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it produces pro-inflammatory cytokines&#46; These cytokines are released to the adjacent myocardium and to the coronary blood flow&#44; in such a way that they have systemic and paracrine effects&#44; influencing the development of coronary atherosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In the general population&#44; EAT has been associated with metabolic syndrome&#44; diabetes mellitus &#40;DM&#41;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;9</span></a> and coronary artery disease &#40;CAD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Mediastinal adipose tissue &#40;MAT&#41; is deposited outside the parietal fascia of the pericardium&#46; The distinction between the different locations of fat deposits is important&#44; since pericardial fat has specific metabolic characteristics and different blood drainage&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;17</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The quantification of EAT is not standardized&#44; the studies are heterogeneous in terms of radiological technique and the location of the fat&#44; and there is no consensus on the reference ranges&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;18</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In patients with advanced CKD or undergoing renal replacement therapy&#44; the volume of EAT has been linked to coronary artery calcification &#40;CaC&#41;&#44; atherosclerosis&#44; inflammation and malnutrition&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;19&#8211;22</span></a> However&#44; there are few data on their predictive ability of CV events and mortality in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The primary objective of our study is to determine whether the quantification of EAT and TMA by multislice synchronized computed tomography &#40;MSCT&#41; is associated with an increase in mortality in patients with advanced CKD &#40;stages 4 and 5&#41; and on hemodialysis&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">As secondary objectives&#44; we explored the association of these parameters with the combined variable of mortality and CV events&#44; the relationship with the CaC score and with biochemical and clinical CV risk factors typical of this population&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">The present study is a <span class="elsevierStyleItalic">post hoc</span> analysis of a prospective and cohort series initially designed to study the capacity of CaC score to predict CV risk&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> The initial study included 137 patients with advanced CKD or on a chronic hemodialysis program&#44; being followed at the Nephrology Unit of the Hospital Universitario Pr&#237;ncipe de Asturias&#46; The inclusion period was 2 years&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The inclusion criteria were&#58; age older than 18 years&#44; advanced CKD &#40;stages 4&#8211;5&#41; and in a hemodialysis program&#44; at least during the 6 months prior to recruitment&#46; The exclusion criteria were&#58; acute renal failure&#44; pregnancy&#44; an intercurrent disease that conditioned an estimated survival of less than 12 months&#44; and the inability to perform an MSCT&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The cases selected had an adequate imaging study available that would allow calculating the thickness of the fatty tissue around the heart in its different locations or grooves&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">All patients signed the informed consent&#46; The study protocol was approved by the local ethics committee&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As part of the routine assessment of patients in the Nephrology Unit&#44; a blood sample was obtained within the month prior to performing an MSCT&#46; Biochemical parameters related to renal function&#44; lipids&#44; bone and mineral metabolism were performed&#46; The time on hemodialysis was defined as the period elapsed since initiation of hemodialysis until the day of the MSCT&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">All included patients had available 16-detector MSCT&#44; Light Speed &#8203;&#8203;Plus GE medical System&#46; Intravenous contrast was not used and the images acquired were reassembled in 2&#8211;3&#160;mm slices&#46; Image processing was carried out