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      Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome

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          Abstract

          The prevalence of heart failure (HF) is increasing. A distinction is made between diastolic HF (preserved left ventricular ejection fraction (LVEF)) and systolic HF (reduced LVEF). Advanced glycation end-products (AGEs) are crystallized proteins that accumulate during ageing, but are particularly increased in patients with diabetes mellitus and in patients with renal failure. Through the formation of collagen crosslinks, and by interaction with the AGE-receptor, which impairs calcium handling and increases fibrosis, AGE-accumulation has pathophysiologically been associated with the development of diastolic and renal dysfunction. Interestingly, diastolic dysfunction is a frequent finding in elderly patients, diabetic patients and in patients with renal failure. Taken together, this suggests that AGEs are related to the development and progression of diastolic HF and renal failure. In this review, the role of AGEs as a possible pathophysiological factor that link the development and progression of heart and renal failure, is discussed. Finally, the role of AGE intervention as a possible treatment in HF patients will be discussed.

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          Chronic kidney disease and mortality risk: a systematic review.

          Marcello Tonelli, Natasha Wiebe, Bruce Culleton … (2006)
          Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.
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            Outcome of heart failure with preserved ejection fraction in a population-based study.

            R Sacha Bhatia, Jack V Tu, Douglas S Lee … (2006)
            The importance of heart failure with preserved ejection fraction is increasingly recognized. We conducted a study to evaluate the epidemiologic features and outcomes of patients with heart failure with preserved ejection fraction and to compare the findings with those from patients who had heart failure with reduced ejection fraction. From April 1, 1999, through March 31, 2001, we studied 2802 patients admitted to 103 hospitals in the province of Ontario, Canada, with a discharge diagnosis of heart failure whose ejection fraction had also been assessed. The patients were categorized in three groups: those with an ejection fraction of less than 40 percent (heart failure with reduced ejection fraction), those with an ejection fraction of 40 to 50 percent (heart failure with borderline ejection fraction), and those with an ejection fraction of more than 50 percent (heart failure with preserved ejection fraction). Two groups were studied in detail: those with an ejection fraction of less than 40 percent and those with an ejection fraction of more than 50 percent. The main outcome measures were death within one year and readmission to the hospital for heart failure. Thirty-one percent of the patients had an ejection fraction of more than 50 percent. Patients with heart failure with preserved ejection fraction were more likely to be older and female and to have a history of hypertension and atrial fibrillation. The presenting history and clinical examination findings were similar for the two groups. The unadjusted mortality rates for patients with an ejection fraction of more than 50 percent were not significantly different from those for patients with an ejection fraction of less than 40 percent at 30 days (5 percent vs. 7 percent, P=0.08) and at 1 year (22 percent vs. 26 percent, P=0.07); the adjusted one-year mortality rates were also not significantly different in the two groups (hazard ratio, 1.13; 95 percent confidence interval, 0.94 to 1.36; P=0.18). The rates of readmission for heart failure and of in-hospital complications did not differ between the two groups. Among patients presenting with new-onset heart failure, a substantial proportion had an ejection fraction of more than 50 percent. The survival of patients with heart failure with preserved ejection fraction was similar to that of patients with reduced ejection fraction. Copyright 2006 Massachusetts Medical Society.
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              ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).

              Kenneth Dickstein, Alain Cohen-Solal, Gerasimos Filippatos … (2008)
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                Author and article information

                Contributors
                : +31-50-3612355 , +31-50-3614391 , a.a.voors@thorax.umcg.nl
                Journal
                Journal ID (nlm-ta): Heart Fail Rev
                Journal ID (iso-abbrev): Heart Fail Rev
                Title: Heart Failure Reviews
                Publisher: Springer US (Boston )
                ISSN (Print): 1382-4147
                ISSN (Electronic): 1573-7322
                Publication date (Electronic): 23 January 2011
                Publication date PMC-release: 23 January 2011
                Publication date (Print): March 2012
                Volume: 17
                Issue: 2
                Pages: 221-228
                Affiliations
                [1 ]Department of Cardiology, University Medical Center Groningen, University of Groningen, 30.001, 9700 RB Groningen, The Netherlands
                [2 ]Department of Laboratory Medicine, Laboratory of metabolic disease, University Medical Center Groningen, Groningen, The Netherlands
                Article
                Publisher ID: 9225
                DOI: 10.1007/s10741-010-9225-z
                PMC ID: 3310987
                PubMed ID: 21259070
                SO-VID: c0961473-8f86-4625-af28-39557f2ac0fb
                Copyright © © The Author(s) 2011
                History
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                Subject: Article
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                issue-copyright-statement © Springer Science+Business Media, LLC 2012

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: advanced glycation end-products,diastolic dysfunction,cardiorenal syndrome,heart failure,renal failure
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: advanced glycation end-products, diastolic dysfunction, cardiorenal syndrome, heart failure, renal failure

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