Clinical Study Independent Value of Cardiac Troponin T and ...

Clinical StudyIndependent Value of Cardiac Troponin T andLeft Ventricular Global Longitudinal Strain in PredictingAll-Cause Mortality among Stable Hemodialysis Patients withPreserved Left Ventricular Ejection Fraction

Junne-Ming Sung1 Chi-Ting Su2 Yu-Tzu Chang1 Yu-Ru Su3

Wei-Chuan Tsai1 Saprina P H Wang1 Chun-Shin Yang4 Liang-Miin Tsai1

Jyh-Hong Chen1 and Yen-Wen Liu1

1 Division of Nephrology and Cardiology Department of Internal Medicine College of Medicine and HospitalNational Cheng Kung University 138 Sheng-Li Road Tainan 704 Taiwan

2Department of Human Genetics Graduate School of Public Health University of Pittsburgh Pittsburgh PA USA3 Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA4Division of Nephrology Department of Internal Medicine Catholic Fu-An Hospital Yun-Lin Taiwan

Correspondence should be addressed to Junne-Ming Sung jmsungmailnckuedutw and Yen-Wen Liu wen036030gmailcom

Received 7 February 2014 Accepted 5 April 2014 Published 7 May 2014

Academic Editor Michael Gotzmann

Copyright copy 2014 Junne-Ming Sung et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Using a speckle-tracking echocardiography (STE) we recently demonstrated that a left ventricular (LV) global longitudinal strain(GLS) ge minus15 and the serum cardiac troponin T (cTnT) concentration are associated withmortality in stable hemodialysis patientswith preserved LV ejection fraction (LVEF) In this study we explored the relationship between cTnT and echocardiographicparameters and evaluated whether the prognostic value provided by cTnT is independent of a GLS ge minus15 and vice versa Eighty-eight stable hemodialysis patients with preserved LVEF were followed for 31 months STE studies and measurements of cTnTwere performed at baseline CTnT concentration had a modest correlation with GLS (119903

119904= 044 119875 lt 0001) but had a weak

or nonsignificant correlation with other echocardiographic parameters Adjusting for clinical parameters hazard ratios for eachincrease of 001 ngmL in cTnT and a GLS ge minus15 on mortality were 113 (119875 = 0009) and 309 (119875 = 003) without significantinteraction between cTnT and GLS ge minus15 In addition an increased cTnT concentration a GLS ge minus15 or their combinationshowed significant additional predictive value for mortality when included in models consisting of clinical parameters Thereforeboth cTnT and a GLS ge minus15 are independent predictors of mortality and are useful for risk stratification

1 Introduction

Mortality in patients with end-stage renal diseases (ESRDs)remains high mainly because of their high cardiovasculardisease burden [1ndash3] The kidney disease outcome qualityinitiative (KDOQI) guidelines recommend that conventionalechocardiography should be performed at the initiation ofdialysis and every 3 years thereafter in all ESRD patientsfor cardiac risk stratification and optimization of therapies

[4ndash7] However hemodialysis patients with heart failure(HF) andor overt systolic dysfunction defined by low leftventricular (LV) ejection fraction (LVEF) on conventionalechocardiography have very poor outcome [4ndash6 8 9] andfrequently respond poorly to therapies [10] It is thus feasiblethat early identification of high-risk patients in an asymp-tomatic and stable hemodialysis population with preservedLVEFmay facilitate an early initiation of therapies to improveoutcome

Hindawi Publishing CorporationBioMed Research InternationalVolume 2014 Article ID 217290 12 pageshttpdxdoiorg1011552014217290

2 BioMed Research International

For early detection of subclinical heart disease two-dimensional speckle-tracking echocardiography (STE) withmyocardial deformation (2D strain) analysis and themeasur-ing of serum cardiac biomarkers such as cardiac troponinT (cTnT) may be useful tools STE with 2D strain analysisis a quantitative method for the assessment of subtle LVdysfunction which cannot be evaluated by semiquantita-tive conventional echocardiography [11ndash16] Using 2D strainanalysis LV global peak systolic longitudinal strain (GLS)or circumferential strain (CS) is the ratio of the maximalchange in myocardial longitudinal or circumferential lengthin systole to the original length respectively During systolethe LV myocardium shortens in either direction thereforeGLS or CS has a negative value and less negative GLS orCS value indicates poorer global LV systolic function [13 16]GLS has been demonstrated to be a more sensitive predictorfor all-cause mortality than LVEF in the general population[17] We recently reported that a less negative GLS (definedas GLS ge minus15 ie an absolute value of GLS le 15) butnot LVEF predicted all-cause and cardiac mortality amongstable hemodialysis patients with preserved LVEF (LVEF ge50) indicating that GLS is a promising marker for earlyrisk stratification [18] As for serum cardiac biomarker highcirculating cTnT concentrations are associated with highmortality in dialysis patients [2 19 20] The food and drugadministration and the KDOQI guidelines [7] both indicatethe use of cTnT as a biomarker formortality risk stratificationin dialysis patients In our previous study we also foundthat the elevated cTnT concentration correlated with GLSand is associated with high mortality in this hemodialysispopulation [18]

Validation of a novel marker for risk stratification in aspecific population requires a phased approach Early-phasestudies should demonstrate that the novel marker is associ-ated with the outcome Midphase studies should explore therelationships between various markers and demonstrate thatthe new marker provides additional value beyond traditionaland other markers in identifying high-risk patients andorchanging the decision-making process The relationshipbetween cTnT concentrations and conventional echocardio-graphic parameters has been extensively studied in a generaldialysis population [2 19ndash21] however the relationshipbetween cTnT concentrations and subtle LV dysfunction andclinical characteristics in stable hemodialysis patients withpreserved LVEF is still unclear though we have noted thatthe cTnT concentration correlated with GLS in our previousstudy [18] Furthermore because cTnT might correlate withGLS it raises a question of whether the association of cTnTwith mortality remains significant after adjustment for otherprognostic factors including GLS In other words whethercTnT can replace GLS in risk stratification or vice versais still unknown In addition it remains unclear whetherthere is an additional prognostic value of cTnT or a GLSge minus15 or their combination beyond other prognosticfactors In this study we explored the relationships betweencTnT concentrations and patientsrsquo characteristics and STE-measured echocardiographic parameters and evaluated theadditional prognostic value provided by cTnT or a GLS geminus15 or their interaction to define their clinical usefulness

2 Subjects and Methods

21 Patients This study adhered to the Declaration ofHelsinki and all enrolled patients provided written informedconsent The study protocol was approved by the HumanResearch andEthicsCommittee of our institute (IRBnumberER-98-073) As previously described [18] from December2008 to January 2009 adult stable hemodialysis patients (ge18years old) receiving a maintenance hemodialysis programconsisting of 4 hours a session thrice weekly for more than3 months were prospectively enrolled from two communityhospitals in Yun-Lin County Taiwan National Cheng KungUniversity Hospital Dou-Liou Branch and Catholic Fu-AnHospital In total 120 hemodialysis patients without intercur-rent or terminal illnesses were screened and 109 patients wereincluded (3 with starting long-term hemodialysis lt3 monthsand 8 without the willingness to participate) Additionalpatients were subsequently excluded because of old age (ge80years 119899 = 3) LVEF lt50 (119899 = 2) or episodic or persistentHF (geNYHA FC III) [22 23] within 6 months (119899 = 3)Patients with chronic atrial fibrillation (119899 = 4) recentinfarction (119899 = 1) severe valvular heart disease (119899 = 2) orinadequate image quality (119899 = 6) were also excluded The 88enrolled patients were followed for 31 months or until deathUpon enrollment and during the follow-up period clinicalinformation on comorbidities medical history and cardio-vascularmedicationwere obtained by a careful review of eachpatientrsquos medical record andor a self-reported questionnaireThe primary outcome was all-cause mortality

22 Biochemical Measurements Blood was collected beforethe midweek dialysis session in the same week that theechocardiographic study was performed Sera were stored atminus80∘C until analysis when they were thawed for measure-ment of the concentrations of cTnT (4th generation TroponinT STAT immunoassay ElecSys 2010 System Roche Diag-nostics Indianapolis IN USA) high-sensitivity C-reactiveprotein (BN II analyzer Dade Behring Glasgow DE USA)interleukin-6 (chemiluminescent sandwich ELISA Quan-tikine Human interleukin-6 RampD Systems Inc Minneapo-lis MN USA) and procollagen type I C-terminal peptide(Takara Bio Inc Otsu Shiga Japan) The measurements ofcTnT concentrationwere performed in the clinical laboratoryat National Cheng-Kung University Hospital and were super-vised by one of the coauthors (YWL) CTnT concentrationswere assayed in batch using the automated ElecSys 2010analyzer The lower limit of detection for this assay is001 ngmL which also reflects the 99th percentile cutoff limitfor detection of myocardial necrosis In our laboratory thecoefficient of variation (CV) at 0078 ngmL is 50 and theCV at 2300 ngmL is 25 Serum cholesterol triglyceridescalcium phosphate and albumin were measured using anautomatic analyzer

23 Echocardiographic Measurements All patients wereexamined by one well-trained cardiologist (YWL with 10years of experience in echocardiographic examination) usingan ultrasound system with a 35MHz probe (Vivid-i GE

BioMed Research International 3

Table 1 Baseline clinical characteristics of stable hemodialysis patients with preserved left ventricular ejection fraction

cTnT Tertiles119875 for trendLower

(cTnT le 002 ngmL119899 = 30)

Middle(002 lt cTnT le 0042 ngmL

119899 = 29)

Upper(cTnT gt 0042 ngmL119899 = 29)

Age (years) 640 plusmn 130 679 plusmn 87 684 plusmn 116 027Male 119899 () 11 (37) 9 (31) 12 (42) 071BMI (kgm2) 213 plusmn 30 226 plusmn 25 212 plusmn 29 015Ktv 175 plusmn 022 171 plusmn 024 166 plusmn 022 030IDWG (kg) 263 plusmn 083 292 plusmn 102 278 plusmn 125 060IDWG () 51 plusmn 18 52 plusmn 16 51 plusmn 23 098Hemodialysis duration (years) 65 (4 9) 44 (2 99) 4 (18 64) 031SBP (mmHg) 1430 plusmn 132 1522 plusmn 163 1441 plusmn 152 093DBP (mmHg) 739 plusmn 87 810 plusmn 78 762 plusmn 102 044Heart rate 747 plusmn 114 758 plusmn 124 755 plusmn 126 094Prevalent CAD 8 (27) 11 (38) 12 (41) 046Diabetes mellitus 7 (23) 16 (55) 22 (76) lt0001lowast

Hypertension 27 (90) 25 (86) 25 (86) 085LV hypertrophy 28 (93) 27 (93) 27 (93) 095ACEIARB 17 (57) 18 (62) 13 (45) 040120573-Blocker 15 (50) 11 (38) 15 (52) 040CCB 15 (50) 17 (59) 18 (62) 048Statin 6 (20) 4 (14) 5 (17) 094Calcium (mgdL) 94 plusmn 09 91 plusmn 07 92 plusmn 07 026Phosphate (mgdL) 44 plusmn 13 48 plusmn 13 41 plusmn 11 019Albumin (gdL) 33 plusmn 05 34 plusmn 03 32 plusmn 04 021Cholesterol (mgdL) 1631 plusmn 357 1686 plusmn 415 1576 plusmn 357 055hsCRP (mgdL) 026 (014 063) 066 (018 099) 045 (019 195) 012IL-6 (pgmL) 95 (73 163) 97 (69 137) 106 (63 191) 085PICP (ngmL) 8436 plusmn 3985 8021 plusmn 3318 9528 plusmn 4449 034Continuous data are expressed as the mean plusmn standard deviation or the median (25th and 75th percentiles) categorical data are expressed as the number(percentage) A nonparametric Kruskal-Wallis test was used for nonnormally distributed datalowast

119875 lt 005 LV hypertrophy was diagnosed by echocardiographyAbbreviations ACEI angiotensin-converting enzyme inhibitor ARB angiotensin II-receptor blocker BMI body mass index CAD coronary artery diseaseCCB calcium channel blocker cTnT cardiac troponin T DBP diastolic blood pressure hsCRP high-sensitivity C-reactive protein IDWG interdialytic weightgain IL interleukin KtV an indicator of dialysis adequacy (119870 urea clearance 119905 dialysis time119881 urea distribution volume) LV left ventricle PICP procollagentype I C-terminal peptide SBP systolic blood pressure