on an Advantage Workstation 4&#46;0 console &#40;General Electric&#44; New York&#44; USA&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">An attenuation threshold between &#8211;200 and &#8211;20 Hounsfield units &#40;HU&#41; was used to isolate pericardial fat&#46; The measurement of the thickness of the fatty deposit of interest was defined by manual delineation in millimeters&#44; and following the distribution proposed by other authors&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The total amount of fat in each compartment resulted from the sum of the thickness of the adipose deposit in each groove or region&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8208;</span><p id="par0075" class="elsevierStylePara elsevierViewall">MAT&#58; fatty deposit located in the mediastinum&#44; outside the parietal pericardium &#40;presternal fat&#44; anterior pleural&#44; pleuro-azygoesophageal&#44; paravertebral and cardiophrenic sinuses&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8208;</span><p id="par0080" class="elsevierStylePara elsevierViewall">EAT&#58; visceral fat deposit located intrapericardially and contiguous to the myocardial surface &#40;left and right atrioventricular grooves&#44; interventricular groove&#44; right apex and pericardial thickness or right ventricular free wall&#46;</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">Quantification of the CaC score was determined by the method developed by Agatston&#44; which sets a threshold of 130 HU for determining whether a lesion is calcified&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> CaC scores with a <span class="elsevierStyleItalic">score</span> between 100 and 400 HU indicate moderate atherosclerosis and a relatively high probability of coronary heart disease&#59; CaC values&#62; 400 HU indicate severe atherosclerotic disease&#44; with a high probability of obstructive CAD and a high risk of ischemia&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">To obtain the primary endpoint&#44; incident CV events that caused hospitalization &#40;acute heart failure&#44; acute ischemic heart disease&#44; atrial fibrillation&#44; stroke&#44; and peripheral arterial disease&#41; were recorded&#46; Total mortality and mortality associated with CV events were also registered&#46; Overall survival was defined as the time from the moment of recruitment to the patient&#8217;s death&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0095" class="elsevierStylePara elsevierViewall">Quantitative variables were expressed as means and standard deviation&#44; or median and interquartile range&#44; according to whether data was normally distributed applying the Kolmogorov&#8211;Smirnov test&#46; The categorical variables were expressed as percentages relative to the sample size&#44; unless otherwise specified&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">To perform the analysis of the primary objective&#44; the series was divided into n 2 cohorts of selected cases separated by the cut-off point that determines a higher sensitivity &#40;S&#41; and specificity &#40;E&#41; in the ROC curve for total mortality according to the Youden index&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The 2 groups designed were compared using a Student&#8217;s t-test or Kruskal&#8211;Wallis&#44; as indicated&#46; A multiple regression linear model was also carried out to estimate those variables that were associated with a greater thickness of the adipose tissue defined in the EAT&#46; Pearson or Spearman correlation tests were used to explore the relationship of adipose tissue with the different CV risk variables&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The influence of the defined variables&#44; EAT and MAT&#44; on global mortality and CV events was determined by applying proportional Cox univariate models&#46; The Kaplan&#8211;Meier &#40;KM&#41; method and the Mantel&#8211;Cox method <span class="elsevierStyleItalic">&#40;log-rank test&#41;</span> were applied to compare the cohort survival curves defined by the best cut-off point of EAT&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The data were analyzed using the statistical package version SPSS 20&#46;0 &#40;SPSS Software&#44; Chicago&#44; IL&#44; USA&#41; and R version 3&#46;5&#46;2 &#40;2018&#41;&#59; a level of significance of the p&#160;&#60;&#160;0&#46;05 was established&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0120" class="elsevierStylePara