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      An Integrated Proposal to Explain the Epidemic of Cardiovascular Disease in a Developing Country

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          Abstract

          An increase of coronary artery disease has been observed in developing countries during the last years. Various factors may explain this accelerated increase. We propose that inappropriate diet and inadequate sanitary infrastructure may act as triggers to create an imbalance between nitric oxide (NO) and superoxide (O<sup>–</sup><sub>2</sub>). An increase in the concentrations of oxidizedLDL produces both decreased NO and increased O<sup>–</sup><sub>2</sub> endothelial synthesis, by accumulation of asymmetrical N<sup>G</sup>-N<sup>G</sup>-dimethyl- L-arginine, the endogenous inhibitor of NO, and by activation of NAD(P)H oxidase. On the other hand, high rates of chronic infection-inflammation, due to inappropriate sanitary environment stimulate higher circulating levels of proinflammatory cytokines. These cytokines also contribute to reduced NO and increased O<sup>–</sup><sub>2</sub> endothelial production through the same mechanisms of oxidized LDL. The net result of this imbalance is an increased generation of peroxynitrate that injures the endothelium in a proatherogenic, prothrombotic and vasoconstrictive manner.

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          Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994.

          To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.
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            Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension.

            Our aim was to investigate systemic nitric oxide (NO) production and its potential determinants such as insulin resistance, dyslipidemia, and circulating methylated analogs of L-arginine in uncomplicated essential hypertension (EH). Nineteen newly diagnosed, untreated male subjects with mild pure uncomplicated EH and 11 normotensive controls were studied at rest after an overnight fast. The groups had comparable age, body mass index, creatinine clearance, cholesterol, fasting glucose, and insulin. In hypertensives, the urinary excretion rate of nitrite plus nitrate (Unox), an index of endogenous NO production, was depressed (56+/-17 vs. 77+/-23 micromol/mmol creatinine; p < 0.05), whereas plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis, were increased (2.4+/-1.1 vs. 1.1+/-0.7 microM; p < 0.005). Circulating concentrations of symmetric dimethylarginine were similar in both groups (1.4+/-1.3 vs. 1.5+/-1.1 microM; p = NS). The L-arginine-to-ADMA ratio was reduced in hypertension (3.3+/-0.5 vs. 4.5+/-0.8; p < 0.001 for In-transformed data). There was no correlation between Unox and either the magnitude of insulin resistance or dyslipidemia in EH. Thus in male subjects with EH, endogenous systemic NO formation appears depressed, which is unrelated to accompanying insulin resistance or dyslipidemia. Circulating ADMA levels are increased in uncomplicated EH, which may be of potential relevance.
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              Is C-reactive protein an independent risk factor for essential hypertension?

              C-reactive protein (CRP), predicts coronary heart disease incidence in healthy subjects and has been associated with decreased endothelium-dependent relaxation, a potential risk factor for hypertension. However, the relationship between CRP and hypertension has not been studied. To assess whether circulating levels of CRP are independently related to essential hypertension. Cross-sectional population survey. We measured circulating levels of CRP, blood pressure and cardiovascular risk factors among participants. Binomial regression was used to calculate the adjusted effect of CRP on the prevalence of hypertension. General community of Bucaramanga, Colombia. A random sample of 300 subjects > or = 30 years old. Arterial blood pressure. Overall hypertension prevalence was 46.0%. The unadjusted prevalence of hypertension was 58.7% in the highest quartile of CRP, but only 34.7% in the lowest quartile. After adjustment for age, sex, body mass index, family history of hypertension, fasting glycemia, sedentary behaviour, and alcohol consumption, the prevalence of hypertension was 1.14 [95% confidence interval (CI), 0.82, 1.58; P= 0.442], 1.36 (95% CI, 0.99, 1.87; P= 0.057) and 1.56 (95% CI, 1.14, 2.13; P = 0.005) times higher in subjects in the second, third and fourth quartiles of CRP, as compared to subjects in the first quartile. Our results suggest, for the first time, that CRP level may be an independent risk factor for the development of hypertension. However, because of the cross-sectional nature of our study, this finding should be confirmed in prospective cohort studies, aimed at elucidating the role of CRP in the prediction, diagnosis and management of hypertension.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2001
                November 2001
                08 November 2001
                : 96
                : 1
                : 1-6
                Affiliations
                aInstituto Colombiano de Investigaciones Biomédicas, bFundación Cardiovascular del Oriente Colombiano (FCV), cUniversidad Industrial de Santander, and dUniversidad Autónoma de Bucaramanga, Colombia
                Article
                47379 Cardiology 2001;96:1–6
                10.1159/000047379
                11701934
                © 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: 3, Tables: 1, References: 41, Pages: 6
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