Healthcare Horten Norway) Two-dimensional STE andtissue Doppler imaging (TDI) were performed as previouslydescribed [15 16 18] All participants received an echocardio-graphic examination at the halfway point of the hemodialysissession (the second or third hour of each session) [18] Wemeasured LVMi LV volume LVEF and left atrial volumeindex and LV hypertrophy (LVH) was defined as an LVMigt115 gm2 for men and gt95 gm2 for women [22ndash24]

Using pulsed-wave Doppler we measured the peak early(E)-wave and late (A)-wave velocities of the mitral inflowThe pulse TDI of the mitral annulus movement was acquiredfrom the apical 4-chamber view when a sample volume wasplaced first at the septal side and then at the lateral side ofthe mitral annulus To obtain the peak systolic (1199041015840) and earlydiastolic (1198901015840) velocities we measured 3 end-expiratory beatsand averaged these values for further analysis We used the

average 1198901015840 velocity acquired from the septal and lateral sidesof themitral annulus to calculate the ratio of themitral inflow119864 to the 1198901015840 velocity (average 1198641198901015840 = 119864[(1198901015840septal + 119890

1015840

lateral)2])We acquired 2D gray-scale STE images in the 3 standardapical views (ie apical 4-chamber apical 2-chamber andapical long-axis) for 3 cardiac cycles and then stored theimages digitally for subsequent off-line analysis To evaluatethe fluid status we measured the IVC diameter twice with anaverage value defined as the IVCe at the end of expirationin a subxiphoid location and just proximal to the junctionof the hepatic veins [16 22 23 25] IVCe gt 153 cm indicateshypervolemia in ESRD patients [16 25]

24 2D Strain Analysis Off-line 2D strain analysis wasperformed using automated functional imaging software(EchoPAC work station BT09 GE Healthcare Israel) Peak


10

08

06

04

02

00

0 10 20 30 40

Low cTnT groupMiddle cTnT group

High cTnT group

Cum

surv

ival

Follow-up duration (months)

Log rank P = 0003

(a)

06

04

02

00

0 10 20 30 40


cTnT gt 0042ngmL

cTnT le 0042ngmLCum

haz

ard

uarr 285X

P = 0001

cTnT gt 0042

cTnT le 0042ngmL

(b)

Figure 1 (a) The Kaplan-Meier estimates of the overall survival probability of patients stratified by tertiles of cTnT concentrations (b) TheKaplan-Meier estimates of the cumulative hazard rate for all-cause mortality stratified by the cTnT concentration with a cutoff of 0042 ngdL(the lower limit of the upper tertile) with a hazard ratio (HR) of 285 (95 confidence interval [CI] 144ndash562 119875 = 0001) for cTnT gt 0042

systolic longitudinal strain was automatically obtained fromthe 3 standard apical views The average peak systolic lon-gitudinal strain value from the 3 apical views was regardedas the GLS Six LV segments on the parasternal short-axisview at the midpapillary level were examined to obtain thesegmental circumferential strains in systole and the averageof these 6 segmental circumferential strain was defined as theCS [16 18] The Bland-Altman analysis revealed no systemicbias of the GLS between intra- and interobserver agreements[18] In addition hemodialysis per se did not affect GLSmeasurement [18]

25 Statistical Analysis Continuous data are presented as themean plusmn standard deviation or the median and interquartilerange depending on the distribution Dichotomous data arepresented as numbers and percentages We stratified patientsby tertiles of the cTnT concentration and comparisons amonggroups across the tertiles were performed using the trend testA Kruskal-Wallis test was used for nonnormally distributeddata The Kaplan-Meier method with a log-rank test wasused to compare mortality between strata The relationshipsamong continuous variables were evaluated using a Pearsoncorrelation or a Spearmanrsquos correlation analysis dependingon the distribution Uni- and multivariate Cox regressionanalysis were used to examine the risk factors for all-causemortality We confirmed that all variables considered inthe regression analysis met the assumption of proportionalhazards The additional predictive value of cTnT concentra-tions and a GLS ge minus 15 for mortality was investigatedusing a multivariate Cox regression with analysis of thedeviance between different models and a receiver operatingcharacteristic (ROC) curve analysis A 119875 lt 005 was con-sidered statistically significant All statistical analyses were

performed using SAS software version 92 (SAS Institute) orSPSS (Statistical Package for the Social Sciences) softwareversion 170 (SPSS Inc)

3 Results

This was a prospective study of 88 stable hemodialysispatients with preserved LVEF (LVEF ge 50) All patientspresented with anuria and received adequate hemodialysis(average KtV 171 plusmn 023 hemoglobin 102 plusmn 12mgdL)[26] The baseline characteristics and echocardiographicparameters in the all enrolled patients had been reported ina previous study [18] Patients were stratified by tertiles basedon their cTnT concentrations lower (cTnT le 002 ngmL)middle (002 lt cTnT le 0042 ngmL) and upper tertiles(cTnT gt 0042 ngmL) Comparisons of baseline character-istics across tertiles of cTnT concentrations are listed inTable 1 The prevalence of diabetes was significantly differ-ent across tertiles but not background CAD hypertensionand LVH Other variables were not significantly differentacross tertiles Comparisons of baseline LV geometric andfunctional parameters across tertiles of cTnT concentrationswere listed in Table 2 Only LV-GLS showed a significantdifference across tertiles other variables including LV massindex (LVMi) LV diastolic functional parameters and otherLV systolic parameters did not There was no significantdifference in LV end-diastolic volume index (LVEDVi) orend-expiratory inferior vena cava diameter (IVCe) acrosstertiles and the IVCe did not increase in the patients of eachgroup indicating that the volume status of patients in thesethree groups was similar and that substantial hypervolemiadid not occur [16 27] In total 82 patients (93) presentedLVH [22] and all three groups presented an inverse ratio


Table 2 Baseline echocardiographic study of asymptomatic hemodialysis patients with preserved left ventricular ejection fraction

cTnT Tertile119875 for trendLower

(cTnT le 002 ngmL 119899 = 30)

Middle(cTnT of 002ndash0042 ngmL

119899 = 29)


LV EDVi (mLm2) 699 plusmn 188 695 plusmn 208 711 plusmn 193 096LVMi (gmm2) 1354 plusmn 250 1515 plusmn 572 1591 plusmn 647 027IVCe diameter (cm) 121 plusmn 026 13 plusmn 021 135 plusmn 035 018LVEF () 657 plusmn 52 647 plusmn 59 623 plusmn 64 0101199041015840 (cmsec) 87 plusmn 20 88 plusmn 16 79 plusmn 22 016GLS () minus200 plusmn 35 minus176 plusmn 30 minus164 plusmn 46 0002lowast

LSRs (secminus1) minus102 plusmn 021 minus098 plusmn 022 minus089 plusmn 021 006CS () minus222 plusmn 56 minus207 plusmn 63 minus196 plusmn 59 033CSRs (secminus1) minus205 plusmn 056 minus198 plusmn 066 minus166 plusmn 045 005119864 (msec) 079 plusmn 031 081 plusmn 031 079 plusmn 029 097119860 (msec) 101 plusmn 028 109 plusmn 039 100 plusmn 027 053119864119860 085 plusmn 053 080 plusmn 035 078 plusmn 023 0781198901015840 (cmsec) 50 plusmn 14 48 plusmn 11 47 plusmn 15 0631198641198901015840 158 plusmn 59 182 plusmn 101 168 plusmn 61 052LAVi (mLm2) 341 plusmn 79 356 plusmn 77 364 plusmn 89 067Continuous data are expressed as the mean plusmn standard deviation or the median (25th and 75th percentiles) categorical data are expressed as the number(percentage) A nonparametric Kruskal-Wallis test was performed for nonnormally distributed datalowast

119875 lt 005Abbreviations CS average circumferential strain CSRs circumferential systolic strain rate cTnT cardiac troponin T EDVi end-diastolic volume indexEF ejection fraction 1198641198901015840 early transmitral velocity to tissue Doppler mitral annular early diastolic velocity ratio GLS global left ventricular peak systoliclongitudinal strain IVCe end-expiratory inferior vena cava diameter LAVi left atrial volume index LSRs longitudinal systolic strain rate LV left ventricularLVMi left ventricular mass index 1199041015840 left ventricular systolic myocardial velocity

between early and late LV filling velocity a high 1198641198901015840 anda high left atrial volume index (LAVi) indicating that mostpatients in this cohort had LVH and diastolic dysfunction

There were different degrees of correlations among theechocardiogram parameters LVMi LVEF GLS systolic lon-gitudinal strain rates (LSRs) CS and systolic circumferentialstrain rates (CSRs) (see Table S1 in Supplementary Mate-rial available online at httpdxdoiorg1011552014217290)Because the distribution of cTnT was skewed (skewness= 098) we assessed the relationships between cTnT andechocardiographic parameters using Spearmanrsquos correlation(Table 3) CTnT concentrationsmodestly correlatedwithGLS(119903119904= 044 119875 lt 0001) and weakly correlated with LVEF

LSRs CS and CSRs (all |119903119904| lt 03 and all 119875 lt 005) Other

variables including LVMi LVEDVi IVCe and diastolicfunctional indicators hadno significant correlationwith cTnTconcentrations

During the follow-up of 31 months 24 patients (273)died 9 from cardiovascular death 11 from infections and4 from liver disease [18] The baseline median plasma cTnTconcentrations were significantly higher in patients who diedthan in those who survived to the end of 31-month follow-up (0049 [25th 75th percentiles 0023 0134] versus 0025[0010 0042] 119875 = 0001) Figure 1(a) illustrates the Kaplan-Meier estimates of the overall survival probability of patientsstratified by tertiles of cTnT concentrations Figure 1(b) showsthe Kaplan-Meier estimates of the cumulative hazard rate for

mortality stratified by the cTnT concentration with a cutoffof 0042 (the lower limit of the upper tertile) with a hazardratio (HR) of 285 (95 confidence interval [CI] 144ndash562119875 = 0001) for cTnT gt 0042The results of the univariate Coxregression analysis for mortality are listed in Table S2 Basedon our previous study [18] and a recentmeta-analysis [28] weused aGLS ofminus15 and a CS of minus233 as cutoff values in thisanalysis In addition because the plasma values of cTnT werelow and an increase of 001 in the cTnT concentration maybe clinically significant we multiplied the cTnT values by 100(cTnT times 100) for analysis For the multivariate Cox regressionanalysis a background of CAD diabetes and hypertensiontogether with plasma albumin concentration which were sig-nificant predictors in the univariate analysis were selected tobe basic clinical parameters and to construct the basic model(Table 4) Because the cTnT concentrations were modestlycorrelated with GLS we first observed the changes in HRwhen adding cTnT times 100 and GLS ge minus15 individually orconcomitantly in the basicmodelWeobservedno substantialchange in HR of cTnT times 100 and GLS ge minus15 Furthermorethere was no significant interaction between cTnT times 100 anda GLS ge minus15 in the full model (Table 4) indicating thatcTnT and a GLS ge minus15 are independently associated withmortality After adjustment for basic clinical parameters theHRs associatedwith an increase of 001 in cTnT concentrationand aGLSge minus15 in relation tomortality were 113 (103ndash124119875 = 0009) and 309 (114ndash843 119875 = 003) respectively


Table 3 Spearmanrsquos correlation between cardiac troponin T (cTnT)concentrations and echocardiographic parameters

Variables 119903119904

119875 Variables 119903119904119875

LVEDVi 010 044 IVCe (cm) 0209 007LVMi 018 014

Systolic function Diastolic functionLVEF () minus023 004lowast Average 1198641198901015840 005 066GLS () 044 lt0001lowast 119890

1015840 (cms) minus014 020LSRs (secminus1) 028 001lowast 119864 (ms) minus008 046CS () 023 0049lowast 119860 (ms) minus009 044CSRs (secminus1) 028 002lowast 119864119860 minus001 0951199041015840 (cms) minus010 039 LAVi 014 031lowast

119875 lt 005Abbreviations CS average circumferential strain CSRs circumferentialsystolic strain rate cTnT cardiac troponin T EDVi end-diastolic volumeindex EF ejection fraction 1198641198901015840 early transmitral velocity to tissue Dopplermitral annular early diastolic velocity ratio GLS global left ventricularpeak systolic longitudinal strain IVCe end-expiratory inferior vena cavadiameter LAVi left atrial volume index LSRs longitudinal systolic strainrate LV left ventricular LVMi left ventricular mass index SRs systolicstrain rate 1199041015840 left ventricular systolic myocardial velocity

