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      Association of Chronic Kidney Disease with Preserved Ejection Fraction Heart Failure Is Independent of Baseline Cardiac Function

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          Abstract

          Background/Aims: Chronic kidney disease (CKD) is common among patients with heart failure with preserved ejection fraction (HFpEF) and is associated with worse clinical outcomes. This study aims to identify whether the association of CKD with HFpEF is independent of underlying echocardiographic abnormalities. Materials: We conducted a retrospective cohort study including patients without prevalent heart failure referred for echocardiography. Patients with serial echocardiograms, baseline left ventricular ejection fraction (LVEF) ≥50% and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m<sup>2</sup> were matched 1:1 with patients with eGFR <60 mL/min/1.73 m<sup>2</sup> for age (±5 years), sex, history of hypertension or diabetes, use of renin-angiotensin inhibitors, and LVEF (±5%). A secondary analysis included patients with preserved LVEF and normal left ventricular mass index matched for the same parameters except use of renin-angiotensin inhibitors. Results: Patients with CKD were at increased risk for HFpEF admission: crude hazard ratio (HR) 1.79 (95% confidence interval [CI] 1.38–2.32, p < 0.001) and adjusted HR (for coronary disease, loop diuretics, left atrial diameter) 1.64 (95% CI 1.22–2.21, p = 0.001). LVEF and left ventricular diameter decreased over time in both groups but no difference was observed in rate of dropping. Results were similar in the secondary analysis (crude HR 1.99, 95% CI 1.07–3.71, p = 0.03 and HR adjusted for left atrial diameter 1.98, 95% CI 1.05–3.75, p = 0.04). Rate of change was similar for LVEF, pulmonary artery pressure, and left ventricular mass index in both groups. Conclusion: CKD is independently associated with incident HFpEF despite a similar change in relevant echocardiographic parameters in patients with or without CKD.

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.

            Over the past decade, myocardial structure, cardiomyocyte function, and intramyocardial signaling were shown to be specifically altered in heart failure with preserved ejection fraction (HFPEF). A new paradigm for HFPEF development is therefore proposed, which identifies a systemic proinflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations. The new paradigm presumes the following sequence of events in HFPEF: 1) a high prevalence of comorbidities such as overweight/obesity, diabetes mellitus, chronic obstructive pulmonary disease, and salt-sensitive hypertension induce a systemic proinflammatory state; 2) a systemic proinflammatory state causes coronary microvascular endothelial inflammation; 3) coronary microvascular endothelial inflammation reduces nitric oxide bioavailability, cyclic guanosine monophosphate content, and protein kinase G (PKG) activity in adjacent cardiomyocytes; 4) low PKG activity favors hypertrophy development and increases resting tension because of hypophosphorylation of titin; and 5) both stiff cardiomyocytes and interstitial fibrosis contribute to high diastolic left ventricular (LV) stiffness and heart failure development. The new HFPEF paradigm shifts emphasis from LV afterload excess to coronary microvascular inflammation. This shift is supported by a favorable Laplace relationship in concentric LV hypertrophy and by all cardiac chambers showing similar remodeling and dysfunction. Myocardial remodeling in HFPEF differs from heart failure with reduced ejection fraction, in which remodeling is driven by loss of cardiomyocytes. The new HFPEF paradigm proposes comorbidities, plasma markers of inflammation, or vascular hyperemic responses to be included in diagnostic algorithms and aims at restoring myocardial PKG activity. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              Random-Effects Models for Longitudinal Data

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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2019
                November 2019
                02 September 2019
                : 44
                : 5
                : 1247-1258
                Affiliations
                [_a] aRenal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [_b] bDepartment of Medicine, Geneva University Hospitals, Geneva, Switzerland
                [_c] cDivision of Renal Disease and Hypertension, Department of Internal Medicine, University of Texas Health Science Center, Houston, Texas, USA
                [_d] dDepartment of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [_e] eDepartments of Learning Health Sciences and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
                Author notes
                *Thomas Mavrakanas, Department of Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, CH–1211 Geneva 14 (Switzerland), E-Mail tmavrakanas@gmail.com
                Author information
                https://orcid.org/0000-0002-3368-247X
                Article
                502874 Kidney Blood Press Res 2019;44:1247–1258
                10.1159/000502874
                31476759
                daa513c1-a76a-4fd1-9f11-0ed1cf8272b4
                © 2019 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. 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
                Page count
                Figures: 3, Tables: 4, Pages: 12
                Categories
                Research Article

                Cardiovascular Medicine,Nephrology
                Left ventricular mass index,Left ventricular ejection fraction,Heart failure with preserved ejection fraction,Chronic kidney disease

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