elsevierViewall">The baseline characteristics of the series analyzed are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; There were 104 cases included&#44; 63 patients were on hemodialysis and 41 patients had advanced CKD but not on renal replacement therapy &#40;RRT&#41;&#59; 50&#37; of the cases were women&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">The EAT was greater in hemodialysis patients than with advanced CKD without RRT &#40;17&#46;9&#160;mm &#91;5&#46;27&#93; vs&#46; 13&#46;1&#160;mm &#91;3&#46;98&#93;&#59; p&#160;&#60;&#160;0&#46;001&#41;&#46; The cases with type 2 DM had a greater amount of pericardial adipose tissue than those without type 2 DM&#59; EAT &#40;18&#46;74&#160;mm &#91;6&#46;16&#93; vs&#46; 15&#46;16&#160;mm &#91;4&#46;77&#93;&#59; p&#160;&#61;&#160;0&#46;011&#41; and MAT &#40;59&#46;67&#160;mm &#91;20&#44;88&#93; vs&#46; 52&#46;94&#160;mm &#91;32&#46;65&#93;&#59; p&#160;&#61;&#160;0&#46;018&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Using Youden index&#44; the area under the curve &#40;AUC&#41; for EAT and total mortality was 0&#46;76 &#40;95&#37; CI&#44; 0&#46;66&#8722;0&#46;84&#41;&#59; p&#160;&#60;&#160;0&#46;001 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The cut-off points for EAT to predict total mortality was 11&#46;45&#160;mm &#40;S 92&#46;86&#37;&#59; E 43&#46;75&#37;&#59; positive predictive value &#91;PPV&#93; 65&#46;82&#37;&#59; negative predictive value &#91;NPV&#93; 84&#37; and precision 70&#46;2&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">The AUC for MAT and total mortality was 0&#46;6 &#40;95&#37; CI&#44; 0&#46;49&#8722;0&#46;71&#41;&#59; p&#160;&#61;&#160;0&#46;08&#46; The cut-off point of</p><p id="par0140" class="elsevierStylePara elsevierViewall">MAT to predict total mortality was 55&#46;6&#160;mm &#40;S 44&#46;64&#37;&#59; E 83&#46;33&#37;&#46; PPV 75&#46;76&#37;&#59; NPV 56&#46;34&#37; and precision 62&#46;5&#37;&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The comparison of both AUC curves shows superiority EAT vs&#46; MAT &#40;Z&#160;&#61;&#160;2&#46;44&#59; p&#160;&#61;&#160;0&#46;015&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Patients with a baseline EAT&#160;&#62;&#160;11&#46;45&#160;mm had lower serum albumin levels &#40;4&#46;04&#160;g&#47;dl &#91;0&#46;46&#93; vs&#46; 4&#46;29 &#91;0&#46;31&#93;&#59; p&#160;&#61;&#160;0&#46;018&#41; and a higher CaC score &#40;1&#44;541&#46;95 &#91;1&#44;837&#46;65&#93; vs&#46; 371&#46;24 &#91;631&#46;33&#93;&#59; p&#160;&#60;&#160;0&#46;001&#41;&#46; In this group with EAT&#160;&#62;&#160;11&#46;45&#160;mm there was also a higher prevalence of hypertension&#44; type 2 DM&#44; and a previous history of cardiological events&#46; There were no significant differences in relation to age and gender between the two groups&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The variables that were positively correlated with EAT were&#58; serum level of triglycerides&#44; phosphate and phosphate-calcium product&#46; Serum albumin was negatively correlated with EAT &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; It was not found a correlation with other biochemical parameters&#46; The cardiac history&#44; arterial hypertension and type 2 DM were positively correlated with adipose tissue in the different territories&#46; There was no significant correlation with age or time spent on hemodialysis&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">Linear multiple regression model showed that the variables that could predict a greater EAT thickness were&#58; albumin&#44; CaC <span class="elsevierStyleItalic">score</span>&#44; creatinine&#44; type 2 DM and the previous cardiological event&#44; p&#160;&#60;&#160;0&#46;001&#59; R<span class="elsevierStyleSup">2</span>&#160;&#61;&#160;0&#46;37&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">In addition&#44; the fat tissue measured in different territories was positively correlated with the CaC <span class="elsevierStyleItalic">score&#44;</span> and the correlation was higher with EAT &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; than MAT &#40;&#946;&#160;&#61;&#160;0&#46;39&#44; p&#160;&#60;&#160;0&#46;001 vs&#46; &#160; &#946;&#160;&#61;&#160;0&#46;3&#44; p&#160;&#60;&#160;0&#46;002&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Mortality&#44; CV event and EAT</span><p id="par0170" class="elsevierStylePara