(Table 4 full model) We subsequently performed a multi-variate Cox regression analysis with backward eliminationIn the final model (Table 4 reduced model 2) cTnT times 100a GLS ge minus15 and serum albumin were significant pre-dictors of mortality whereas background hypertension wasa marginally significant predictor There was no significantinteraction between cTnTtimes 100 and aGLSge minus15 in the finalmodelThe 95CIs of each HR in the Cox regressionmodelsshown in Table 4 are listed in Table S3

The additional predictive value of cTnT and GLS for all-cause mortality was investigated using a multivariate Coxregression with an analysis of deviance between differentmodels and an ROC curve analysis (Table 5) Using thesetwo analysis methods mortality was best predicted when thecTnT concentration and a GLS ge minus15 were simultaneouslyincluded in themodel incorporating the basic clinical param-eters In addition including either the cTnT concentration ora GLS ge minus15 in the model incorporating the basic clinicalparameters also increased the predictive power of the model

4 Discussion

The principal findings of the current study were that both thecTnT concentration and a GLS ge minus15 were independentand significant predictors of all-cause mortality despite themodest correlation between cTnT and GLS and added incre-mental predictive value in determining the risk of mortalitybeyond basic clinical parameters (background CAD diabetesand hypertension and serum albumin concentrations) instable hemodialysis patients with preserved LVEF The prog-nostic predictive value of the cTnT concentration could notbe replaced by GLS and vice versa

41 Relationship between cTnT Concentration and BaselineEchocardiographic Parameters and Clinical Characteristics

Despite contradictory findings [2] elevated cTnT concen-trations have been linked to LVH LV dilation and systolicand diastolic dysfunction in hemodialysis patients withoutcardiovascular symptoms [20 21 29ndash31] In the present studythe cTnT concentration was not significantly correlated withdiastolic functional parameters or LVMi possibly because thediastolic dysfunction and LVH were present in the majorityof the enrolled patients This finding of lacking a significantassociation between the cTnT concentration and LVMi issimilar to the study by DeFilippi et al [2] that also hadhigh prevalence of LVH in their enrolled patients The mostnoteworthy finding was that subtle LV systolic dysfunctionespecially represented as the GLS was modestly correlatedwith cTnT concentrationsThe cTnT concentration has also asignificant but weak associationwith other systolic functionalparameters including LVEF LSRs CS and CSRs (Table 3)This finding indicates that the elevated cTnT concentrationmay at least in part reflect subtle LV dysfunction but notLV diastolic dysfunction or mass in this patient populationwith high prevalence of LVH and diastolic dysfunction Onepossible explanation for this result is that some patients withsubtle LV dysfunction detected by measuring the GLS butnot other systolic parameters have concomitant subclinicalmyocyte injury andor stress resulting in the increase ofcTnT Furthermore myocardial stunning may contribute tothe subsequent development of systolic dysfunction in fixedsegment(s) even without reduction of LVEF in hemodialysispatients [32 33] resulting in a less negative GLS In additionit has been demonstrated that a high cTnT concentration isindependently associated with the presence or new develop-ment ofmyocardial stunning [34]This information indicatesthat elevated cTnT concentration and less negative GLSpossibly share some common underlying mechanisms

There was no significant difference in the prevalence ofCAD across tertiles of cTnT concentrations in the currentstudy Some studies [2 35 36] have suggested an associationbetween cTnT andCADbut others have failed to demonstrateany correlation [29 30 37] implying that CAD is not thesole causal factor for the increased cTnT concentrationsHowever we did find that dialysis patients with diabetes hadsignificantly elevated serum cTnT concentrations Severalstudies have indicated that diabetes is associated with raisedcTnT concentrations because of the presence of cardiacmicrovascular disease [29 38ndash40] in contrast Ooi andHouse [41] suggested that this association may result fromprotein glycosylation alteration of the degradation of themolecules andor reexpression of fetal genes

42 Association of Outcomes and Prognostic Predictive ValuesElevated cTnT concentration is a powerful prognostic predic-tor in the ESRD population [19 42ndash47] Several studies havereported associations between elevated cTnT concentrationand LVMi and LV dysfunction [2 19 20 31 48] however ele-vated cTnT concentration remains associated with mortalityafter adjustment for LVMi in hemodialysis patients [20] andafter adjustment for LVMi and LVEF in peritoneal dialysispatients [19] indicating that the prognostic value of cTnTreflects more than just LV mass and function In the present


Table4Cox

regressio

nanalysisfora

ll-causem

ortality

Basic

mod

elBa

sicmod

el+

cTnTtimes100

Basic

mod

el+

GLSgeminus15

Fullmod

elFu

llmod

el+

interactionterm

Redu

cedmod

el1

Redu

cedmod

el2

(finalm

odel)

Finalm

odel+

interactionterm

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR

119875

Album

in017

000

4lowast022

010

016

0003lowast

023

0047lowast

028

009

022

004lowast

024

004

8lowast029

009

CAD

262

004lowast

243

004lowast

196

016

212

012

222

011

221

010

mdashmdash

mdashmdash

DM

317

003lowast

210

035

297

004lowast

172

040

149

050

mdashmdash

mdashmdash

mdashmdash

HTN

339

002lowast

294

005lowast

309

002lowast

309

003lowast

264

009

300

004lowast

270

006

231

012

cTnTtimes100

mdashmdash

116

0001lowast

mdashmdash

113

000

9lowast119

001lowast

115

0001lowast

114

0002lowast

121

0001lowast

GLSgeminus15

mdashmdash

mdashmdash

357

002lowast

309

003lowast

400

007

337

002lowast

279

0049lowast

645

001lowast

(cTn

Ttimes100)

(GLSgeminus15)

mdashmdash

mdashmdash

mdashmdash

mdashmdash

091

022

mdashmdash

mdashmdash

090

014

Datapresentedarebasedon

theCox

regressio

nanalysis

95

CIsfor

each

HRarep

resented

inSupp

lementary

TableS

3In

multiv

ariateanalysis

wefi

rstly

constructedthemod

elinclu

ding

backgrou

ndcoronary

arteria

ldise

ase(C

AD)a

nddiabetes

andhypertensio

ntogether

with

serum

albu

min

concentrationas

abasic

mod

elthen

weaddedcTnTtimes100andor

aGLSgeminus15

into

thebasic

mod

elto

study

theire

ffects

onmortalityNextabackwardste

pwise

procedurewas

used

tochoo

sethefin

alredu

cedmod

elwith

varia

bles

significantat119875lt010beingretained

inthemod

elTo

obtain

anadequateredu

cedmod

elbefore

drop

ping

acovariatefro

mthem

odel

wec

onfirmed

thatits

absenced

idno

tresultinas

ubstantia

lchangeintheo

verallpredictin

gpo

wer

ofthem

odel

lowast

119875lt005(cTn

Ttimes100)

(GLSgeminus15)interactionbetweencTnTtimes100andGLSgeminus15

Abbreviatio

nsC

ADcoron

aryarteria

ldise

asecTnT

cardiac

tropo

ninTDMdiabetesGLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in(a

lessnegativ

eGLS

was

defin

edby

aGLSgeminus15)


Table5Ad

ditio

nalpredictivev

alueso

fcTn

Ttimes100andles

snegativeG

LS(geminus15)form

ortalityusingCox

regressio

nmod

elsa

nalysis

andRO

Ccurvea

nalysis

Thea

ddition

alvalueo

fcTn

Ttimes100andles

snegativeG

LS(geminus15)inmod

elpredictio

nform

ortalityusingCox

regressio

nmod

elsanalysiswith

analysis

ofdeviance

Thea

ddition

alpredictiv

evalue

ofcTnTtimes100andles

snegativeG

LS(geminus15)b

ased

onRO

Ccurvea

nalysis

with

calculated

AUCs

Chi-s

quare119875

AUC

95CI

119875

119875

Album

in+hypertensio

n+GLSgeminus15versus

albu

min

+hypertensio

n+GLSgeminus15+cTnTtimes100

988

0002lowast

Album

in+hypertensio

n068

(053

ndash081)

mdashmdash

Album

in+hypertensio

n+cTnTtimes100versus

albu

min

+hypertensio

n+cTnTtimes100+GLSgeminus15

456

005lowast

Album

in+hypertensio

n+GLSgeminus15

077

(065ndash088)

003lowast

mdash

Album

in+hypertensio

n+cTnTtimes100

078

(06ndash0

89)

002lowast

mdashAlbum

in+hypertensio


085

(075ndash094)lt0001lowast

mdashBa

sicmod

elversus

basic

mod

el+GLSgeminus15

451

003lowast

Basic

mod

el074

(062ndash086)

mdashmdash

Basic

mod

elversus

basic

mod

el+cTnTtimes100

987

0003lowast

Basic

mod

el+GLSgeminus15

081

(069ndash

091)

mdash004lowast

Basic

mod

el+GLSgeminus15versus

basic

mod

el+GLSgeminus15+cTnTtimes100

690

000

9lowastBa

sicmod

el+cTnTtimes100

082

(071ndash091)

mdash003lowast

Basic

mod

el+cTnTtimes100versus

basic

mod

el+cTnTtimes100+GLSgeminus15

453

004

6lowastBa

sicmod


089

(077ndash095)

mdash0001lowast

Basic

mod

elversus

basic

mod


1140

0002lowast

Firstweinclu

dedbackgrou

ndhypertensio

nandplasmaalbu

min

concentrationbu

texcludeddiabetes

andcoronary

arteria

ldise

asebasedon

finalredu

cedmod

elof

Table4

andstu

died

theadditio

nalp

redictive

values


snegativeGLS

(geminus15)tomortalityTh

enw

einclu

deddiabetes

andcoronary

arteria

ldise

asein

additio

nto

hypertensio

nandserum

albu

min

concentrationto

constructthe

basic

mod

elbecausethey

arecommon

lyused

forr

iskstr

atificatio

nin

thehemod

ialysis

popu

latio

nandstu

died

theadditio

nalp

redictivevalues


snegativeGLS

(geminus15)tomortalitylowast

119875lt005

com

parin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndhypertensio

nandplasmaa

lbum

inconcentration

comparin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndcoronary

arteria

ldise

asediabetes

andhypertensio

nandplasmaa

lbum

inconcentration

Abbreviatio

nsA

UC

area

underc

urveC

Iconfi

denceintervalcTnT

cardiac

tropo

ninT

GLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in


study LVH and LVMiwere not significant predictors possiblybecause most of the enrolled patients had LVH It should benoted that most stable hemodialysis patients have LVH andpreserved LVEF [2 29] and our finding indicates that cTnTconcentrations and GLS are useful indicators in evaluatingthe prognosis in such a population

We found that cTnT concentrations and a GLS ge minus15but not LVEF or other systolic echocardiogram parameterswere independently associated with mortality Although GLSmodestly correlated with LVEF (Table S1) the LVEF reflectsLV radial and transverse function and only partially reflectslongitudinal function whereas GLS mainly reflects LV longi-tudinal function [17 49] LV longitudinal function is largelydetermined by the subendocardial region and GLS may thusbe more sensitive in detecting the presence of pathologicalconditions such as myocardial ischemia or fibrosis [17 4950] which might explain the predictive value of GLS forlong-term prognosis in hemodialysis patients with preservedLVEF The reasons for the differences in outcome predictionof cTnT and less negative GLS are unclear CTnT is a cardiacinjury marker whereas GLS is a functional marker and ourfindings suggest they may capture different or residual risksassociated with poor outcomes

The prognostic value of elevated cTnT concentrations andGLS ge minus15 might not be attributed to background diabetesor CAD as demonstrated by the finding that no substantialchange in the HRs of cTnT and a GLS ge minus15 was foundwhen cTnT and a less negative GLS were added to the modelregardless of whether themodel was adjusted for backgroundCAD and diabetes (full model and reduced models 1 and 2 inTable 4)

43 Possible Clinical Implications Given that cTnT concen-trations and a GLS ge minus15 have additional prognostic valuebeyond conventional echocardiographic and clinical param-eters echocardiography (with STE) should be performed inconjunction with measurement of cTnT concentrations forearly risk stratification in stable hemodialysis patients withpreserved LVEF

