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      Cardiovascular disease risk factors in chronic kidney disease: A systematic review and meta-analysis

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          Abstract

          Background and objectives

          Chronic kidney disease (CKD) is a global health burden and is independently associated with increased cardiovascular disease risk. Assessment of cardiovascular risk in the general population using prognostic models based on routinely collected risk factors is embedded in clinical practice. In CKD, prognostic models may misrepresent risk due to the interplay of traditional atherosclerotic and non-traditional risk factors. This systematic review’s aim was to identify routinely collected risk factors for inclusion in a CKD-specific cardiovascular prognostic model.

          Design, setting, participants and measurements

          Systematic review and meta-analysis of observational cohort studies and randomized controlled trials. Studies identified from MEDLINE and Embase searches using a pre-defined and registered protocol (PROSPERO ID—2016:CRD42016036187). The main inclusion criteria were individuals ≥18 years of age with non-endstage CKD. Routinely collected risk factors where multi-variable adjustment for established cardiovascular risk factors had occurred were extracted. The primary outcome was fatal and non-fatal cardiovascular events.

          Results

          The review of 3,232, abstracts identified 29 routinely collected risk factors of which 20 were presented in more than 1 cohort. 21 cohorts were identified in relation to 27,465 individuals and 100,838 person-years. In addition to established traditional general population cardiovascular risk factors, left ventricular hypertrophy, serum albumin, phosphate, urate and hemoglobin were all found to be statistically significant in their association with future cardiovascular events.

          Conclusions

          These non-traditional risk factors should be assessed in the development of future cardiovascular prognostic models for use in individuals with CKD.

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          Most cited references36

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          Dangers of using "optimal" cutpoints in the evaluation of prognostic factors.

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            Effect of allopurinol in chronic kidney disease progression and cardiovascular risk.

            Hyperuricemia is associated with hypertension, inflammation, renal disease progression, and cardiovascular disease. However, no data are available regarding the effect of allopurinol in patients with chronic kidney disease. We conducted a prospective, randomized trial of 113 patients with estimated GFR (eGFR) <60 ml/min. Patients were randomly assigned to treatment with allopurinol 100 mg/d (n = 57) or to continue the usual therapy (n = 56). Clinical, biochemical, and inflammatory parameters were measured at baseline and at 6, 12, and 24 months of treatment. The objectives of study were: (1) renal disease progression; (2) cardiovascular events; and (3) hospitalizations of any causes. Serum uric acid and C-reactive protein levels were significantly decreased in subjects treated with allopurinol. In the control group, eGFR decreased 3.3 +/- 1.2 ml/min per 1.73 m(2), and in the allopurinol group, eGFR increased 1.3 +/- 1.3 ml/min per 1.73 m(2) after 24 months. Allopurinol treatment slowed down renal disease progression independently of age, gender, diabetes, C-reactive protein, albuminuria, and renin-angiotensin system blockers use. After a mean follow-up time of 23.4 +/- 7.8 months, 22 patients suffered a cardiovascular event. Diabetes mellitus, previous coronary heart disease, and C-reactive protein levels increased cardiovascular risk. Allopurinol treatment reduces risk of cardiovascular events in 71% compared with standard therapy. Allopurinol decreases C-reactive protein and slows down the progression of renal disease in patients with chronic kidney disease. In addition, allopurinol reduces cardiovascular and hospitalization risk in these subjects.
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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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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 March 2018
                2018
                : 13
                : 3
                : e0192895
                Affiliations
                [1 ] Department of Health Sciences, University of Leicester, Leicester, United Kingdom
                [2 ] John Walls Renal Unit, Leicester General Hospital, University Hospitals of Leicester, Leicester, United Kingdom
                [3 ] Department of Medical Education, University of Leicester, Leicester, United Kingdom
                [4 ] Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom
                Universita degli Studi di Perugia, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-4920-623X
                Article
                PONE-D-17-32218
                10.1371/journal.pone.0192895
                5862400
                29561894
                f5243062-440e-4c4f-81a8-f4dd59706766
                © 2018 Major et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 September 2017
                : 7 January 2018
                Page count
                Figures: 6, Tables: 3, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000291, Kidney Research UK;
                Award ID: TF2/2015
                Award Recipient :
                Dr. Major is generously funded by Kidney Research UK (TF2/2015). Kidney Research UK had no direct role in the study design, collection, analysis and interpretation of data; writing the report; or the final decision to submit the report for publication.
                Categories
                Research Article
                Medicine and Health Sciences
                Nephrology
                Chronic Kidney Disease
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Proteinuria
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Proteinuria
                Medicine and Health Sciences
                Cardiology
                Cardiac Hypertrophy
                Medicine and Health Sciences
                Health Care
                Health Risk Analysis
                Biology and Life Sciences
                Biochemistry
                Lipids
                Cholesterol
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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