elsevierViewall">During a follow-up period of 112&#46;68 &#40;95&#37; CI 109&#46;94&#8211;115&#46;42&#41; months&#44; there were 56 deaths&#46; Of these&#44; 48 patients belonged to the group of highest EAT &#40;&#62;11&#46;45&#160;mm&#41; and 8 patients the fat lower &#40;&#60;11&#44; 45&#160;mm&#41; &#40;&#967;<span class="elsevierStyleSup">2</span> 12&#46;25&#44; p&#160;&#61;&#160;0&#46;001&#41;&#46; According to the KM analysis&#44; patients with EAT thickness&#160;&#62;&#160;11&#46;45&#160;mm had higher mortality than those with lower thickness&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The median survival of patients with EAT&#160;&#60;&#160;11&#46;45&#160;mm was 97&#46;48 months &#40;95&#37; CI&#44; 81&#46;46&#8211;113&#46;51&#41; vs&#46; 76&#46;65 months &#40;95&#37; CI&#44; 66&#46;28&#8211;91&#46;47&#41; in those with EAT&#160;&#62;&#160;11&#46;45&#160;mm&#59; &#967;<span class="elsevierStyleSup">2</span>&#160;&#61;&#160;7&#46;35&#44; p&#160;&#61;&#160;0&#46;007 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">There were 20 deaths due to CV causes&#44; 16 patients had a thickness EAT&#160;&#62;&#160;11&#46;45&#160;mm&#46; The mean survival for CV mortality was 109&#46;11 months &#40;95&#37; CI&#44; 95&#46;59&#8211;122&#46;64&#41; for those with EAT thickness &#60;11&#46;45&#160;mm and 104&#46;57 months &#40;95&#37; CI&#44; 94&#8211;113&#46;8&#41; for EAT&#160;&#62;&#160;11&#46;45&#160;mm &#40;&#967;<span class="elsevierStyleSup">2</span>&#160;&#61;&#160;1&#46;7&#44; p&#160;&#61;&#160;NS&#41;&#46; There was a total of 53 incident CV events that required hospital admission &#40;non-fatal events&#41;&#59; 52&#46;1&#37; occurred in patients with EAT thickness&#160;&#62;&#160;11&#46;45&#160;mm vs&#46; 47&#46;9&#37; with EAT&#160;&#60;&#160;11&#46;45&#160;mm &#40;p&#160;&#61;&#160;NS&#41;&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Analysis of KM for the composite of CV mortality and event was statistically significant &#40;&#967;<span class="elsevierStyleSup">2</span>&#160;&#61;&#160;4&#46;25&#44; p&#160;&#61;&#160;0&#46;039&#41;&#46; While median survival free of any event was 105&#46;04 months &#40;95&#37; CI&#44; 91&#46;1&#8211;118&#46;97&#41; for EAT thickness &#60; 11&#46;45&#160;mm compared to 88&#46;36 months &#40;95&#37; CI&#44; 84&#46;54&#8211;101&#46;57&#41; for EAT&#160;&#62;&#160;11&#46;45&#160;mm &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In the Cox univariate survival analysis&#44; the presence of a thickness EAT&#160;&#62;&#160;11&#46;45&#160;mm was associated with an increased risk of overall mortality&#44; HR 2&#46;28 &#40;95&#37; CI&#44; 1&#46;03&#8211;5&#44; 04&#41;&#44; p&#160;&#61;&#160;0&#46;042&#44; and CV mortality HR 3&#46;01 &#40;95&#37; CI&#44; 0&#46;87&#8211;10&#46;44&#41;&#44; p&#160;&#61;&#160;0&#46;08&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Combined mortality according to CaC score and EAT</span><p id="par0195" class="elsevierStylePara elsevierViewall">The positive correlation observed between the CaC score and the EAT led us to explore whether both variables had statistical power for the group of patients who met the highest risk values for both&#58; CaC <span class="elsevierStyleItalic">score &#62;</span> 400 UH and EAT&#160;&#62;&#160;11&#46;45&#160;mm&#46; Thus&#44; using Cox univariate analysis&#44; it was observed an increase in total and CV mortality with HR values &#8203;&#8203;of 2&#46;11 &#40;95&#37; CI&#44; 1&#46;18&#8211;3&#46;79&#41;&#44; p&#160;&#61;&#160;0&#46;012&#44; and HR 4&#46;4 &#40;95 &#37; CI&#44; 1&#46;09&#8211;17&#46;8&#41;&#44; p&#160;&#61;&#160;0&#46;038&#44; respectively&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Also&#44; the survival analysis shows that nonfatal CV event free mean survival and mean CV mortality &#40;combined&#41; were significant &#967;<span class="elsevierStyleSup">2</span>&#160;&#61;&#160;29&#46;16&#44; p&#160;&#60;&#160;0&#46;001 for the non-affected group <span class="elsevierStyleItalic">&#40;score</span> CaC &#60; 400 UH and EAT&#160;&#60;&#160;11&#46;45&#160;mm&#58; 112&#46;41 months &#91;95&#37; CI&#44; 103&#46;68&#8211;121&#46;14&#41; compared to the group with the affected patients <span class="elsevierStyleItalic">&#40;score</span> CaC &#62; 400 UH and EAT&#160;&#62;&#160;11&#46;45&#160;mm&#41;&#58; 76&#46;09 months &#40;95&#37; CI&#44; 64&#46;22&#8211;87&#46;95&#41; &#40;Appendix supplemental B