An STE study includes longitudinal radial and circum-ferential strains and twist measurements the thorough strainmeasurement is complicated and may be time-consumingespecially for inexperienced operators All STE-measuredparameters can be collected in research studies howeverthe measuring GLS is particularly useful because it appearsto be highly sensitive relevant for prognosis and morereproducible than either circumferential or radial strain inthe general population [51 52] and in stable hemodialysispatients with preserved LVEF To simplify the strain exami-nation in clinical practice assessment of only the longitudinalstrain may be used to facilitate the analysis With thiskind of modified STE analysis the measurement of GLSgenerally only requires 2ndash4 minutes and may be feasible asa component of routine echocardiographic examinations inclinical practice [53]

44 Study Limitations The current study has several limi-tations First the number of enrolled patients was limited

therefore this study may not have had sufficient powerto explore all of the factors associated with mortality Inaddition we were not able to analyze the impact of cTnTconcentrations and GLS ge minus15 on cause-specific mortalitysuch as cardiovascular mortality With the current samplesize however we already had sufficient statistical power todetect significant effects of cTnT concentrations and a GLSge minus15 on all-cause mortality and therefore the findingswere statistically significant Nevertheless a study with alarger sample size will enable the simultaneous evaluationof more predictors in the future and may help confirm ourfindings Second patients with low LVEF (lt50) andorHF were not enrolled in the current study which limits thegeneralizability of our findings to a general hemodialysis pop-ulation However the serum cTnT concentration [54ndash56] andGLS [57ndash59] were predictive of the prognosis in nondialysisacute and chronic HF patients with varying LVEF valuesWhether the measurement of cTnT concentrations or GLS orthe combination thereof is also useful for risk stratificationin a general hemodialysis population including patients withlow LVEF andor HF warrants further studies Third somedialysis patients had severe valvular heart diseases atrialfibrillation or poor echocardiographic image quality whichexcluded the possibility of GLS analysis Finally we didnot measure brain natriuretic peptide concentrations in thisstudy

45 Conclusions Both the cTnT concentration and a GLSge minus15 are powerful independent predictors of all-causemortality and add prognostic value to the clinical andconventional echocardiographic parameters in current usethus enabling the early identification of high-risk patients andinform clinical decision making among stable hemodialysispatients with preserved LVEF Further studies are warrantedto define effective and early intervention strategies for thesehigh-risk patients

Conflict of Interests

The authors declare that they have no conflict of interests

Authorsrsquo Contribution

Yen-Wen Liu Chi-Ting Su Wei-Chuan Tsai Liang-MiinTsai Jyh-Hong Chen and Junne-Ming Sung designed thestudy Yen-WenLiu performed and analyzed echocardiogramstudies Yen-Wen Liu Chi-Ting Su Yu-Tzu Chang SaprinaPHWang Chun-Shin Yang and Junne-Ming Sung collectedthe patientsrsquo data Yen-WenLiu Yu-Ru Su Yu-TzuChang andJunne-Ming Sung performed the statistical analyses andYen-Wen Liu and Junne-Ming Sung wrote the paper

Acknowledgments

This study was partially supported by the National ScienceCouncil (NSC) Executive Yuan Taipei Taiwan Grants NSC101-2314-B-006-035 and 102-2314-B-006-014 for JM Sung


The funders had no role in study design data collection andanalysis decision to publish or preparation of the paper

References

[1] C P Wen T Y D Cheng M K Tsai et al ldquoAll-cause mortalityattributable to chronic kidney disease a prospective cohortstudy based on 462 293 adults in Taiwanrdquo The Lancet vol 371no 9631 pp 2173ndash2182 2008

[2] C DeFilippi SWasserman S Rosanio et al ldquoCardiac troponinT and C-reactive protein for predicting prognosis coronaryatherosclerosis and cardiomyopathy in patients undergoinglong-term hemodialysisrdquo Journal of the American MedicalAssociation vol 290 no 3 pp 353ndash359 2003

[3] W-C Yang and S-J Hwang ldquoIncidence prevalence and mor-tality trends of dialysis end-stage renal disease in Taiwanfrom 1990 to 2001 the impact of national health insurancerdquoNephrology Dialysis Transplantation vol 23 no 12 pp 3977ndash3982 2008

[4] P S Parfrey R N Foley J D Harnett G M Kent D CMurray and P E Barre ldquoOutcome and risk factors for leftventricular disorders in chronic uraemiardquo Nephrology DialysisTransplantation vol 11 no 7 pp 1277ndash1285 1996

[5] C Zoccali F A Benedetto F Mallamaci et al ldquoPrognosticvalue of echocardiographic indicators of left ventricular systolicfunction in asymptomatic dialysis patientsrdquo Journal of theAmerican Society of Nephrology vol 15 no 4 pp 1029ndash10372004

[6] A Y-M Wang M Wang C W-K Lam I H-S Chan S-FLui and J E Sanderson ldquoHeart failure in long-term peritonealdialysis patients a 4-Year prospective analysisrdquo Clinical Journalof the American Society of Nephrology vol 6 no 4 pp 805ndash8122011

[7] ldquoKDOQI clinical practice guidelines for cardiovascular diseasein dialysis patientsrdquo American Journal of Kidney vol 45 no 3pp S1ndashS153 2005

[8] J D Harnett R N Foley G M Kent P E Barre D Murrayand P S Parfrey ldquoCongestive heart failure in dialysis patientsprevalence incidence prognosis and risk factorsrdquo Kidney Inter-national vol 47 no 3 pp 884ndash890 1995

[9] J M Soucie and W M McClellan ldquoEarly death in dialysispatients risk factors and impact on incidence and mortalityratesrdquo Journal of the American Society of Nephrology vol 7 no10 pp 2169ndash2175 1996

[10] A Y-M Wang and J E Sanderson ldquoTreatment of heart failurein long-term dialysis patients a reappraisalrdquo American Journalof Kidney Diseases vol 57 no 5 pp 760ndash772 2011

[11] C Zoccali F A Benedetto G Tripepi et al ldquoLeft ventricularsystolic function monitoring in asymptomatic dialysis patientsa prospective cohort studyrdquo Journal of the American Society ofNephrology vol 17 no 5 pp 1460ndash1465 2006

[12] A Y Wang M Wang C W Lam I H Chan S F Lui and JE Sanderson ldquoHeart failure with preserved or reduced ejectionfraction in patients treated with peritoneal dialysisrdquo AmericanJournal of Kidney Diseases vol 61 no 6 pp 975ndash983 2013

[13] J Gorcsan III and H Tanaka ldquoEchocardiographic assessmentof myocardial strainrdquo Journal of the American College of Cardi-ology vol 58 no 14 pp 1401ndash1413 2011

[14] J Wang D S Khoury Y Yue G Torre-Amione and S FNagueh ldquoPreserved left ventricular twist and circumferential

deformation but depressed longitudinal and radial deforma-tion in patients with diastolic heart failurerdquo European HeartJournal vol 29 no 10 pp 1283ndash1289 2008

[15] Y-W Liu W-C Tsai C-T Su C-C Lin and J-H ChenldquoEvidence of left ventricular systolic dysfunction detected byautomated function imaging in patients with heart failure andpreserved left ventricular ejection fractionrdquo Journal of CardiacFailure vol 15 no 9 pp 782ndash789 2009

[16] Y-W Liu C-T Su Y-Y Huang et al ldquoLeft ventricular systolicstrain in chronic kidney disease and hemodialysis patientsrdquoAmerican Journal of Nephrology vol 33 no 1 pp 84ndash90 2011

[17] T Stanton R Leano andTHMarwick ldquoPrediction of all-causemortality from global longitudinal speckle strain comparisonwith ejection fraction and wall motion scoringrdquo CirculationCardiovascular Imaging vol 2 no 5 pp 356ndash364 2009

[18] Y W Liu C T Su J M Sung et al ldquoAssociation of leftventricular longitudinal strain with mortality among stablehemodialysis patients with preserved left ventricular ejectionfractionrdquoClinical Journal of the American Society of Nephrologyvol 8 pp 1564ndash1574 2013

[19] A Y-MWang CW-K LamMWang et al ldquoPrognostic valueof cardiac troponin T is independent of inflammation residualrenal function and cardiac hypertrophy and dysfunction inperitoneal dialysis patientsrdquo Clinical Chemistry vol 53 no 5pp 882ndash889 2007

[20] F Mallamaci C Zoccali S Parlongo et al ldquoTroponin isrelated to left ventricular mass and predicts all-cause andcardiovascular mortality in hemodialysis patientsrdquo AmericanJournal of Kidney Diseases vol 40 no 1 pp 68ndash75 2002

[21] M C Iliou C Fumeron M O Benoit et al ldquoFactors associatedwith increased serum levels of cardiac troponins T and I inchronic haemodialysis patients chronic Haemodialysis andnew Cardiac Markers Evaluation (CHANCE) studyrdquo Nephrol-ogy Dialysis Transplantation vol 16 no 7 pp 1452ndash1458 2001

[22] RM LangM Bierig R B Devereux et al ldquoRecommendationsfor chamber quantification a report from the American Societyof Echocardiographyrsquos guidelines and standards committee andthe Chamber Quantification Writing Group developed in con-junction with the European Association of Echocardiographya branch of the European Society of Cardiologyrdquo Journal of theAmerican Society of Echocardiography vol 18 no 12 pp 1440ndash1463 2005

[23] J J McMurray S Adamopoulos S D Anker et al ldquoESCGuidelines for the diagnosis and treatment of acute and chronicheart failure 2012 the Task Force for the Diagnosis andTreatment of Acute and Chronic Heart Failure 2012 of theEuropean Society of Cardiology Developed in collaborationwith theHeart Failure Association (HFA) of the ESCrdquo EuropeanHeart Journal vol 33 no 14 pp 1787ndash1847 2012

[24] S F Nagueh C P Appleton T C Gillebert et al ldquoCom-mendations for the evaluation of left ventricular diastolicfunction by echocardiographyrdquo Journal of the American Societyof Echocardiography vol 22 no 2 pp 107ndash133 2009

[25] Y Ando S Yanagiba and Y Asano ldquoThe inferior vena cavadiameter as a marker of dry weight in chronic hemodialyzedpatientsrdquo Artificial Organs vol 19 no 12 pp 1237ndash1242 1995

[26] National Kidney Foundation ldquoKDOQI clinical practice guide-lines and clinical practice recommendations for 2006 updateshemodialysis adequacy peritoneal dialysis adequacy and vas-cular accessrdquo American Journal of Kidney Diseases vol 48supplement 2 pp S1ndashS105 2006


[27] M Yashiro T Kamata N Yamadori M Tomita and EMuso ldquoEvaluation of markers to estimate volume status inhemodialysis patients atrial natriuretic peptide inferior venacava diameter blood volume changes and filtration coefficientsof microvasculaturerdquoTherapeutic Apheresis and Dialysis vol 11no 2 pp 131ndash137 2007

[28] T Yingchoncharoen S Agarwal Z B Popovic and H Mar-wick ldquoNormal ranges of left ventricular strain a meta-analysisrdquoJournal of the American Society of Echocardiography vol 26 no2 pp 185ndash191 2013

[29] R Sharma D C Gaze D Pellerin et al ldquoCardiac structural andfunctional abnormalities in end stage renal disease patients withelevated cardiac troponin Trdquo Heart vol 92 no 6 pp 804ndash8092006

[30] C R deFilippi EMThornM Aggarwal et al ldquoFrequency andcause of cardiac troponin T elevation in chronic hemodialysispatients from study of cardiovascular magnetic resonancerdquoAmerican Journal of Cardiology vol 100 no 5 pp 885ndash8892007

[31] F Mallamaci C Zoccali S Parlongo et al ldquoDiagnostic value oftroponin T for alterations in left ventricular mass and functionin dialysis patientsrdquo Kidney International vol 62 no 5 pp1884ndash1890 2002

[32] J O Burton H J Jefferies N M Selby and C W McIntyreldquoHemodialysis-induced cardiac injury determinants and asso-ciated outcomesrdquo Clinical Journal of the American Society ofNephrology vol 4 no 5 pp 914ndash920 2009

[33] J O Burton H J Jefferies N M Selby and C W McIntyreldquoHemodialysis-induced repetitive myocardial injury results inglobal and segmental reduction in systolic cardiac functionrdquoClinical Journal of the American Society of Nephrology vol 4no 12 pp 1925ndash1931 2009

