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      Lack of Association between Common Polymorphisms in Genes of the Renin-Angiotensin System and Mortality after Myocardial Infarction

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          Abstract

          The insertion/deletion (I/D) polymorphism in the ACE gene and the A1166C polymorphism in the AT1R gene have been associated with left ventricular remodelling and prognosis after acute myocardial infarction (AMI). We investigated whether these genetic variants associate with impaired left ventricular ejection fraction (LVEF) and increased risk for in-hospital mortality after AMI. Consecutive AMI patients were recruited on admission and were genotyped for the above-mentioned polymorphisms. The frequency of the studied genotypes did not differ significantly between deceased patients and those who survived. The LVEF did not differ among patients with or without the DD genotype (45 ± 10 vs. 45 ± 10%, p = 0.892) or the CC genotype (45 ± 10 vs. 46 ± 10%, p = 0.859). These data question the role of the studied genotypes in the pathogenesis of AMI and do not support the previously supported hypothesis that these genotypes influence prognosis after AMI.

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          Most cited references 10

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          Lifestyle and risk factor management and use of drug therapies in coronary patients from 15 countries; principal results from EUROASPIRE II Euro Heart Survey Programme.

            (2001)
          The principal aim of the second EUROASPIRE survey was to determine in patients with established coronary heart disease whether the Joint European Societies' recommendations on coronary prevention are being followed in clinical practice. This survey was undertaken in 1999-2000 in 15 European countries: Belgium, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, the Netherlands, Poland, Slovenia, Sweden, Spain and the U.K., in selected geographical areas and 47 centres. Consecutive patients, men and women or =140 mmHg and/or diastolic blood pressure > or =90 mmHg), 58% had elevated serum total cholesterol (total cholesterol > or =5 mmol x l(-1)) and 20% reported a medical history of diabetes. Glucose control in these diabetic patients was poor with 87% having plasma glucose >6.0 mmol x l(-1)and 72% > or =7.0 mmol x l(-1). Among the patients interviewed the use of prophylactic drug therapies on admission, at discharge and at interview was as follows: aspirin or other antiplatelets drugs 47%, 90% and 86%; beta-blockers 44%, 66% and 63%; ACE inhibitors 24%, 38% and 38%; and lipid-lowering drugs 26%, 43% and 61%, respectively. With the exception of antiplatelet drugs, wide variations in the use of prophylactic drug therapies exist between countries. This European survey of coronary patients shows a high prevalence of unhealthy lifestyles, modifiable risk factors and inadequate use of drug therapies to achieve blood pressure and lipid goals. There is considerable potential throughout Europe to raise the standard of preventive cardiology through more effective lifestyle intervention, control of other risk factors and optimal use of prophylactic drug therapies in order to reduce coronary morbidity and mortality. Copyright 2001 The European Society of Cardiology.
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            A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease.

            In a previous study, men with a history of myocardial infarction were found to have an increased prevalence of homozygosity for the deletional allele (D) of the angiotensin-converting-enzyme (ACE) gene. The D allele is associated with higher levels of ACE, which may predispose a person to ischemic heart disease. We investigated the association between the ACE genotype and the incidence of myocardial infarction, as well as other manifestations of ischemic heart disease, in a large, prospective cohort of U.S. male physicians. In the Physicians' Health Study, ischemic heart disease as defined by angina, coronary revascularization, or myocardial infarction developed in 1250 men by 1992. They were matched with 2340 controls according to age and smoking history. Zygosity for the deletion-insertion (D-I) polymorphism of the ACE gene was determined by an assay based on the polymerase chain reaction. Data were analyzed for both matched pairs and unmatched samples, with adjustment for the effects of known or suspected risk factors by conditional and nonconditional logistic regression, respectively. The ACE genotype was not associated with the occurrence of either ischemic heart disease or myocardial infarction. The adjusted relative risk associated with the D allele was 1.07 (95 percent confidence interval, 0.96 to 1.19; P = 0.24) for ischemic heart disease and 1.05 (95 percent confidence interval, 0.89 to 1.25; P = 0.56) for myocardial infarction, if an additive mode of inheritance is assumed. Additional analyses assuming dominant and recessive effects of the D allele also failed to show any association, as did the examination of low-risk subgroups. In a large, prospectively followed population of U.S. male physicians, the presence of the D allele of the ACE gene conferred no appreciable increase in the risk of ischemic heart disease or myocardial infarction.
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              In-hospital mortality of habitual cigarette smokers after acute myocardial infarction; the "smoker's paradox" in a countrywide study.

              Habitual cigarette smokers, paradoxically, present improved short-term prognosis after acute myocardial infarction, a phenomenon often termed "smoker's paradox". We sought to examine cigarette smokers' post-infarction survival advantage in a countrywide survey of unselected, consecutive patients presenting with acute myocardial infarction. The study population was derived from the registry of the Hellenic study of acute myocardial infarction, which recruited 7433 consecutive patients with acute myocardial infarction from 76, out of a total of 86, hospitals countrywide. Cigarette smokers presented with lower unadjusted mortality rates (7.4% vs 14.5%, P<0.001), were younger, predominantly of male gender and were less likely to suffer from diabetes mellitus and arterial hypertension. When all univariate predictors of poor outcome were included as covariates in multivariate analysis, smoking status was not significantly associated with inhospital mortality (relative risk=1.12, 95% CI=0.86-1.44, P=0.399). The beneficial effect of thrombolytic therapy was independent of the smoking status in both univariate and multivariate analysis. Unadjusted mortality rates are significantly lower in smokers, but age accounted for much of their seemingly improved outcome. When a number of additional clinical variables were taken into consideration, no significant influence of habitual smoking on early outcome following acute myocardial infarction was observed. Copyright 2001 The European Society of Cardiology.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2005
                June 2005
                10 June 2005
                : 103
                : 4
                : 185-188
                Affiliations
                aFirst and bSecond Cardiac Departments, Evangelismos Hospital, cEuroclinic Hospital, and dFirst Cardiac Department of Athens University, Athens, and eCardiac Department, Tzaneion Hospital, Piraeus, Greece; fUniversity of Warwick, Warwick, UK; gHellenic Heart Foundation, Athens, Greece
                Article
                84592 Cardiology 2005;103:185–188
                10.1159/000084592
                15785027
                © 2005 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: 2, Tables: 1, References: 18, Pages: 4
                Categories
                General Cardiology

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