material&#44; annex&#44; Supplementary Fig&#46; 1A&#41;&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">In the case of total mortality&#44; it remains to be statistically significant &#40;&#967;<span class="elsevierStyleSup">2</span>&#160;&#61;&#160;18&#46;97&#44; p&#160;&#60;&#160;0&#46;001&#41;&#44; with survivals for the unaffected group 96&#46;3 months &#40;95&#37; CI&#44; 84&#46;63&#8211;107&#46;97&#41;&#44; compared to the lower survival rate of the affected group&#58; 69&#46;19 months &#40;95&#37; CI&#44; 57&#46;9&#8211;80&#46;49&#41; &#40;Appendix B supplementary material&#44; annex&#44; Supplementary Fig&#46; 1B&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Mortality&#44; CV event and MAT</span><p id="par0210" class="elsevierStylePara elsevierViewall">The total number of deceased patients with a mediastinal thickness greater than 55&#46;6&#160;mm reached 23&#46;08&#37;&#46; According to the Kaplan&#8211;Meier analysis&#44; patients with a total thickness of MAT&#160;&#62;&#160;55&#46;6&#160;mm had a higher mortality than those with less MAT thickness &#40;&#967;<span class="elsevierStyleSup">2</span>&#160;&#61;&#160;5&#46;85&#44; p&#160;&#61;&#160;0&#46;016&#41; &#40;Appendix Supplementary material&#44; annex&#44; &#40;Fig&#46; 2S-A&#41; This was not the case with mortality and CV events combined &#40;Appendix B Supplementary material&#44; annex&#44; Supplementary Fig&#46; 2&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0215" class="elsevierStylePara elsevierViewall">Various studies in the general population suggest an association between EAT and metabolic syndrome&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;27</span></a> insulin resistance&#44; adiponectin<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and biochemical parameters of inflammation&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;8&#44;10</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">As in other studies&#44; in our series we found that patients with DM and CKD had a higher pericardial fat deposit in all the territories measured compared to patients without DM&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;29</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">In the univariate analysis&#44; we found a negative correlation between serum albumin level and total EAT thickness&#46; Hypoalbuminemia is a component of the inflammation-malnutrition complex&#44; which&#44; in turn&#44; is involved in the etiopathogenesis of CV disease and vascular calcification in patients with advanced CKD and on hemodialysis&#44; which could indicate a possible association between EAT and the inflammation-malnutrition complex observed in these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;30</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Regarding the lipid profile&#44; triglyceride levels could be related to the total thickness of EAT and MAT&#44; but not in the case of total cholesterol&#46; It is important to highlight that in advanced CKD and in hemodialysis the lipid profile different from that of the general population&#46; The total concentration of cholesterol is not as important&#44; as its atherogenic capacity and its density&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">The EAT was positively correlated with the levels of phosphorus&#44; the phospho-calcium product and the CaC <span class="elsevierStyleItalic">score</span>&#46; Vascular calcification is very prevalent in advanced CKD&#46; The main pathogenic factors involved in the generation of vascular calcifications are imbalance in phosphorus and calcium metabolism and chronic inflammation&#46; Hyperphosphatemia and an elevated phospho-calcium product are associated with an increase in mortality and vascular calcification in patients with renal replacement therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;32</span></a> In addition&#44; CaC is more severe and progresses more rapidly in patients with advanced CKD and has been associated with the development of CV events and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#44;34</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">However&#44; the MAT did not correlate with any biochemical parameter of bone mineral metabolism and its association with the CaC score was less intense with the EAT&#46; This result would support the hypothesis that MAT is related to components of the metabolic