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      Relationship between history of coronary heart disease at dialysis initiation and onset of events associated with heart disease: a propensity-matched analysis of a prospective cohort study

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          Abstract

          Background

          Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD) events, and a number of reports have shown a relationship between CKD and CVD in pre-dialysis or maintenance dialysis patients. However, few studies have reported serial observations during dialysis initiation and maintenance. Therefore, we examined whether the incidence of heart disease events differed between CKD patients with and without a history of coronary heart disease (CHD) at dialysis initiation.

          Methods

          The subjects were patients in the 17 centers participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from October 2011 to September 2013. We excluded nine patients whose outcomes were unknown, as determined by a survey conducted at the end of March 2015. Thus, we enrolled 1,515 subjects into the study. We classified patients into 2 groups according to the history of CHD (i.e., a CHD group and a non-CHD group). Propensity scores (PS) represented the probability of being assigned to a group with or without a history of CHD. Onset of heart disease events and associated mortality and all-cause mortality were compared in PS-matched patients by using the log-rank test for Kaplan-Meier curves. Factors contributing to heart disease events were examined using stepwise multivariate Cox proportional hazards analysis.

          Results

          There were 254 patients in each group after PS-matching. During observation, heart disease events occurred in 85 patients (33.5%) in the CHD group and 48 (18.9%) patients in the non-CHD group. The incidence was significantly higher in the CHD group ( p < 0.0001). The CHD group was associated with higher incidence of heart disease events (vs. the non-CHD group, hazard ratio = 1.750, 95% confidence interval = 1.160–2.639). In addition, comorbidities such as diabetes mellitus, low body mass index, and low serum high-density lipoprotein cholesterol were associated with higher incidence of events.

          Conclusion

          History of CHD at dialysis initiation was associated with a higher incidence of heart disease events and mortality and all-cause mortality.

          Trial registration

          UMIN 000007096. Registered 18 January 2012.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12882-017-0495-8) contains supplementary material, which is available to authorized users.

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          Most cited references15

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          Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.

          The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups. The distribution of estimated GFR was wide and normally shaped, with a mean (+/-SD) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area. The prevalence of coexisting risk factors, prior cardiovascular disease, and a Killip class of more than I was greatest among patients with a reduced estimated GFR (less than 45.0 ml per minute per 1.73 m2), and the use of aspirin, beta-blockers, statins, or coronary-revascularization procedures was lowest in this group. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, congestive heart failure, stroke, or resuscitation after cardiac arrest increased with declining estimated GFRs. Although the rate of renal events increased with declining estimated GFRs, the adverse outcomes were predominantly cardiovascular. Below 81.0 ml per minute per 1.73 m2, each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 (95 percent confidence interval, 1.08 to 1.12), which was independent of the treatment assignment. Even mild renal disease, as assessed by the estimated GFR, should be considered a major risk factor for cardiovascular complications after a myocardial infarction. Copyright 2004 Massachusetts Medical Society
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            Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study.

            Reduced kidney function is a risk factor for cardiovascular morbidity and mortality, and both heart failure (HF) and kidney failure incidences are increasing. This study therefore sought to determine the effect of decreased kidney function on HF incidence in a population-based study of middle-aged adults. From 1987 through 2002, 14,857 participants of the Atherosclerosis Risk in Communities (ARIC) study who were free of prevalent HF at baseline were followed for incident HF hospitalization or death (International Classification of Diseases, Ninth Revision/10th Revision 428/I50). Estimated GFR (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) Study equation, and kidney function was categorized as normal (eGFR > or =90 ml/min per 1.73 m(2); n = 7143), mildly reduced (eGFR 60 to 89 ml/min per 1.73 m(2); n = 7311), and moderately/severely reduced (eGFR or =90 ml/min per 1.73 m(2) (18 versus 6 per 1000 person-years). The overall adjusted relative hazard of developing HF was 1.94 (1.49 to 2.53) for individuals with eGFR <60 ml/min per 1.73 m(2) compared to the reference group and was significantly increased for individuals with and without prevalent coronary heart disease at baseline. A substantially greater decline in kidney function occurred in individuals concomitant with HF hospitalization/death compared to those who did not develop HF. In summary, middle-aged adults with moderately/severely reduced kidney function are at high risk for developing HF.
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              Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study.

              Cardiac disease is a common cause of death in chronic hemodialysis patients. A subanalysis of the data on cardiac diseases in the Hemodialysis (HEMO) Study was performed. The specific objectives were: (1) to analyze the prevalence of cardiac disease at baseline; (2) to characterize the incidence of various types of cardiac events during follow-up; (3) to examine the association of cardiac events during follow-up with baseline cardiac diseases; and (4) to examine the effect of dose and flux interventions on various types of cardiac events. The HEMO Study is a randomized multi-center trial on 1846 chronic hemodialysis patients at 15 clinical centers comprising 72 dialysis units. The scheduled maximum follow-up duration was 0.9 to 6.6 years, with the mean actual follow-up of 2.84 years. The interventions were standard-dose versus high-dose and low-flux versus high-flux hemodialysis in a 2 x 2 factorial design. At baseline, 80% of patients had cardiac diseases, including ischemic heart disease (IHD) (39%), congestive heart failure (40%), arrhythmia (31%), and other heart diseases (63%). There were a total of 1685 cardiac hospitalizations, with angina and acute myocardial infarction accounting for 42.7% of these hospitalizations. There were 343 cardiac deaths during follow-up, accounting for 39.4% of all deaths. IHD was implicated in 61.5% of the cardiac deaths. Any cardiac disease at baseline was highly predictive of cardiac death during follow-up [relative risk (RR) 2.57; 95% CI 1.73-3.83]. There were no significant effects of dose or flux assignments on the primary outcome of all-cause mortality or the main secondary cardiac composite outcome of first cardiac hospitalization or all-cause mortality. Assignment to high-flux dialysis was, however, associated with decreased cardiac mortality and the composite outcome of first cardiac hospitalization or death from cardiac causes. The HEMO Study identified IHD to be a major cause of cardiac hospitalizations and cardiac deaths. Future strategies for the prevention of cardiac diseases in the maintenance hemodialysis population should focus on this entity. Although high-flux dialysis did not reduce all-cause mortality, it might improve cardiac outcomes. This hypothesis needs to be further examined.
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                Author and article information

                Contributors
                +81-562-93-9245 , daijo@fujita-hu.ac.jp
                skoide@fujita-hu.ac.jp
                kazuot@fujita-hu.ac.jp
                h_hiroki460717@yahoo.co.jp
                mhase@fujita-hu.ac.jp
                yukio.kidney@gmail.com
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                28 February 2017
                28 February 2017
                2017
                : 18
                : 79
                Affiliations
                [1 ]ISNI 0000 0004 1761 798X, GRID grid.256115.4, Department of Nephrology, , Fujita Health University School of Medicine, ; Toyoake, Aichi Japan
                [2 ]The Aichi Cohort Study of Prognosis in Patients Newly Initiated Into Dialysis (AICOPP) Group, Aichi, Japan
                Article
                495
                10.1186/s12882-017-0495-8
                5331727
                28245790
                0c5c8444-84b7-4899-bb18-0672a523e19a
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 August 2016
                : 23 February 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Nephrology
                chronic kidney disease,coronary heart disease,dialysis initiation,cardiovascular disease,mortality

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