[34] T Breidthardt J O Burton A Odudu M T Eldehni HJ Jefferies and C W McIntyre ldquoTroponin T for the detec-tion of dialysis-induced myocardial stunning in hemodialysispatientsrdquoClinical Journal of the American Society of Nephrologyvol 7 no 8 pp 1285ndash1292 2012

[35] C I Obialo S Sharda S Goyal E O Ofili A Oduwoleand N Gray ldquoAbility of troponin T to predict angiographiccoronary artery disease in patients with chronic kidney diseaserdquoAmerican Journal of Cardiology vol 94 no 6 pp 834ndash8362004

[36] THayashi YObi T Kimura et al ldquoCardiac troponinT predictsoccult coronary artery stenosis in patients with chronic kidneydisease at the start of renal replacement therapyrdquo NephrologyDialysis Transplantation vol 23 no 9 pp 2936ndash2942 2008

[37] Y-W Liu C-T Su S P H Wang et al ldquoApplication of speckle-tracking echocardiography in detecting coronary artery diseasein patients with maintenance hemodialysisrdquo Blood Purificationvol 32 no 1 pp 38ndash42 2011

[38] D S Ooi P A Isotalo and J P Veinot ldquoCorrelation of ante-mortem serum creatine kinase creatine kinase-MB troponin Iand troponin T with cardiac pathologyrdquoClinical Chemistry vol46 no 3 pp 338ndash344 2000

[39] D S Ooi D Zimmerman J Graham and G A Wells ldquoCar-diac troponin T predicts long-term outcomes in hemodialysispatientsrdquo Clinical Chemistry vol 47 no 3 pp 412ndash417 2001

[40] D-S Jeon M-Y Lee C-J Kim et al ldquoClinical findings inpatients with cardiac troponin T elevation and end-stage renaldisease without acute coronary syndromerdquoAmerican Journal ofCardiology vol 94 no 6 pp 831ndash834 2004

[41] D S Ooi and A A House ldquoCardiac troponin T in hemodia-lyzed patientsrdquo Clinical Chemistry vol 44 no 7 pp 1410ndash14161998

[42] J Dierkes U Domrose S Westphal et al ldquoCardiac troponin Tpredicts mortality in patients end-stage renal diseaserdquo Circula-tion vol 102 no 16 pp 1964ndash1969 2000

[43] P B Deegan M E Lafferty A Blumsohn I S Henderson andE McGregor ldquoPrognostic value of troponin T in hemodialysispatients is independent of comorbidityrdquo Kidney Internationalvol 60 no 6 pp 2399ndash2405 2001

[44] F S Apple M M Murakami L A Pearce and C A HerzogldquoPredictive value of cardiac troponin I and T for subsequentdeath in end-stage renal diseaserdquo Circulation vol 106 no 23pp 2941ndash2945 2002

[45] S Satyan R P Light and R Agarwal ldquoRelationships of N-terminal pro-Bnatriuretic peptide and cardiac troponin T to leftventricular mass and function and mortality in asymptomatichemodialysis patientsrdquo American Journal of Kidney Diseasesvol 50 no 6 pp 1009ndash1019 2007

[46] B Conway M McLaughlin P Sharpe and J Harty ldquoUse ofcardiac troponin T in diagnosis and prognosis of cardiac eventsin patients on chronic haemodialysisrdquo Nephrology DialysisTransplantation vol 20 no 12 pp 2759ndash2764 2005

[47] N A Khan B R Hemmelgarn M Tonelli C R Thompsonand A Levin ldquoPrognostic value of troponin T and I amongasymptomatic patients with end-stage renal disease a meta-analysisrdquo Circulation vol 112 no 20 pp 3088ndash3096 2005

[48] C Lowbeer S A Gustafsson A Seeberger F Bouvier and JHulting ldquoSerum cardiac troponin T in patients hospitalizedwith heart failure is associated with left ventricular hypertrophyand systolic dysfunctionrdquo Scandinavian Journal of Clinical andLaboratory Investigation vol 64 no 7 pp 667ndash676 2004

[49] H Geyer G Caracciolo H Abe et al ldquoAssessment of myocar-dial mechanics using speckle tracking echocardiography fun-damentals and clinical applicationsrdquo Journal of the AmericanSociety of Echocardiography vol 23 no 4 pp 351ndash369 2010

[50] J Brown C Jenkins and T H Marwick ldquoUse of myocardialstrain to assess global left ventricular function a comparisonwith cardiac magnetic resonance and 3-dimensional echocar-diographyrdquo American Heart Journal vol 157 no 1 pp 102ndashe12009

[51] M L Antoni S A Mollema V Delgado et al ldquoPrognosticimportance of strain and strain rate after acute myocardialinfarctionrdquo European Heart Journal vol 31 no 13 pp 1640ndash1647 2010

[52] V Mor-Avi R M Lang L P Badano et al ldquoCurrent and evolv-ing echocardiographic techniques for the quantitative eval-uation of cardiac mechanics ASEEAE consensus statementon methodology and indications endorsed by the JapaneseSociety of Echocardiographyrdquo Journal of the American Societyof Echocardiography vol 24 no 3 pp 277ndash313 2011

[53] H Feigenbaum R Mastouri and S Sawada ldquoA practicalapproach to using strain echocardiography to evaluate the leftventriclerdquoCirculation Journal vol 76 no 7 pp 1550ndash1555 2012

[54] M P Hudson CM OrsquoConnorW A Gattis et al ldquoImplicationsof elevated cardiac troponin t in ambulatory patients with heartfailure a prospective analysisrdquoAmerican Heart Journal vol 147no 3 pp 546ndash552 2004

[55] E R Perna S M Macın J P C Canella et al ldquoMinor myocar-dial damage detected by troponin T is a powerful predictorof long-term prognosis in patients with acute decompensated


heart failurerdquo International Journal of Cardiology vol 99 no 2pp 253ndash261 2005

[56] J S Healey R F Davies S J Smith R A Davies and D S OoildquoPrognostic use of cardiac troponin T and troponin I in patientswith heart failurerdquo Canadian Journal of Cardiology vol 19 no4 pp 383ndash386 2003

[57] AMignot E Donal A Zaroui et al ldquoGlobal longitudinal strainas amajor predictor of cardiac events in patients with depressedleft ventricular function a multicenter studyrdquo Journal of theAmerican Society of Echocardiography vol 23 no 10 pp 1019ndash1024 2010

[58] J Nahum A Bensaid C Dussault et al ldquoImpact of longitudinalmyocardial deformation on the prognosis of chronic heartfailure patientsrdquo Circulation Cardiovascular Imaging vol 3 no3 pp 249ndash256 2010

[59] M Iacoviello A Puzzovivo P Guida et al ldquoIndependentrole of left ventricular global longitudinal strain in predictingprognosis of chronic heart failure patientsrdquo Echocardiographyvol 30 no 7 pp 803ndash811 2013

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


For early detection of subclinical heart disease two-dimensional speckle-tracking echocardiography (STE) withmyocardial deformation (2D strain) analysis and themeasur-ing of serum cardiac biomarkers such as cardiac troponinT (cTnT) may be useful tools STE with 2D strain analysisis a quantitative method for the assessment of subtle LVdysfunction which cannot be evaluated by semiquantita-tive conventional echocardiography [11ndash16] Using 2D strainanalysis LV global peak systolic longitudinal strain (GLS)or circumferential strain (CS) is the ratio of the maximalchange in myocardial longitudinal or circumferential lengthin systole to the original length respectively During systolethe LV myocardium shortens in either direction thereforeGLS or CS has a negative value and less negative GLS orCS value indicates poorer global LV systolic function [13 16]GLS has been demonstrated to be a more sensitive predictorfor all-cause mortality than LVEF in the general population[17] We recently reported that a less negative GLS (definedas GLS ge minus15 ie an absolute value of GLS le 15) butnot LVEF predicted all-cause and cardiac mortality amongstable hemodialysis patients with preserved LVEF (LVEF ge50) indicating that GLS is a promising marker for earlyrisk stratification [18] As for serum cardiac biomarker highcirculating cTnT concentrations are associated with highmortality in dialysis patients [2 19 20] The food and drugadministration and the KDOQI guidelines [7] both indicatethe use of cTnT as a biomarker formortality risk stratificationin dialysis patients In our previous study we also foundthat the elevated cTnT concentration correlated with GLSand is associated with high mortality in this hemodialysispopulation [18]

Validation of a novel marker for risk stratification in aspecific population requires a phased approach Early-phasestudies should demonstrate that the novel marker is associ-ated with the outcome Midphase studies should explore therelationships between various markers and demonstrate thatthe new marker provides additional value beyond traditionaland other markers in identifying high-risk patients andorchanging the decision-making process The relationshipbetween cTnT concentrations and conventional echocardio-graphic parameters has been extensively studied in a generaldialysis population [2 19ndash21] however the relationshipbetween cTnT concentrations and subtle LV dysfunction andclinical characteristics in stable hemodialysis patients withpreserved LVEF is still unclear though we have noted thatthe cTnT concentration correlated with GLS in our previousstudy [18] Furthermore because cTnT might correlate withGLS it raises a question of whether the association of cTnTwith mortality remains significant after adjustment for otherprognostic factors including GLS In other words whethercTnT can replace GLS in risk stratification or vice versais still unknown In addition it remains unclear whetherthere is an additional prognostic value of cTnT or a GLSge minus15 or their combination beyond other prognosticfactors In this study we explored the relationships betweencTnT concentrations and patientsrsquo characteristics and STE-measured echocardiographic parameters and evaluated theadditional prognostic value provided by cTnT or a GLS geminus15 or their interaction to define their clinical usefulness

2 Subjects and Methods

21 Patients This study adhered to the Declaration ofHelsinki and all enrolled patients provided written informedconsent The study protocol was approved by the HumanResearch andEthicsCommittee of our institute (IRBnumberER-98-073) As previously described [18] from December2008 to January 2009 adult stable hemodialysis patients (ge18years old) receiving a maintenance hemodialysis programconsisting of 4 hours a session thrice weekly for more than3 months were prospectively enrolled from two communityhospitals in Yun-Lin County Taiwan National Cheng KungUniversity Hospital Dou-Liou Branch and Catholic Fu-AnHospital In total 120 hemodialysis patients without intercur-rent or terminal illnesses were screened and 109 patients wereincluded (3 with starting long-term hemodialysis lt3 monthsand 8 without the willingness to participate) Additionalpatients were subsequently excluded because of old age (ge80years 119899 = 3) LVEF lt50 (119899 = 2) or episodic or persistentHF (geNYHA FC III) [22 23] within 6 months (119899 = 3)Patients with chronic atrial fibrillation (119899 = 4) recentinfarction (119899 = 1) severe valvular heart disease (119899 = 2) orinadequate image quality (119899 = 6) were also excluded The 88enrolled patients were followed for 31 months or until deathUpon enrollment and during the follow-up period clinicalinformation on comorbidities medical history and cardio-vascularmedicationwere obtained by a careful review of eachpatientrsquos medical record andor a self-reported questionnaireThe primary outcome was all-cause mortality

22 Biochemical Measurements Blood was collected beforethe midweek dialysis session in the same week that theechocardiographic study was performed Sera were stored atminus80∘C until analysis when they were thawed for measure-ment of the concentrations of cTnT (4th generation TroponinT STAT immunoassay ElecSys 2010 System Roche Diag-nostics Indianapolis IN USA) high-sensitivity C-reactiveprotein (BN II analyzer Dade Behring Glasgow DE USA)interleukin-6 (chemiluminescent sandwich ELISA Quan-tikine Human interleukin-6 RampD Systems Inc Minneapo-lis MN USA) and procollagen type I C-terminal peptide(Takara Bio Inc Otsu Shiga Japan) The measurements ofcTnT concentrationwere performed in the clinical laboratoryat National Cheng-Kung University Hospital and were super-vised by one of the coauthors (YWL) CTnT concentrationswere assayed in batch using the automated ElecSys 2010analyzer The lower limit of detection for this assay is001 ngmL which also reflects the 99th percentile cutoff limitfor detection of myocardial necrosis In our laboratory thecoefficient of variation (CV) at 0078 ngmL is 50 and theCV at 2300 ngmL is 25 Serum cholesterol triglyceridescalcium phosphate and albumin were measured using anautomatic analyzer

23 Echocardiographic Measurements All patients wereexamined by one well-trained cardiologist (YWL with 10years of experience in echocardiographic examination) usingan ultrasound system with a 35MHz probe (Vivid-i GE