syndrome<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;10</span></a> and that EAT is mainly related with the development of atherosclerosis and CaC&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17&#44;28&#44;35</span></a> A possible explanation could be the proximity of the EAT with the coronary arteries&#44; which may facilitate a local paracrine inflammatory effect on the coronary endothelium&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;28</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">In the general population&#44; EAT has been associated with fatal and non-fatal coronary events&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;36</span></a> The quantification of EAT could be a predictor of CV risk in patients with CKD or on hemodialysis&#44; but there are few studies in this regard&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;20&#44;23</span></a> In our series&#44; those patients with greater total thickness of EAT and TMA had a higher mortality and a shorter survival free of non-fatal CV events and CV mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;23&#44;37</span></a> More prospective studies would be needed to assess whether the EAT measurement adds any advantage to the CaC <span class="elsevierStyleItalic">score</span> as predictor of mortality&#44; CV risk&#44; and a marker of CAD&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Our study has some limitations&#46; It is a <span class="elsevierStyleItalic">post hoc</span> study&#44; so the results must be considered preliminary and cause-effect relationships cannot be established&#46; There is not a control group available&#46; The sample size is relatively small&#44; so the statistical power is limited and we cannot rule out an association of EAT with other CV risk factors&#46; Lastly&#44; our study is carried out with prevalent hemodialysis patients&#44; and it is well known that the length of stay in renal replacement therapy is associated with an increase in mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> In this sense&#44; having been able to include a sample of incident patients on hemodialysis could have avoided a possible selection bias&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusions</span><p id="par0255" class="elsevierStylePara elsevierViewall">Chronic inflammation and vascular calcification are the main mechanisms involved in the high morbidity and mortality of CKD&#44; being important to obtain markers that allow an early diagnosis of a high CV risk&#46; In patients with advanced CKD or hemodialysis&#44; in addition to the CaC score&#44; the quantification of EAT and TMA by MSCT could be used as a CV prognostic tool&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Financing</span><p id="par0260" class="elsevierStylePara elsevierViewall">The present study has not received any grant&#44; funding or financial support&#46; Availability of data and materials&#46; The data sets used and&#47;or analyzed during the present study are available from the corresponding author&#46; Its availability to third parties will be considered according to current legislation&#44; anonymously&#44; and under individual requests from researchers or working groups&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Ethics approval and consent to participate</span><p id="par0265" class="elsevierStylePara elsevierViewall">The research has been approved by the local ethics committee of the &#8216;Pr&#237;ncipe de Asturias&#8217; University Hospital &#40;dated December 1&#44; 2004&#41;&#46; All participants have signed a consent form specifically designed for current study&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interests</span><p id="par0270" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Key concepts</span><p id="par0275" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8208;</span><p id="par0280" class="elsevierStylePara elsevierViewall">Epicardial fatty tissue is an emerging cardiovascular risk factor&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8208;</span><p id="par0285" class="elsevierStylePara elsevierViewall">In the general population&#44; epicardial fatty tissue has been associated with metabolic syndrome&#44; diabetes mellitus&#44; and coronary artery disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8208;</span><p id="par0290" class="elsevierStylePara elsevierViewall">Epicardial fat tissue could also be a predictor of cardiovascular risk and mortality in patients with advanced chronic kidney disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8208;</span><p id="par0295" class="elsevierStylePara elsevierViewall">Quantification of epicardial fat tissue by multislice synchronized computed tomography could be an additional prognostic tool to estimate cardiovascular risk in this population with advanced chronic kidney disease&#46;</p></li></ul></p></span></span>"
