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      Cardiovascular Outcomes in Action to Control Cardiovascular Risk in Diabetes: Impact of Blood Pressure Level and Presence of Kidney Disease

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          Abstract

          Background: Persons with chronic kidney disease (CKD) represent a population prone to cardiovascular disease (CVD) but vulnerable to adverse medication effects. We assessed the impact of intensive antihypertensive therapy on the cerebrovascular and other CVD outcomes in high-risk patients with type 2 diabetes and baseline CKD. Methods: Using current guideline criteria, 1,726 (36.9%) of 4,678 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) arm had mild to moderate CKD (CKD1-3B) at baseline. Participants of this study were randomized to intensive (systolic <120 mm Hg) or standard (systolic <140 mm Hg) BP goals. Fatal and non-fatal stroke were pre-specified secondary outcomes of the ACCORD study. Results: Total cerebrovascular events were significantly higher in participants with baseline CKD (0.66%/year) compared with participants free of CKD (0.28%/year). A significantly higher rate of events was observed in CKD participants. Intensive antihypertensive therapy in participants without CKD at baseline resulted in a 55% significant reduction of any stroke (hazard ratio 0.447; 95% CI 0.227-0.880) and a 50% reduction of non-fatal stroke (hazard ratio 0.498; 95% CI 0.250-0.993). In participants with CKD at baseline, the occurrence of any stroke was reduced by 38% (hazard ratio 0.623; 95% CI 0.361-1.074) and non-fatal stroke by 36% (hazard ratio 0.642; 95% CI 0.361-1.142). Test for interaction was NS between the 2 groups. Changes in other CVD outcomes did not reach statistical significance. Conclusions: These findings suggest that intensive antihypertensive therapy offers significant cerebrovascular protection in diabetic participants without CKD at baseline, but significant benefit to patients with CKD cannot be excluded.

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          Most cited references5

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          Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study.

          Diabetes is regarded as a coronary heart disease risk equivalent-ie, people with the disorder have a risk of coronary events similar to those with previous myocardial infarction. We assessed whether chronic kidney disease should be regarded as a coronary heart disease risk equivalent. We studied a population-based cohort with measures of estimated glomerular filtration rate (eGFR) and proteinuria from Alberta, Canada. We used validated algorithms based on hospital admission and medical-claim data to classify participants with baseline history of myocardial infarction or diabetes and to ascertain which patients were admitted to hospital for myocardial infarction during follow-up (the primary outcome). For our primary analysis, we defined baseline chronic kidney disease as eGFR 15-59·9 mL/min per 1·73 m(2) (stage 3 or 4 disease). We used Poisson regression to calculate unadjusted rates and relative rates of myocardial infarction during follow-up for five risk groups: people with previous myocardial infarction (with or without diabetes or chronic kidney disease), and (of those without previous myocardial infarction), four mutually exclusive groups defined by the presence or absence of diabetes and chronic kidney disease. During a median follow-up of 48 months (IQR 25-65), 11,340 of 1,268,029 participants (1%) were admitted to hospital with myocardial infarction. The unadjusted rate of myocardial infarction was highest in people with previous myocardial infarction (18·5 per 1000 person-years, 95% CI 17·4-19·8). In people without previous myocardial infarction, the rate of myocardial infarction was lower in those with diabetes (without chronic kidney disease) than in those with chronic kidney disease (without diabetes; 5·4 per 1000 person-years, 5·2-5·7, vs 6·9 per 1000 person-years, 6·6-7·2; p<0·0001). The rate of incident myocardial infarction in people with diabetes was substantially lower than for those with chronic kidney disease when defined by eGFR of less than 45 mL/min per 1·73 m(2) and severely increased proteinuria (6·6 per 1000 person-years, 6·4-6·9 vs 12·4 per 1000 person-years, 9·7-15·9). Our findings suggest that chronic kidney disease could be added to the list of criteria defining people at highest risk of future coronary events. Alberta Heritage Foundation for Medical Research. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease.

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              Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study

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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                Am J Nephrol
                S. Karger AG (Basel, Switzerland karger@ 123456karger.com http://www.karger.com )
                0250-8095
                1421-9670
                June 2016
                29 April 2016
                : 43
                : 4
                : 271-280
                Affiliations
                aDepartment of Veterans Affairs Medical Center and bGeorgetown University School of Medicine, Washington, D.C., cDepartment of Veterans Affairs Medical Center, George Washington University, Washington, D.C., dWake Forest School of Medicine, Winston-Salem, N.C., eWFUHS Geriatric/Gerontology, Winston-Salem, Ohio, fUniversity of North Carolina, Chapel Hill, N.C., and gDepartment of Veterans Affairs Medical Center, VA Clinical Center Network, Memphis, Tenn., USA; hMcMaster Medical Center, Hamilton, Ont., Canada
                Article
                AJN2016043004271 Am J Nephrol 2016;43:271-280
                10.1159/000446122
                27161620
                9e6c92cd-d5d6-47d8-90ee-9e44e62e8a9c
                © 2016 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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center. 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
                : 06 April 2016
                : 08 April 2016
                Page count
                Figures: 3, Tables: 3, References: 24, Pages: 10
                Categories
                Original Report: Patient-Oriented, Translational Research

                Medicine,General social science
                Type 2 diabetes mellitus,Chronic kidney disease,Stroke,Hypertension,Intensive antihypertensive therapy

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