique with a high risk of leukaemia in children and a decreased risk of solid tumours in all age-groups. The distinctive pattern of malignant diseases may provide clues in the search for leukaemogenic genes and tumour-suppressor genes on chromosome 21.
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              Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women.

               L Kushi,  Y. Wu,  R Prineas (1996)
              The role of dietary antioxidant vitamins in preventing coronary heart disease has aroused considerable interest because of the knowledge that oxidative modification of low-density lipoprotein may promote atherosclerosis. We studied 34,486 postmenopausal women with no cardiovascular disease who in early 1986 completed a questionnaire that assessed, among other factors, their intake of vitamins A, E, and C from food sources and supplements. During approximately seven years of follow-up (ending December 31, 1992), 242 of the women died of coronary heart disease. In analyses adjusted for age and dietary energy intake, vitamin E consumption appeared to be inversely associated with the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21,809 women who did not consume vitamin supplements (relative risks from lowest to highest quintile of vitamin E intake, 1.0, 0.68, 0.71, 0.42, and 0.42; P for trend 0.008). After adjustment for possible confounding variables, this inverse association remained (relative risks from lowest to highest quintile, 1.0, 0.70, 0.76, 0.32, and 0.38; P for trend, 0.004). There was little evidence that the intake of vitamin E from supplements was associated with a decreased risk of death from coronary heart disease, but the effects of high-dose supplementation and the duration of supplement use could not be definitely addressed. Intake of vitamins A and C did not appear to be associated with the risk of death form coronary heart disease. These results suggest that in postmenopausal women the intake of vitamin E from food is inversely associated with the risk of death from coronary heart disease and that such women can lower their risk without using vitamin supplements. By contrast, the intake of vitamins A and C was not associated with lower risks of dying from coronary 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
                2000
                April 2001
                26 April 2001
                : 94
                : 4
                : 227-232
                Affiliations
                aPreventive Cardiology Clinic, Department of Internal Medicine 2, Medical University of Sofia, bDepartment of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, c2nd Hospital of Obstetrics and Gynecology, Sofia, Bulgaria, and dHeart Center, Division of Cardiology B, State University Hospital (Rigshospitalet), Copenhagen, Denmark
                Article
                47322 Cardiology 2000;94:227–232
                10.1159/000047322
                11326143
                © 2001 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.

                Page count
                Figures: 1, Tables: 2, References: 41, Pages: 6
                Categories
                General Cardiology

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