(cTnT le 002 ngmL119899 = 30)


119899 = 29)








1015840




10

08

06

04

02

00

0 10 20 30 40


High cTnT group

Cum

surv

ival


Log rank P = 0003

(a)

06

04

02

00

0 10 20 30 40


cTnT gt 0042ngmL

cTnT le 0042ngmLCum

haz

ard

uarr 285X

P = 0001

cTnT gt 0042

cTnT le 0042ngmL

(b)





3 Results





(cTnT le 002 ngmL 119899 = 30)


119899 = 29)














119875 Variables 119903119904119875







4 Discussion







Table4Cox

regressio

nanalysisfora

ll-causem

ortality

Basic

mod

elBa

sicmod

el+

cTnTtimes100

Basic

mod

el+

GLSgeminus15

Fullmod

elFu

llmod

el+

interactionterm

Redu

cedmod

el1

Redu

cedmod

el2

(finalm

odel)

Finalm

odel+

interactionterm

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR

119875

Album

in017

000

4lowast022

010

016

0003lowast

023

0047lowast

028

009

022

004lowast

024

004

8lowast029

009

CAD

262

004lowast

243

004lowast

196

016

212

012

222

011

221

010

mdashmdash

mdashmdash

DM

317

003lowast

210

035

297

004lowast

172

040

149

050

mdashmdash

mdashmdash

mdashmdash

HTN

339

002lowast

294

005lowast

309

002lowast

309

003lowast

264

009

300

004lowast

270

006

231

012

cTnTtimes100

mdashmdash

116

0001lowast

mdashmdash

113

000

9lowast119

001lowast

115

0001lowast

114

0002lowast

121

0001lowast

GLSgeminus15

mdashmdash

mdashmdash

357

002lowast

309

003lowast

400

007

337

002lowast

279

0049lowast

645

001lowast

(cTn

Ttimes100)

(GLSgeminus15)

mdashmdash

mdashmdash

mdashmdash

mdashmdash

091

022

mdashmdash

mdashmdash

090

014


theCox

regressio

nanalysis

95

CIsfor

each

HRarep

resented

inSupp

lementary

TableS

3In

multiv

ariateanalysis

wefi

rstly

constructedthemod

elinclu

ding

backgrou

ndcoronary

arteria

ldise

ase(C

AD)a

nddiabetes

andhypertensio

ntogether

with

serum

albu

min

concentrationas

abasic

mod

elthen


aGLSgeminus15

into

thebasic

mod

elto

study

theire

ffects


pwise

procedurewas

used

tochoo

sethefin

alredu

cedmod

elwith

varia

bles


inthemod

elTo

obtain

anadequateredu

cedmod

elbefore

drop

ping

acovariatefro

mthem

odel

wec

onfirmed

thatits

absenced

idno

tresultinas

ubstantia

lchangeintheo

verallpredictin

gpo

wer

ofthem

odel

lowast

119875lt005(cTn

Ttimes100)


Abbreviatio

nsC

ADcoron

aryarteria

ldise

asecTnT

cardiac

tropo

ninTDMdiabetesGLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in(a

lessnegativ

eGLS

was

defin

edby

aGLSgeminus15)


Table5Ad

ditio

nalpredictivev

alueso

fcTn

Ttimes100andles

snegativeG

LS(geminus15)form

ortalityusingCox

regressio

nmod

elsa

nalysis

andRO

Ccurvea

nalysis

Thea

ddition

alvalueo

fcTn

Ttimes100andles

snegativeG

LS(geminus15)inmod

elpredictio

nform

ortalityusingCox

regressio

nmod

elsanalysiswith

analysis

ofdeviance

Thea

ddition

alpredictiv

evalue


snegativeG

LS(geminus15)b

ased

onRO

Ccurvea

nalysis

with

calculated

AUCs

Chi-s

quare119875

AUC

95CI

119875

119875

Album

in+hypertensio


albu

min

+hypertensio


988

0002lowast

Album

in+hypertensio

n068

(053

ndash081)

mdashmdash

Album

in+hypertensio


albu

min

+hypertensio


456

005lowast

Album

in+hypertensio

n+GLSgeminus15

077

(065ndash088)

003lowast

mdash

Album

in+hypertensio

n+cTnTtimes100

078

(06ndash0

89)

002lowast

mdashAlbum

in+hypertensio


085


mdashBa

sicmod

elversus

basic

mod

el+GLSgeminus15

451

003lowast

Basic

mod

el074

(062ndash086)

mdashmdash

Basic

mod

elversus

basic

mod

el+cTnTtimes100

987

0003lowast

Basic

mod

el+GLSgeminus15

081

(069ndash

091)

mdash004lowast

Basic

mod


basic

mod


690

000

9lowastBa

sicmod

el+cTnTtimes100

082

(071ndash091)

mdash003lowast

Basic

mod


basic

mod


453

004

6lowastBa

sicmod


089

(077ndash095)

mdash0001lowast

Basic

mod

elversus

basic

mod


1140

0002lowast

Firstweinclu

dedbackgrou

ndhypertensio

nandplasmaalbu

min

concentrationbu

texcludeddiabetes

andcoronary

arteria

ldise

asebasedon

finalredu

cedmod

elof

Table4

andstu

died

theadditio

nalp

redictive

values


snegativeGLS


enw

einclu

deddiabetes

andcoronary

arteria

ldise

asein

additio

nto

hypertensio

nandserum

albu

min

concentrationto

constructthe

basic

mod

elbecausethey

arecommon

lyused

forr

iskstr

atificatio

nin

thehemod

ialysis

popu

latio

nandstu

died

theadditio

nalp

redictivevalues


snegativeGLS


119875lt005

com

parin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndhypertensio

nandplasmaa

lbum

inconcentration

comparin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndcoronary

arteria

ldise

asediabetes

andhypertensio

nandplasmaa

lbum

inconcentration

Abbreviatio

nsA

UC

area

underc

urveC

Iconfi

denceintervalcTnT

cardiac

tropo

ninT

GLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in














Acknowledgments




References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















(cTnT le 002 ngmL119899 = 30)


119899 = 29)








1015840




10

08

06

04

02

00

0 10 20 30 40


High cTnT group

Cum

surv

ival


Log rank P = 0003

(a)

06

04

02

00

0 10 20 30 40


cTnT gt 0042ngmL

cTnT le 0042ngmLCum

haz

ard

uarr 285X

P = 0001

cTnT gt 0042

cTnT le 0042ngmL

(b)





3 Results





(cTnT le 002 ngmL 119899 = 30)


119899 = 29)














119875 Variables 119903119904119875







4 Discussion







Table4Cox

regressio

nanalysisfora

ll-causem

ortality

Basic

mod

elBa

sicmod

el+

cTnTtimes100

Basic

mod

el+

GLSgeminus15

Fullmod

elFu

llmod

el+

interactionterm

Redu

cedmod

el1

Redu

cedmod

el2

(finalm

odel)

Finalm

odel+

interactionterm

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR

119875

Album

in017

000

4lowast022

010

016

0003lowast

023

0047lowast

028

009

022

004lowast

024

004

8lowast029

009

CAD

262

004lowast

243

004lowast

196

016

212

012

222

011

221

010

mdashmdash

mdashmdash

DM

317

003lowast

210

035

297

004lowast

172

040

149

050

mdashmdash

mdashmdash

mdashmdash

HTN

339

002lowast

294

005lowast

309

002lowast

309

003lowast

264

009

300

004lowast

270

006

231

012

cTnTtimes100

mdashmdash

116

0001lowast

mdashmdash

113

000

9lowast119

001lowast

115

0001lowast

114

0002lowast

121

0001lowast

GLSgeminus15

mdashmdash

mdashmdash

357

002lowast

309

003lowast

400

007

337

002lowast

279

0049lowast

645

001lowast

(cTn

Ttimes100)

(GLSgeminus15)

mdashmdash

mdashmdash

mdashmdash

mdashmdash

091

022

mdashmdash

mdashmdash

090

014


theCox

regressio

nanalysis

95

CIsfor

each

HRarep

resented

inSupp

lementary

TableS

3In

multiv

ariateanalysis

wefi

rstly

constructedthemod

elinclu

ding

backgrou

ndcoronary

arteria

ldise

ase(C

AD)a

nddiabetes

andhypertensio

ntogether

with

serum

albu

min

concentrationas

abasic

mod

elthen


aGLSgeminus15

into

thebasic

mod

elto

study

theire

ffects


pwise

procedurewas

used

tochoo

sethefin

alredu

cedmod

elwith

varia

bles


inthemod

elTo

obtain

anadequateredu

cedmod

elbefore

drop

ping

acovariatefro

mthem

odel

wec

onfirmed

thatits

absenced

idno

tresultinas

ubstantia

lchangeintheo

verallpredictin

gpo

wer

ofthem

odel

lowast

119875lt005(cTn

Ttimes100)


Abbreviatio

nsC

ADcoron

aryarteria

ldise

asecTnT

cardiac

tropo

ninTDMdiabetesGLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in(a

lessnegativ

eGLS

was

defin

edby

aGLSgeminus15)


Table5Ad

ditio

nalpredictivev

alueso

fcTn

Ttimes100andles

snegativeG

LS(geminus15)form

ortalityusingCox

regressio

nmod

elsa

nalysis

andRO

Ccurvea

nalysis

Thea

ddition

alvalueo

fcTn

Ttimes100andles

snegativeG

LS(geminus15)inmod

elpredictio

nform

ortalityusingCox

regressio

nmod

elsanalysiswith

analysis

ofdeviance

Thea

ddition

alpredictiv

evalue


snegativeG

LS(geminus15)b

ased

onRO

Ccurvea

nalysis

with

calculated

AUCs

Chi-s

quare119875

AUC

95CI

119875

119875

Album

in+hypertensio


albu

min

+hypertensio


988

0002lowast

Album

in+hypertensio

n068

(053

ndash081)

mdashmdash

Album

in+hypertensio


albu

min

+hypertensio


456

005lowast

Album

in+hypertensio

n+GLSgeminus15

077

(065ndash088)

003lowast

mdash

Album

in+hypertensio

n+cTnTtimes100

078

(06ndash0

89)

002lowast

mdashAlbum

in+hypertensio


085


mdashBa

sicmod

elversus

basic

mod

el+GLSgeminus15

451

003lowast

Basic

mod

el074

(062ndash086)

mdashmdash

Basic

mod

elversus

basic

mod

el+cTnTtimes100

987

0003lowast

Basic

mod

el+GLSgeminus15

081

(069ndash

091)

mdash004lowast

Basic

mod


basic

mod


690

000

9lowastBa

sicmod

el+cTnTtimes100

082

(071ndash091)

mdash003lowast

Basic

mod


basic

mod


453

004

6lowastBa

sicmod


089

(077ndash095)

mdash0001lowast

Basic

mod

elversus

basic

mod


1140

0002lowast

Firstweinclu

dedbackgrou

ndhypertensio

nandplasmaalbu

min

concentrationbu

texcludeddiabetes

andcoronary

arteria

ldise

asebasedon

finalredu

cedmod

elof

Table4

andstu

died

theadditio

nalp

redictive

values


snegativeGLS


enw

einclu

deddiabetes

andcoronary

arteria

ldise

asein

additio

nto

hypertensio

nandserum

albu

min

concentrationto

constructthe

basic

mod

elbecausethey

arecommon

lyused

forr

iskstr

atificatio

nin

thehemod

ialysis

popu

latio

nandstu

died

theadditio

nalp

redictivevalues


snegativeGLS


119875lt005

com

parin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndhypertensio

nandplasmaa

lbum

inconcentration

comparin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndcoronary

arteria

ldise

asediabetes

andhypertensio

nandplasmaa

lbum

inconcentration

Abbreviatio

nsA

UC

area

underc

urveC

Iconfi

denceintervalcTnT

cardiac

tropo

ninT

GLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in














Acknowledgments




References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















10

08

06

04

02

00

0 10 20 30 40


High cTnT group

Cum

surv

ival


Log rank P = 0003

(a)

06

04

02

00

0 10 20 30 40


cTnT gt 0042ngmL

cTnT le 0042ngmLCum

haz

ard

uarr 285X

P = 0001

cTnT gt 0042

cTnT le 0042ngmL

(b)





3 Results





(cTnT le 002 ngmL 119899 = 30)


119899 = 29)














