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      The cardiothoracic ratio and all-cause and cardiovascular disease mortality in patients undergoing maintenance hemodialysis: results of the MBD-5D study

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          Abstract

          Background

          The cardiothoracic ratio (CTR) is a non-invasive left ventricular hypertrophy index. However, whether CTR associates with cardiovascular disease (CVD) and mortality in hemodialysis (HD) populations is unclear.

          Methods

          Using a Mineral and Bone disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D Study) subcohort, 2266 prevalent HD patients (age 62.8 years, female 38.0%, HD duration 9.4 years) with secondary hyperparathyroidism (SHPT) whose baseline CTR had been recorded were selected. We evaluated associations between CTR and all-cause death, CVD death, or composite events in HD patients.

          Results

          CTR was associated significantly with various background and laboratory characteristics. All-cause death, CVD-related death, and composite events increased across the CTR quartiles (Q). Adjusted hazard risk (HR) for all-cause death was 1.4 (95% confidential interval, 0.9–2.1) in Q2, 1.9 (1.3–2.9) in Q3, and 2.6 (1.7–4.0) in Q4, respectively (Q1 as a reference). The corresponding adjusted HR for CVD-related death was 1.8 (0.8–4.2), 3.1 (1.4–6.8), and 3.5 (1.6–7.9), and that for composite outcome was 1.2 (1.0–1.6), 1.7 (1.3–2.2), and 1.8 (1.5–2.3), respectively. Exploratory analysis revealed that there were relationships between CTR and age, sex, body mass index, comorbidity of CVD, dialysis duration, dialysate calcium level and intact parathyroid hormone, phosphorus, hemoglobin, and usage of phosphate binder.

          Conclusion

          CTR correlated with all-cause death, CVD death, and composite events in HD patients with SHPT.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s10157-017-1380-2) contains supplementary material, which is available to authorized users.

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          Most cited references39

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          FGF23 induces left ventricular hypertrophy.

          Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.
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            Left ventricular mass monitoring in the follow-up of dialysis patients: prognostic value of left ventricular hypertrophy progression.

            Regression of left ventricular hypertrophy (LVH) in the setting of a well-planned intervention study has been associated with longer survival in hemodialysis patients. Whether changes in left ventricular mass (LVM) in clinical practice predict survival and cardiovascular events in these patients is still unknown. In a prospective study in 161 hemodialysis patients we tested the prognostic value of changes in LVM on survival and incident cardiovascular events. Echocardiography was performed twice, 18 +/- 2 SD months apart. Changes in LVM occurring between the first and the second echocardiographic study were then used to predict mortality and cardiovascular events during the ensuing 29 +/- 13 months. The prognostic value of LVM changes was tested in a multivariate Cox's model with LVM index (LVMI) [expressed as LVM/height(2.71)], included as a covariate to control for regression to the mean. The rate of increase of LVMI was significantly (P= 0.029) higher in patients with incident cardiovascular events than in those without such events. Accordingly, cardiovascular event-free survival in patients with changes in LVMI below the 25th percentile was significantly (P= 0.004) higher than in those with changes above the 75th percentile. In a multiple Cox regression analysis, including age, diabetes, smoking, homocysteine, 1 g/m(2.7)/month increase in LVMI was associated with a 62% increase in the incident risk of fatal and nonfatal cardiovascular events [hazard ratio 1.62 (95% CI 1.13-2.33), P= 0.009]. Changes in LVMI have an independent prognostic value for cardiovascular events and provide scientific support to the use of repeated echocardiographic studies for monitoring cardiovascular risk in dialysis patients.
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              Impact of left ventricular hypertrophy on survival in end-stage renal disease.

              We examined the prognostic significance of left ventricular hypertrophy determined by echocardiography in a cohort beginning renal replacement therapy. No patient had hemodynamically significant valvular disease or echocardiographic signs of obstructive cardiomyopathy. Using the Cox proportional hazards model, left ventricular hypertrophy was significantly associated with survival. The relative risk, based on comparison of upper and lower quintiles of left ventricular mass index, was 3.7 (95% confidence intervals, 1.6 to 8.3) for all-cause mortality and 3.7 (95% confidence intervals, 1.2 to 11.1) for cardiac mortality. The independent risk, adjusted for age, known coronary artery disease, diabetes, level of systolic blood pressure, and treatment (dialysis or transplantation), was 2.9 (95% confidence intervals, 1.3 to 6.9) for all-cause mortality and 2.7 (95% confidence intervals, 0.9 to 8.2) for cardiac mortality. Therefore, left ventricular hypertrophy appears to be an important, independent, determinant of survival in patients receiving therapy for end-stage renal failure.
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                Author and article information

                Contributors
                +81 45 949 7000 , ogatah@med.showa-u.ac.jp
                Journal
                Clin Exp Nephrol
                Clin. Exp. Nephrol
                Clinical and Experimental Nephrology
                Springer Japan (Tokyo )
                1342-1751
                1437-7799
                15 May 2017
                15 May 2017
                2017
                : 21
                : 5
                : 797-806
                Affiliations
                [1 ]ISNI 0000 0004 0443 9643, GRID grid.412812.c, Department of Internal Medicine, , Showa University Northern Yokohama Hospital, ; Chigsaki-chuo 35-1, Tsuzuki, Yokohama, Kanagawa 224-8503 Japan
                [2 ]ISNI 0000 0004 0372 2033, GRID grid.258799.8, Department of Healthcare Epidemiology, Graduate School of Medicine and Public Health, , Kyoto University, ; Kyoto, Japan
                [3 ]Department of Critical Care Medicine, Sakai City Medical Center, Osaka, Japan
                [4 ]Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto, Japan
                [5 ]ISNI 0000 0001 1017 9540, GRID grid.411582.b, Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), , Fukushima Medical University, ; Fukushima, Japan
                [6 ]ISNI 0000 0000 8864 3422, GRID grid.410714.7, Division of Nephrology, Department of Medicine, , Showa University School of Medicine, ; Tokyo, Japan
                [7 ]ISNI 0000 0001 1516 6626, GRID grid.265061.6, Division of Nephrology, Endocrinology and Metabolism, , Tokai University School of Medicine, ; Kanagawa, Japan
                Author information
                http://orcid.org/0000-0002-0046-5575
                Article
                1380
                10.1007/s10157-017-1380-2
                5648748
                28508128
                fe008351-1001-43a7-be28-71306e11693e
                © 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 use, duplication, adaptation, distribution and reproduction in any medium or format, as long as 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.

                History
                : 5 July 2016
                : 4 January 2017
                Categories
                Original Article
                Custom metadata
                © Japanese Society of Nephrology 2017

                Nephrology
                cardiothoracic ratio,cardiovascular disease,ckd-mbd,mbd-5d study,hemodialysis
                Nephrology
                cardiothoracic ratio, cardiovascular disease, ckd-mbd, mbd-5d study, hemodialysis

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