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      Risk Factors for Sudden Cardiac Death in Patients with Chronic Renal Insufficiency and Left Ventricular Dysfunction

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          Abstract

          Background: Patients with ischemic left ventricular dysfunction have a high risk of sudden cardiac death (SCD). It is, however, unclear if the risk and risk factors of SCD in these patients is modulated by the coexistence of mild chronic renal insufficiency. Methods: We performed a post-hoc analysis of the outcome associated with mild renal dysfunction, as defined by an estimated glomerular filtration rate (eGFR) of <75 ml/min/1.73 m<sup>2</sup> in patients allocated to the conventional medical therapy arm of the Multicenter Automatic Defibrillator Implantation Trial-II. Results: In multivariable analysis, renal dysfunction was independently associated with significant increased risks for all-cause mortality (hazard ratio [HR] = 1.86; 95% CI 1.13–3.05) and SCD (HR = 2.00; 95% CI 1.01–4.02), but not non-SCD, compared to patients without renal dysfunction. Independent predictors of SCD in patients with renal dysfunction were: increased resting heart rate (HR = 2.40; 95% CI 1.50–3.86); low diastolic blood pressure (HR = 3.23; 95% CI 1.52–6.66), and a prolonged QRS duration (HR = 1.63; 95% CI 1.02–2.61). β-Blocker therapy was independently associated with a significant reduction in the risk of SCD in patients with an eGFR of <75 ml/min/1.73 m<sup>2</sup> (HR = 0.61; 95% CI 0.38–0.99). Conclusion: These findings suggest that renal dysfunction significantly increases the risk for SCD in patients with left ventricular dysfunction, and that β-blocker therapy reduces the risk of arrhythmic mortality in heart failure patients with coexisting renal insufficiency.

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          Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.

          We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction. Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction. We retrospectively examined the Studies Of LV Dysfunction (SOLVD) database. Glomerular filtration rate (GFR) was predicted using a recently validated formula. Kaplan-Meier survival analyses were used to compare survival times between groups stratified by level of kidney function (predicted GFR) and hematocrit. Cox proportional-hazards regression was used to explore the relationship of survival time to level of kidney function, hematocrit and their interaction. Lower GFR and hematocrit were associated with a higher prevalence of traditional cardiovascular risk factors. In univariate analysis, reduced kidney function and lower hematocrit, in men and in women, were risk factors for all-cause mortality (p < 0.001 for both). After adjustment for other factors significant in univariate analysis, a 10 ml/min/1.73 m(2) lower GFR and a 1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027 (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that predicted by both factors independently. Decreased kidney function and anemia are risk factors for all-cause mortality in patients with LV dysfunction, especially when both are present. These relationships need to be confirmed in additional studies.
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            Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study.

            Cardiovascular mortality is extremely high in end-stage renal disease. Cardiovascular mortality risk also is increased in selected (high-risk) individuals with mild to moderate impairment of renal function. It is not clear whether a similar association exists in the general population and, if so, through what mechanisms. We investigated the association of renal function with all-cause and cardiovascular mortality in a population-based cohort and explored potential mechanisms underlying any such relationship. An age-, sex-, and glucose-tolerance-stratified sample (N = 631) of a population-based cohort aged 50 to 75 years was followed prospectively. After up to 10.2 years of follow-up, 117 subjects had died (50 of cardiovascular causes). At baseline, renal function was estimated by the serum creatinine level, the Cockcroft-Gault formula and Levey's equation. At baseline, the mean age was 64 +/- 7 years, 48% were men, 55% had hypertension, and 27% (by design) had type 2 diabetes. Serum creatinine was 91.7 +/- 19.0 micromol/L; creatinine clearance as estimated by the Cockroft-Gault formula was 72.5 +/- 13.7 mL/min/1.73 m(2), and the glomerular filtration rate (GFR) estimated by Levey's equation was 67.8 +/- 12.1 mL/min/1.73 m(2). Renal function was inversely associated with all-cause and with cardiovascular mortality. Relative risks (95% confidence intervals) were 1.08 (1.04 to 1.13) and 1.11 (1.07 to 1.16) per 5 micromol/L increase of serum creatinine; 1.07 (0.98 to 1.17) and 1.15 (1.01 to 1.31) for each decrease of 5 mL/min/1.73 m(2) creatinine clearance; and 1.15 (1.05 to 1.26) and 1.26 (1.12 to 1.42) for each decrease of 5 mL/min/1.73 m(2) of GFR. These associations remained after adjusting for age, sex, glucose tolerance status, hypertension, prior cardiovascular disease, low-density lipoprotein cholesterol, homocysteine, (micro)albuminuria, von Willebrand factor, soluble vascular adhesion molecule-1 and C-reactive protein. Analyses in diabetic and hypertensive subjects gave similar results. Mild to moderate loss of renal function is strongly associated with an increased risk of cardiovascular mortality. The mechanism behind this association is unclear but does not appear to involve common risk factors such as hypertension, diabetes or hyperhomocysteinemia. Estimation of renal function by relatively simple methods therefore may be a valuable tool for cardiovascular risk assessment over and above that provided by conventional risk factors. Our results were obtained in a general middle-aged to elderly population, and thus have broad applicability.
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              Level of kidney function as a risk factor for cardiovascular outcomes in the elderly.

              There is a high prevalence of both reduced kidney function as well as cardiovascular disease (CVD) in the elderly. We evaluated whether the level of kidney function is an independent risk factor for CVD outcomes in the Cardiovascular Health Study (CHS), a cohort of subjects whose age at baseline was 65 years old or older. Cox proportional-hazards regression was used to evaluate the association of predicted glomerular filtration rate (GFR) with CVD after adjustment for the major CVD risk factors. We searched for nonlinear relationships between GFR and CVD, as well as interactions between level of kidney function and major CVD risk factors on CVD. A total of 4893 subjects with predicted GFR of 15 to 130 mL/min/1.73 m2 were included in the analysis. Fifty-six percent were female and the mean age was 73.4 years. Of the subjects, 549 (11.2%) died and 1229 (25.1%) experienced CVD events in 5.05 years of follow-up. Each 10 mL/min/1.73 m2 lower GFR was associated with an adjusted hazard ratio for CVD, de novo CVD, recurrent CVD and all-cause mortality of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), 1.04 (0.99, 1.09), and 1.06 (1.00, 1.12), respectively. There was no significant interaction between level of GFR and other traditional CVD risk factors on CVD outcomes. A linear model best described the relationship between GFR and CVD. The level of GFR is an independent risk factor for CVD, de novo CVD, and all-cause mortality in the elderly.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2007
                March 2007
                05 January 2007
                : 27
                : 1
                : 7-14
                Affiliations
                aUniversity of Colorado Health Sciences Center, Denver, Colo., bUniversity of Rochester Medical Center, Rochester, N.Y., and cVeterans Affairs Salt Lake City Healthcare System and University of Utah, Salt Lake City, Utah, USA
                Article
                98431 Am J Nephrol 2007;27:7–14
                10.1159/000098431
                17204832
                © 2007 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: 4, References: 35, Pages: 8
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/98431
                Categories
                Original Report: Patient-Oriented, Translational Research

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