119875 Variables 119903119904119875







4 Discussion







Table4Cox

regressio

nanalysisfora

ll-causem

ortality

Basic

mod

elBa

sicmod

el+

cTnTtimes100

Basic

mod

el+

GLSgeminus15

Fullmod

elFu

llmod

el+

interactionterm

Redu

cedmod

el1

Redu

cedmod

el2

(finalm

odel)

Finalm

odel+

interactionterm

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR

119875

Album

in017

000

4lowast022

010

016

0003lowast

023

0047lowast

028

009

022

004lowast

024

004

8lowast029

009

CAD

262

004lowast

243

004lowast

196

016

212

012

222

011

221

010

mdashmdash

mdashmdash

DM

317

003lowast

210

035

297

004lowast

172

040

149

050

mdashmdash

mdashmdash

mdashmdash

HTN

339

002lowast

294

005lowast

309

002lowast

309

003lowast

264

009

300

004lowast

270

006

231

012

cTnTtimes100

mdashmdash

116

0001lowast

mdashmdash

113

000

9lowast119

001lowast

115

0001lowast

114

0002lowast

121

0001lowast

GLSgeminus15

mdashmdash

mdashmdash

357

002lowast

309

003lowast

400

007

337

002lowast

279

0049lowast

645

001lowast

(cTn

Ttimes100)

(GLSgeminus15)

mdashmdash

mdashmdash

mdashmdash

mdashmdash

091

022

mdashmdash

mdashmdash

090

014


theCox

regressio

nanalysis

95

CIsfor

each

HRarep

resented

inSupp

lementary

TableS

3In

multiv

ariateanalysis

wefi

rstly

constructedthemod

elinclu

ding

backgrou

ndcoronary

arteria

ldise

ase(C

AD)a

nddiabetes

andhypertensio

ntogether

with

serum

albu

min

concentrationas

abasic

mod

elthen


aGLSgeminus15

into

thebasic

mod

elto

study

theire

ffects


pwise

procedurewas

used

tochoo

sethefin

alredu

cedmod

elwith

varia

bles


inthemod

elTo

obtain

anadequateredu

cedmod

elbefore

drop

ping

acovariatefro

mthem

odel

wec

onfirmed

thatits

absenced

idno

tresultinas

ubstantia

lchangeintheo

verallpredictin

gpo

wer

ofthem

odel

lowast

119875lt005(cTn

Ttimes100)


Abbreviatio

nsC

ADcoron

aryarteria

ldise

asecTnT

cardiac

tropo

ninTDMdiabetesGLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in(a

lessnegativ

eGLS

was

defin

edby

aGLSgeminus15)


Table5Ad

ditio

nalpredictivev

alueso

fcTn

Ttimes100andles

snegativeG

LS(geminus15)form

ortalityusingCox

regressio

nmod

elsa

nalysis

andRO

Ccurvea

nalysis

Thea

ddition

alvalueo

fcTn

Ttimes100andles

snegativeG

LS(geminus15)inmod

elpredictio

nform

ortalityusingCox

regressio

nmod

elsanalysiswith

analysis

ofdeviance

Thea

ddition

alpredictiv

evalue


snegativeG

LS(geminus15)b

ased

onRO

Ccurvea

nalysis

with

calculated

AUCs

Chi-s

quare119875

AUC

95CI

119875

119875

Album

in+hypertensio


albu

min

+hypertensio


988

0002lowast

Album

in+hypertensio

n068

(053

ndash081)

mdashmdash

Album

in+hypertensio


albu

min

+hypertensio


456

005lowast

Album

in+hypertensio

n+GLSgeminus15

077

(065ndash088)

003lowast

mdash

Album

in+hypertensio

n+cTnTtimes100

078

(06ndash0

89)

002lowast

mdashAlbum

in+hypertensio


085


mdashBa

sicmod

elversus

basic

mod

el+GLSgeminus15

451

003lowast

Basic

mod

el074

(062ndash086)

mdashmdash

Basic

mod

elversus

basic

mod

el+cTnTtimes100

987

0003lowast

Basic

mod

el+GLSgeminus15

081

(069ndash

091)

mdash004lowast

Basic

mod


basic

mod


690

000

9lowastBa

sicmod

el+cTnTtimes100

082

(071ndash091)

mdash003lowast

Basic

mod


basic

mod


453

004

6lowastBa

sicmod


089

(077ndash095)

mdash0001lowast

Basic

mod

elversus

basic

mod


1140

0002lowast

Firstweinclu

dedbackgrou

ndhypertensio

nandplasmaalbu

min

concentrationbu

texcludeddiabetes

andcoronary

arteria

ldise

asebasedon

finalredu

cedmod

elof

Table4

andstu

died

theadditio

nalp

redictive

values


snegativeGLS


enw

einclu

deddiabetes

andcoronary

arteria

ldise

asein

additio

nto

hypertensio

nandserum

albu

min

concentrationto

constructthe

basic

mod

elbecausethey

arecommon

lyused

forr

iskstr

atificatio

nin

thehemod

ialysis

popu

latio

nandstu

died

theadditio

nalp

redictivevalues


snegativeGLS


119875lt005

com

parin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndhypertensio

nandplasmaa

lbum

inconcentration

comparin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndcoronary

arteria

ldise

asediabetes

andhypertensio

nandplasmaa

lbum

inconcentration

Abbreviatio

nsA

UC

area

underc

urveC

Iconfi

denceintervalcTnT

cardiac

tropo

ninT

GLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in














Acknowledgments




References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















(cTnT le 002 ngmL 119899 = 30)


119899 = 29)














119875 Variables 119903119904119875







4 Discussion







Table4Cox

regressio

nanalysisfora

ll-causem

ortality

Basic

mod

elBa

sicmod

el+

cTnTtimes100

Basic

mod

el+

GLSgeminus15

Fullmod

elFu

llmod

el+

interactionterm

Redu

cedmod

el1

Redu

cedmod

el2

(finalm

odel)

Finalm

odel+

interactionterm

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR

119875

Album

in017

000

4lowast022

010

016

0003lowast

023

0047lowast

028

009

022

004lowast

024

004

8lowast029

009

CAD

262

004lowast

243

004lowast

196

016

212

012

222

011

221

010

mdashmdash

mdashmdash

DM

317

003lowast

210

035

297

004lowast

172

040

149

050

mdashmdash

mdashmdash

mdashmdash

HTN

339

002lowast

294

005lowast

309

002lowast

309

003lowast

264

009

300

004lowast

270

006

231

012

cTnTtimes100

mdashmdash

116

0001lowast

mdashmdash

113

000

9lowast119

001lowast

115

0001lowast

114

0002lowast

121

0001lowast

GLSgeminus15

mdashmdash

mdashmdash

357

002lowast

309

003lowast

400

007

337

002lowast

279

0049lowast

645

001lowast

(cTn

Ttimes100)

(GLSgeminus15)

mdashmdash

mdashmdash

mdashmdash

mdashmdash

091

022

mdashmdash

mdashmdash

090

014


theCox

regressio

nanalysis

95

CIsfor

each

HRarep

resented

inSupp

lementary

TableS

3In

multiv

ariateanalysis

wefi

rstly

constructedthemod

elinclu

ding

backgrou

ndcoronary

arteria

ldise

ase(C

AD)a

nddiabetes

andhypertensio

ntogether

with

serum

albu

min

concentrationas

abasic

mod

elthen


aGLSgeminus15

into

thebasic

mod

elto

study

theire

ffects


pwise

procedurewas

used

tochoo

sethefin

alredu

cedmod

elwith

varia

bles


inthemod

elTo

obtain

anadequateredu

cedmod

elbefore

drop

ping

acovariatefro

mthem

odel

wec

onfirmed

thatits

absenced

idno

tresultinas

ubstantia

lchangeintheo

verallpredictin

gpo

wer

ofthem

odel

lowast

119875lt005(cTn

Ttimes100)


Abbreviatio

nsC

ADcoron

aryarteria

ldise

asecTnT

cardiac

tropo

ninTDMdiabetesGLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in(a

lessnegativ

eGLS

was

defin

edby

aGLSgeminus15)


Table5Ad

ditio

nalpredictivev

alueso

fcTn

Ttimes100andles

snegativeG

LS(geminus15)form

ortalityusingCox

regressio

nmod

elsa

nalysis

andRO

Ccurvea

nalysis

Thea

ddition

alvalueo

fcTn

Ttimes100andles

snegativeG

LS(geminus15)inmod

elpredictio

nform

ortalityusingCox

regressio

nmod

elsanalysiswith

analysis

ofdeviance

Thea

ddition

alpredictiv

evalue


snegativeG

LS(geminus15)b

ased

onRO

Ccurvea

nalysis

with

calculated

AUCs

Chi-s

quare119875

AUC

95CI

119875

119875

Album

in+hypertensio


albu

min

+hypertensio


988

0002lowast

Album

in+hypertensio

n068

(053

ndash081)

mdashmdash

Album

in+hypertensio


albu

min

+hypertensio


456

005lowast

Album

in+hypertensio

n+GLSgeminus15

077

(065ndash088)

003lowast

mdash

Album

in+hypertensio

n+cTnTtimes100

078

(06ndash0

89)

002lowast

mdashAlbum

in+hypertensio


085


mdashBa

sicmod

elversus

basic

mod

el+GLSgeminus15

451

003lowast

Basic

mod

el074

(062ndash086)

mdashmdash

Basic

mod

elversus

basic

mod

el+cTnTtimes100

987

0003lowast

Basic

mod

el+GLSgeminus15

081

(069ndash

091)

mdash004lowast

Basic

mod


basic

mod


690

000

9lowastBa

sicmod

el+cTnTtimes100

082

(071ndash091)

mdash003lowast

Basic

mod


basic

mod


453

004

6lowastBa

sicmod


089

(077ndash095)

mdash0001lowast

Basic

mod

elversus

basic

mod


1140

0002lowast

Firstweinclu

dedbackgrou

ndhypertensio

nandplasmaalbu

min

concentrationbu

texcludeddiabetes

andcoronary

arteria

ldise

asebasedon

finalredu

cedmod

elof

Table4

andstu

died

theadditio

nalp

redictive

values


snegativeGLS


enw

einclu

deddiabetes

andcoronary

arteria

ldise

asein

additio

nto

hypertensio

nandserum

albu

min

concentrationto

constructthe

basic

mod

elbecausethey

arecommon

lyused

forr

iskstr

atificatio

nin

thehemod

ialysis

popu

latio

nandstu

died

theadditio

nalp

redictivevalues


snegativeGLS


119875lt005

com

parin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndhypertensio

nandplasmaa

lbum

inconcentration

comparin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndcoronary

arteria

ldise

asediabetes

andhypertensio

nandplasmaa

lbum

inconcentration

Abbreviatio

nsA

UC

area

underc

urveC

Iconfi

denceintervalcTnT

cardiac

tropo

ninT

GLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in














Acknowledgments




References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















119875 Variables 119903119904119875







4 Discussion







Table4Cox

regressio

nanalysisfora

ll-causem

ortality

Basic

mod

elBa

sicmod

el+

cTnTtimes100

Basic

mod

el+

GLSgeminus15

Fullmod

elFu

llmod

el+

interactionterm

Redu

cedmod

el1

Redu

cedmod

el2

(finalm

odel)

Finalm

odel+

interactionterm

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR

119875

Album

in017

000

4lowast022

010

016

0003lowast

023

0047lowast

028

009

022

004lowast

024

004

8lowast029

009

CAD

262

004lowast

243

004lowast

196

016

212

012

222

011

221

010

mdashmdash

mdashmdash

DM

317

003lowast

210

035

297

004lowast

172

040

149

050

mdashmdash

mdashmdash

mdashmdash

HTN

339

002lowast

294

005lowast

309

002lowast

309

003lowast

264

009

300

004lowast

270

006

231

012

cTnTtimes100

mdashmdash

116

0001lowast

mdashmdash

113

000

9lowast119

001lowast

115

0001lowast

114

0002lowast

121

0001lowast

GLSgeminus15

mdashmdash

mdashmdash

357

002lowast

309

003lowast

400

007

337

002lowast

279

0049lowast

645

001lowast

(cTn

Ttimes100)