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              "titulo" => "Mortality&#44; CV event and EAT"
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              "identificador" => "sec0030"
              "titulo" => "Combined mortality according to CaC score and EAT"
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              "identificador" => "sec0035"
              "titulo" => "Mortality&#44; CV event and MAT"
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          "titulo" => "References"
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    "fechaRecibido" => "2020-01-01"
    "fechaAceptado" => "2020-09-12"
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          "clase" => "keyword"
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            0 => "Epicardial fat tissue"
            1 => "Chronic kidney disease"
            2 => "Coronary artery calcification"
            3 => "Diabetes mellitus"
            4 => "Cardiovascular disease"
            5 => "Mortality"
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          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Tejido graso epic&#225;rdico"
            1 => "Enfermedad renal cr&#243;nica"
            2 => "Calcificaci&#243;n arterial coronaria"
            3 => "Diabetes mellitus"
            4 => "Enfermedad cardiovascular"
            5 => "Mortalidad"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Epicardial and mediastinal adipose tissue &#40;EAT&#44; MAT&#41; are linked to metabolic syndrome and coronary artery disease&#46; Patients with chronic kidney disease &#40;CKD&#41; have thicker EAT&#46; We assessed if EAT and MAT could be associated with increased mortality and cardiovascular events in patients with advanced CKD and haemodialysis therapy&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">A post-hoc study was performed&#46; We analyzed a prospective series of 104 cases&#46; EAT thickness was quantified by a multislice synchronized computed tomography &#40;MSCT&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The follow-up period was 112&#46;68 &#40;109&#46;94&#8211;115&#46;42&#41; months&#46; The optimal cut-off point of EAT for prediction of total mortality was 11&#46;45&#160;mm &#40;92&#46;86&#37; and 43&#46;75&#37;&#41;&#46; EAT thickness was associated with serum albumin levels&#44; serum triglyceride levels&#44; phosphorus and calcium phosphate product&#46; The EAT was greater in haemodialysis patients compared to those with advanced CKD &#40;P&#160;&#60;&#160;&#46;001&#41;&#46; Patients with diabetes mellitus had greater EAT and MAT thickness &#40;P&#160;&#61;&#160;&#46;018&#41;&#46; At the end of follow up&#44; the survival average time of patients with EAT thickness &#60;11&#46;45&#160;mm was 97&#46;48 months vs&#46; 76&#46;65 months for thickness &#62; 11&#46;45&#160;mm &#40;P&#160;&#61;&#160;&#46;007&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">A higher EAT and MAT thickness was associated with increased mortality&#46; Furthermore&#44; EAT was associated with lower free survival time to fatal and non-fatal cardiovascular events&#46; The measurement of EAT and MAT by MSCT could be a prognostic tool to predict cardiovascular events and mortality risk in advanced CKD patients&#46;</p></span>"
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            "titulo" => "Methods"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivos</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">El tejido graso epicardico &#40;EAT&#41; y mediast&#237;nico &#40;MAT&#41; se relaciona con el s&#237;ndrome metab&#243;lico y la enfermedad arterial coronaria&#46; Los pacientes con enfermedad renal cr&#243;nica &#40;ERC&#41; tienen mayor volumen de EAT&#46; El objetivo de nuestro estudio fue determinar si estos dep&#243;sitos adiposos podr&#237;an estar relacionados con un aumento de mortalidad y eventos cardiovasculares en pacientes con ERC avanzada y en