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      Low Serum Glutathione Peroxidase Activity Is Associated with Increased Cardiovascular Mortality in Individuals with Low HDLc’s

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          Abstract

          Background

          Since oxidized LDL is thought to initiate atherosclerosis and the serum glutathione peroxidase (GPx3) reduces oxidized lipids, we investigated whether high GPx3 activity reduces cardiovascular disease (CVD) mortality.

          Methods

          We determined GPx3 in stored samples from the Minnesota Heart Survey of 130 participants who after 5 to 12 years of follow-up had died of CVD and 240 controls. Participants were 26 to 85 years old and predominantly white. In a nested case-control, study we performed logistic regressions to calculate odds ratios (OR) adjusted for age, sex, baseline year, body mass index, smoking, alcohol intake, physical activity, total and HDL cholesterols, systolic blood pressure, serum glucose and gamma glutamyltransferase (GTT) activity. The referent was the quartile with the highest GPx3 activity (quartile 4).

          Results

          OR’s for CVD mortality for increasing quartiles of GPx3 were 2.37, 2.14, 1.83 and 1.00 (P for trend 0.02). This inverse correlation was confined to those with HDLc’s below the median (P for interaction, 0.006). The OR’s for increasing quartiles of GPx3 in this group were 6.08, 5.00, 3.64 and 1.00 (P for trend, 0.002).

          Conclusions

          Individuals with both low HDLc and GPx3 activity are at markedly increased risk for death from CVD.

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          Most cited references22

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          Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity.

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            Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.

            There is accumulating data that acute coronary syndromes relate to recent onset activation of inflammation affecting atherosclerotic plaques. Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a role in these circumstances. Ox-LDL levels were measured in 135 patients with acute myocardial infarction (AMI; n=45), unstable angina pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were significantly higher than in patients with UAP (P<0.0005) or SAP (P<0.0001) or in controls (P<0.0001) (AMI, 1.95+/-1.42 ng/5 microgram LDL protein; UAP, 1.19+/-0.74 ng/5 microgram LDL protein; SAP, 0.89+/-0.48 ng/5 microgram LDL protein; control, 0.58+/-0.23 ng/5 microgram LDL protein). Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In the atherectomy specimens, the surface area containing ox-LDL-positive macrophages was significantly higher in patients with UAP than in those with SAP (P<0.0001). This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL-positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.
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              A simultaneous evaluation of 10 commonly used physical activity questionnaires.

              Ten commonly used physical activity questionnaires were evaluated for reliability and validity in 78 men and women aged 20-59, with varying physical activity habits. One month reliability was found to be high for all questionnaires except those pertaining only to the last week or month. Longer term test-retest reliability tended to be lower. Validity was studied in relation to treadmill exercise performance, vital capacity, body fatness, the average of 14 4-wk physical activity histories and the average of 14 2-d accelerometer readings. No questionnaire measure was correlated with the accelerometer reading, and correlations with vital capacity were generally low. Only the Minnesota Leisure Time Physical Activity Questionnaire household chores measure was correlated with habitual performance of household chores. Most questionnaires, even very simple ones, were related to performance of heavy intensity physical activity and treadmill performance; these same questionnaires tended to be related to percent body fat. Fewer questionnaires related to performance of light or moderate activity. Occupational activity was unrelated to any of the validation measures. It is concluded that there are multiple, nonoverlapping dimensions of physical activity, reflected in multiple nonoverlapping validation realms. More important than the length or attention to detail of a questionnaire seems to be the logic of its questions. Important areas of physical activity that should be addressed in future questionnaires include sleep, light, moderate and heavy intensity leisure activities, household chores, and occupational activity. Recent versus habitual activity should also be considered.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                15 June 2012
                : 7
                : 6
                : e38901
                Affiliations
                [1 ]Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America
                [2 ]Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
                [3 ]Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America
                [4 ]Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America
                [5 ]Division of Environmental Health Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America
                [6 ]Division of Preventive Medicine, School of Medicine, Kyungpook National University, Jung-gu, Daegu, South Korea
                [7 ]Department of Nutrition, University of Oslo, Oslo, Norway
                University of Freiburg, Germany
                Author notes

                Conceived and designed the experiments: DRJ JLH. Performed the experiments: RRE. Analyzed the data: BB DHL LS RVL DRJ. Wrote the paper: DRJ.

                Article
                PONE-D-12-06547
                10.1371/journal.pone.0038901
                3376150
                22719980
                fedb2399-20e2-4744-8e9b-36ae446997f4
                Buijsse et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 5 March 2012
                : 14 May 2012
                Page count
                Pages: 6
                Categories
                Research Article
                Medicine
                Cardiovascular
                Atherosclerosis
                Cardiovascular Pharmacology
                Coronary Artery Disease
                Hypertension
                Peripheral Vascular Diseases
                Stroke
                Clinical Research Design
                Drugs and Devices
                Pharmacokinetics
                Drug Absorption
                Drug Distribution
                Drug Excretion
                Drug Metabolism
                Adverse Reactions
                Cardiovascular Pharmacology
                Clinical Pharmacology
                Drug Interactions
                Pharmacodynamics
                Nutrition
                Obesity
                Vitamins
                Toxicology
                Toxic Agents
                Toxin Binding

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                Uncategorized

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