(GLSgeminus15)

mdashmdash

mdashmdash

mdashmdash

mdashmdash

091

022

mdashmdash

mdashmdash

090

014


theCox

regressio

nanalysis

95

CIsfor

each

HRarep

resented

inSupp

lementary

TableS

3In

multiv

ariateanalysis

wefi

rstly

constructedthemod

elinclu

ding

backgrou

ndcoronary

arteria

ldise

ase(C

AD)a

nddiabetes

andhypertensio

ntogether

with

serum

albu

min

concentrationas

abasic

mod

elthen


aGLSgeminus15

into

thebasic

mod

elto

study

theire

ffects


pwise

procedurewas

used

tochoo

sethefin

alredu

cedmod

elwith

varia

bles


inthemod

elTo

obtain

anadequateredu

cedmod

elbefore

drop

ping

acovariatefro

mthem

odel

wec

onfirmed

thatits

absenced

idno

tresultinas

ubstantia

lchangeintheo

verallpredictin

gpo

wer

ofthem

odel

lowast

119875lt005(cTn

Ttimes100)


Abbreviatio

nsC

ADcoron

aryarteria

ldise

asecTnT

cardiac

tropo

ninTDMdiabetesGLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in(a

lessnegativ

eGLS

was

defin

edby

aGLSgeminus15)


Table5Ad

ditio

nalpredictivev

alueso

fcTn

Ttimes100andles

snegativeG

LS(geminus15)form

ortalityusingCox

regressio

nmod

elsa

nalysis

andRO

Ccurvea

nalysis

Thea

ddition

alvalueo

fcTn

Ttimes100andles

snegativeG

LS(geminus15)inmod

elpredictio

nform

ortalityusingCox

regressio

nmod

elsanalysiswith

analysis

ofdeviance

Thea

ddition

alpredictiv

evalue


snegativeG

LS(geminus15)b

ased

onRO

Ccurvea

nalysis

with

calculated

AUCs

Chi-s

quare119875

AUC

95CI

119875

119875

Album

in+hypertensio


albu

min

+hypertensio


988

0002lowast

Album

in+hypertensio

n068

(053

ndash081)

mdashmdash

Album

in+hypertensio


albu

min

+hypertensio


456

005lowast

Album

in+hypertensio

n+GLSgeminus15

077

(065ndash088)

003lowast

mdash

Album

in+hypertensio

n+cTnTtimes100

078

(06ndash0

89)

002lowast

mdashAlbum

in+hypertensio


085


mdashBa

sicmod

elversus

basic

mod

el+GLSgeminus15

451

003lowast

Basic

mod

el074

(062ndash086)

mdashmdash

Basic

mod

elversus

basic

mod

el+cTnTtimes100

987

0003lowast

Basic

mod

el+GLSgeminus15

081

(069ndash

091)

mdash004lowast

Basic

mod


basic

mod


690

000

9lowastBa

sicmod

el+cTnTtimes100

082

(071ndash091)

mdash003lowast

Basic

mod


basic

mod


453

004

6lowastBa

sicmod


089

(077ndash095)

mdash0001lowast

Basic

mod

elversus

basic

mod


1140

0002lowast

Firstweinclu

dedbackgrou

ndhypertensio

nandplasmaalbu

min

concentrationbu

texcludeddiabetes

andcoronary

arteria

ldise

asebasedon

finalredu

cedmod

elof

Table4

andstu

died

theadditio

nalp

redictive

values


snegativeGLS


enw

einclu

deddiabetes

andcoronary

arteria

ldise

asein

additio

nto

hypertensio

nandserum

albu

min

concentrationto

constructthe

basic

mod

elbecausethey

arecommon

lyused

forr

iskstr

atificatio

nin

thehemod

ialysis

popu

latio

nandstu

died

theadditio

nalp

redictivevalues


snegativeGLS


119875lt005

com

parin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndhypertensio

nandplasmaa

lbum

inconcentration

comparin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndcoronary

arteria

ldise

asediabetes

andhypertensio

nandplasmaa

lbum

inconcentration

Abbreviatio

nsA

UC

area

underc

urveC

Iconfi

denceintervalcTnT

cardiac

tropo

ninT

GLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in














Acknowledgments




References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table4Cox

regressio

nanalysisfora

ll-causem

ortality

Basic

mod

elBa

sicmod

el+

cTnTtimes100

Basic

mod

el+

GLSgeminus15

Fullmod

elFu

llmod

el+

interactionterm

Redu

cedmod

el1

Redu

cedmod

el2

(finalm

odel)

Finalm

odel+

interactionterm

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR119875

HR

119875

Album

in017

000

4lowast022

010

016

0003lowast

023

0047lowast

028

009

022

004lowast

024

004

8lowast029

009

CAD

262

004lowast

243

004lowast

196

016

212

012

222

011

221

010

mdashmdash

mdashmdash

DM

317

003lowast

210

035

297

004lowast

172

040

149

050

mdashmdash

mdashmdash

mdashmdash

HTN

339

002lowast

294

005lowast

309

002lowast

309

003lowast

264

009

300

004lowast

270

006

231

012

cTnTtimes100

mdashmdash

116

0001lowast

mdashmdash

113

000

9lowast119

001lowast

115

0001lowast

114

0002lowast

121

0001lowast

GLSgeminus15

mdashmdash

mdashmdash

357

002lowast

309

003lowast

400

007

337

002lowast

279

0049lowast

645

001lowast

(cTn

Ttimes100)

(GLSgeminus15)

mdashmdash

mdashmdash

mdashmdash

mdashmdash

091

022

mdashmdash

mdashmdash

090

014


theCox

regressio

nanalysis

95

CIsfor

each

HRarep

resented

inSupp

lementary

TableS

3In

multiv

ariateanalysis

wefi

rstly

constructedthemod

elinclu

ding

backgrou

ndcoronary

arteria

ldise

ase(C

AD)a

nddiabetes

andhypertensio

ntogether

with

serum

albu

min

concentrationas

abasic

mod

elthen


aGLSgeminus15

into

thebasic

mod

elto

study

theire

ffects


pwise

procedurewas

used

tochoo

sethefin

alredu

cedmod

elwith

varia

bles


inthemod

elTo

obtain

anadequateredu

cedmod

elbefore

drop

ping

acovariatefro

mthem

odel

wec

onfirmed

thatits

absenced

idno

tresultinas

ubstantia

lchangeintheo

verallpredictin

gpo

wer

ofthem

odel

lowast

119875lt005(cTn

Ttimes100)


Abbreviatio

nsC

ADcoron

aryarteria

ldise

asecTnT

cardiac

tropo

ninTDMdiabetesGLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in(a

lessnegativ

eGLS

was

defin

edby

aGLSgeminus15)


Table5Ad

ditio

nalpredictivev

alueso

fcTn

Ttimes100andles

snegativeG

LS(geminus15)form

ortalityusingCox

regressio

nmod

elsa

nalysis

andRO

Ccurvea

nalysis

Thea

ddition

alvalueo

fcTn

Ttimes100andles

snegativeG

LS(geminus15)inmod

elpredictio

nform

ortalityusingCox

regressio

nmod

elsanalysiswith

analysis

ofdeviance

Thea

ddition

alpredictiv

evalue


snegativeG

LS(geminus15)b

ased

onRO

Ccurvea

nalysis

with

calculated

AUCs

Chi-s

quare119875

AUC

95CI

119875

119875

Album

in+hypertensio


albu

min

+hypertensio


988

0002lowast

Album

in+hypertensio

n068

(053

ndash081)

mdashmdash

Album

in+hypertensio


albu

min

+hypertensio


456

005lowast

Album

in+hypertensio

n+GLSgeminus15

077

(065ndash088)

003lowast

mdash

Album

in+hypertensio

n+cTnTtimes100

078

(06ndash0

89)

002lowast

mdashAlbum

in+hypertensio


085


mdashBa

sicmod

elversus

basic

mod

el+GLSgeminus15

451

003lowast

Basic

mod

el074

(062ndash086)

mdashmdash

Basic

mod

elversus

basic

mod

el+cTnTtimes100

987

0003lowast

Basic

mod

el+GLSgeminus15

081

(069ndash

091)

mdash004lowast

Basic

mod


basic

mod


690

000

9lowastBa

sicmod

el+cTnTtimes100

082

(071ndash091)

mdash003lowast

Basic

mod


basic

mod


453

004

6lowastBa

sicmod


089

(077ndash095)

mdash0001lowast

Basic

mod

elversus

basic

mod


1140

0002lowast

Firstweinclu

dedbackgrou

ndhypertensio

nandplasmaalbu

min

concentrationbu

texcludeddiabetes

andcoronary

arteria

ldise

asebasedon

finalredu

cedmod

elof

Table4

andstu

died

theadditio

nalp

redictive

values


snegativeGLS


enw

einclu

deddiabetes

andcoronary

arteria

ldise

asein

additio

nto

hypertensio

nandserum

albu

min

concentrationto

constructthe

basic

mod

elbecausethey

arecommon

lyused

forr

iskstr

atificatio

nin

thehemod

ialysis

popu

latio

nandstu

died

theadditio

nalp

redictivevalues


snegativeGLS


119875lt005

com

parin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndhypertensio

nandplasmaa

lbum

inconcentration

comparin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndcoronary

arteria

ldise

asediabetes

andhypertensio

nandplasmaa

lbum

inconcentration

Abbreviatio

nsA

UC

area

underc

urveC

Iconfi

denceintervalcTnT

cardiac

tropo

ninT

GLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in














Acknowledgments




References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table5Ad

ditio

nalpredictivev

alueso

fcTn

Ttimes100andles

snegativeG

LS(geminus15)form

ortalityusingCox

regressio

nmod

elsa

nalysis

andRO

Ccurvea

nalysis

Thea

ddition

alvalueo

fcTn

Ttimes100andles

snegativeG

LS(geminus15)inmod

elpredictio

nform

ortalityusingCox

regressio

nmod

elsanalysiswith

analysis

ofdeviance

Thea

ddition

alpredictiv

evalue


snegativeG

LS(geminus15)b

ased

onRO

Ccurvea

nalysis

with

calculated

AUCs

Chi-s

quare119875

AUC

95CI

119875

119875

Album

in+hypertensio


albu

min

+hypertensio


988

0002lowast

Album

in+hypertensio

n068

(053

ndash081)

mdashmdash

Album

in+hypertensio


albu

min

+hypertensio


456

005lowast

Album

in+hypertensio

n+GLSgeminus15

077

(065ndash088)

003lowast

mdash

Album

in+hypertensio

n+cTnTtimes100

078

(06ndash0

89)

002lowast

mdashAlbum

in+hypertensio


085


mdashBa

sicmod

elversus

basic

mod

el+GLSgeminus15

451

003lowast

Basic

mod

el074

(062ndash086)

mdashmdash

Basic

mod

elversus

basic

mod

el+cTnTtimes100

987

0003lowast

Basic

mod

el+GLSgeminus15

081

(069ndash

091)

mdash004lowast

Basic

mod


basic

mod


690

000

9lowastBa

sicmod

el+cTnTtimes100

082

(071ndash091)

mdash003lowast

Basic

mod


basic

mod


453

004

6lowastBa

sicmod


089

(077ndash095)

mdash0001lowast

Basic

mod

elversus

basic

mod


1140

0002lowast

Firstweinclu

dedbackgrou

ndhypertensio

nandplasmaalbu

min

concentrationbu

texcludeddiabetes

andcoronary

arteria

ldise

asebasedon

finalredu

cedmod

elof

Table4

andstu

died

theadditio

nalp

redictive

values


snegativeGLS


enw

einclu

deddiabetes

andcoronary

arteria

ldise

asein

additio

nto

hypertensio

nandserum

albu

min

concentrationto

constructthe

basic

mod

elbecausethey

arecommon

lyused

forr

iskstr

atificatio

nin

thehemod

ialysis

popu

latio

nandstu

died

theadditio

nalp

redictivevalues


snegativeGLS


119875lt005

com

parin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndhypertensio

nandplasmaa

lbum

inconcentration

comparin

gtheA

UCof

indicatedmod

elwith

thatof

them

odelinclu

ding

backgrou

ndcoronary

arteria

ldise

asediabetes

andhypertensio

nandplasmaa

lbum

inconcentration

Abbreviatio

nsA

UC

area

underc

urveC

Iconfi

denceintervalcTnT

cardiac

tropo

ninT

GLS

globalleft

ventric

ular

peak

systo

liclong

itudinalstra

in














Acknowledgments




References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





























Acknowledgments




References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















References





































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Clinical Study Independent Value of Cardiac Troponin T and ...

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Transcript of Clinical Study Independent Value of Cardiac Troponin T and ...