hemodi&#225;lisis&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un an&#225;lisis post hoc de una serie prospectiva&#44; de 104 casos&#44; con una tomograf&#237;a computarizada sincronizada multicorte &#40;MSCT&#41; que permitiera cuantificar el grosor EAT&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">El periodo de seguimiento fue de 112&#44;68 &#40;109&#44;94-115&#44;42&#41; meses&#46; El punto de corte de EAT con mayor sensibilidad y especificidad para predecir mortalidad total fue 11&#44;45 mm &#40;el 92&#44;86 y el 43&#44;75&#37;&#44; respectivamente&#41;&#46; Las variables que se correlacionaron con el EAT fueron la alb&#250;mina&#44; el nivel s&#233;rico de triglic&#233;ridos&#44; de f&#243;sforo y el producto fosfo-c&#225;lcico&#46; El EAT fue mayor en pacientes en hemodi&#225;lisis respecto aquellos con ERC avanzada &#40;p&#160;&#60;&#160;0&#44;001&#41;&#46; Los pacientes con diabetes mellitus ten&#237;an mayor grosor de EAT y MAT &#40;p&#160;&#61;&#160;0&#44;018&#41;&#46; La supervivencia media de los pacientes con EAT &#60; 11&#44;45 mm fue de 97&#44;48 meses vs&#46; 76&#44;65 meses para un grosor &#62; 11&#44;45 mm &#40;p&#160;&#61;&#160;0&#44;007&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Un mayor grosor de EAT y MAT se relacion&#243; con un incremento de mortalidad total&#46; Adem&#225;s&#44; el EAT se asoci&#243; con una menor supervivencia libre de eventos cardiovasculares fatales y no fatales&#46; La cuantificaci&#243;n de EAT y MAT mediante MSCT podr&#237;a tener valor pron&#243;stico para pacientes con ERC avanzada y hemodi&#225;lisis&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as&#58; Cano Meg&#237;as M&#44; Guisado Vasco P&#44; Bouarich H&#44; Lara Aguilera I&#44; de Arriba-de la Fuente G&#44; Rodr&#237;guez-Puyol D&#46; Tejido graso epic&#225;rdico&#44; calcificaci&#243;n arterial coronaria y mortalidad en pacientes con enfermedad renal cr&#243;nica avanzada y hemodi&#225;lisis&#46; Nefrologia&#46; 2021&#59;41&#58;174&#8211;181&#46;</p>"
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            "apendice" => "<p id="par0305" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
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            "titulo" => "Supplementary data"
            "identificador" => "sec0075"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">EAT thickness&#58; cut-off point with the highest sensitivity and specificity in the ROC-global mortality curve&#58; Youden index&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Linear correlation between the EAT and the CaC score &#40;Hounsfield units &#91;HU&#93;&#41;&#44; according to Spearman&#44; rho&#160;&#61;&#160;0&#46;39&#59; p&#160;&#60;&#160;0&#46;001&#46;</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">CaC&#58; coronary artery calcification&#59; EAT&#58; epicardial fatty tissue&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A&#41; Kaplan&#8211;Meier survival curves&#46; Fatal event-free survival according to the cutoff point of 11&#46;45&#160;mm for EAT&#46; B&#41; Mean survival free of non-fatal CV events and CV mortality for EAT&#44; according to the cut-off point of 11&#46;45&#160;mm&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">CV&#58; cardiovascular&#59; EAT&#58; epicardial fat tissue&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">All values &#8203;&#8203;are expressed as their mean &#40;standard deviation&#41;&#44; unless the percentage of individuals is specified&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">CaC score&#58; coronary artery calcification score&#59; HbA1c&#58; glycated hemoglobin&#59; NS&#58; not significant&#59; CRP&#58; C-reactive protein&#59; PTH&#58; parathyroid hormone&#59; UH&#58; Hounsfield units&#46;</p>"
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Triglycerides &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;03&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Phosphorus &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Calcium &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;0&#46;18&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;08&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Calcium-phosphorus product&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Albumin &#40;g&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">CRP &#40;mg&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
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