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      Chronic Kidney Disease Has a Graded Association with Death and Cardiovascular Outcomes in Stable Coronary Artery Disease: An Analysis of 21,911 Patients from the CLARIFY Registry

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          Abstract

          Chronic kidney disease (CKD) is associated with an increased cardiovascular risk in a broad spectrum of populations. However, the risk associated with a reduced estimated glomerular filtration rate (eGFR) in patients with stable coronary artery disease receiving standard care in the modern era, independently of baseline cardiovascular disease, risk factors, and comorbidities, remains unclear. We analyzed data from 21,911 patients with stable coronary artery disease, enrolled in 45 countries between November 2009 and July 2010 in the CLARIFY registry. Patients with abnormal renal function were older, with more comorbidities, and received slightly lower—although overall high—rates of evidence-based secondary prevention therapies than patients with normal renal function. The event rate of patients with CKD stage 3b or more (eGFR <45 mL/min/1.73 m 2) was much higher than that associated with any comorbid condition. In a multivariable adjusted Cox proportional hazards model, lower eGFR was independently associated with a graded increased risk of cardiovascular mortality, with adjusted HRs (95% CI) of 0.98 (0.81–1.18), 1.31 (1.05–1.63), 1.77 (1.38–2.27), and 3.12 (2.25–4.33) for eGFR 60–89, 45–59, 30–44, and <30 mL/min/1.73 m 2, compared with eGFR ≥90 mL/min/1.73 m 2. A strong graded independent relationship exists between the degree of CKD and cardiovascular mortality in this large cohort of patients with chronic coronary artery disease, despite high rates of secondary prevention therapies. Among clinical risk factors and comorbid conditions, CKD stage 3b or more is associated with the highest cardiovascular mortality.

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          Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis.

          Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown. We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2-1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) [vs 95 mL/min per 1·73 m(2)], HR 1·35; 95% CI 1·18-1·55; vs 1·33; 1·19-1·48 and at ACR 30 mg/g [vs 5 mg/g], 1·50; 1·35-1·65 vs 1·52; 1·38-1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts. Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes. US National Kidney Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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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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              Renal function as a predictor of outcome in a broad spectrum of patients with heart failure.

              Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced ( 40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 micromol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR <60 mL/min per 1.73 m2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m2 and 1.86 for <45 mL/min per 1.73 m2 for the primary outcome, both P<0.001, and hazard ratio of 1.50, P=0.006, and 1.91, P=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                18 December 2019
                January 2020
                : 9
                : 1
                : 4
                Affiliations
                [1 ]Université de Paris, Paris, France; emmanuelle.vidal-petiot@ 123456aphp.fr
                [2 ]Physiology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, 75018 Paris, France
                [3 ]Institut nationale de la santé et de la recherché médicale (INSERM) U1149, Centre de Recherche sur l’Inflammation, 75018 Paris, France
                [4 ]Robertson Centre for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK; Nicola.Greenlaw@ 123456glasgow.ac.uk (N.G.); Ian.Ford@ 123456glasgow.ac.uk (I.F.)
                [5 ]Portsmouth Hospitals NHS Trust, Portsmouth PO6 3LY, UK; paulkalra@ 123456doctors.org.uk
                [6 ]Hospital Santa Creu i Sant Pau, 08041 Barcelona, Spain; XGarcia-Moll@ 123456santpau.cat
                [7 ]Montreal Heart Institute, Université de Montreal, Montreal, QC H1T1C8, Canada; Jean-Claude.Tardif@ 123456icm-mhi.org
                [8 ]University Hospital Ramon y Cajal, 28040 Madrid, Spain; zamorano@ 123456secardiologia.es
                [9 ]Centro Cardiologico Universitario di Ferrara, University of Ferrara, 44124 Cona, FE, Italy; roberto.ferrari@ 123456unife.it
                [10 ]Maria Cecilia Hospital, GVM Care & Research, 48033 Cotignola, RA, Italy
                [11 ]Department of Cardiology and Structural Heart Disease, School of Medicine in Katowice, Medical University of Silesia, 40-055 Katowice, Poland; michal.tendera@ 123456gmail.com
                [12 ]National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London SW3 6NP, UK; kim.fox@ 123456imperial.ac.uk
                [13 ]Cardiology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, French Alliance for Cardiovascular Trials, INSERM U1148, 75018 Paris, France
                Author notes
                [* ]Correspondence: gabriel.steg@ 123456aphp.fr ; Tel.: +331-40-25-86-68; Fax: +331-40-25-88-65
                [†]

                A list of the CLARIFY Investigators is included in the Supplement.

                Author information
                https://orcid.org/0000-0001-9356-7302
                https://orcid.org/0000-0002-0812-6113
                https://orcid.org/0000-0001-6896-2941
                Article
                jcm-09-00004
                10.3390/jcm9010004
                7019870
                31861379
                dff654e8-a13d-4249-aa58-9799226f3746
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 November 2019
                : 13 December 2019
                Categories
                Article

                chronic kidney disease,chronic coronary artery disease,clarify registry

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