Comparative study of circulating cardiac biomarkers galectin-3 and troponin I in patients with heart failure
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https://www.eduzhai.net Clinical M edicine and Diagnostics 2013, 3(4): 92-100 DOI: 10.5923/j.cmd.20130304.04 Comparative Study of Circulating Cardiac Biomarker Galectin-3 and Troponin I in Heart Failure Patients Hanan Mahmoud Fayed1,*, Mohamed Abdelrazek Alsenbesy2, Tahia Hashim Saleem3 , Marwa Abd-elhady Ahmed2 1clinical and chemical pathology department- Qena faculty of medicine-South Valley University 2Internal M edicine department-Qena faculty of medicine- South Valley University 3Biochemistry department-Assuit faculty of medicine-Assuit University Abstract heart failure (HF) is a major growing health prob lem. Galectin -3 associated with fibrosis, inflammation and cardiac remodeling. There is increasing interest in the ro le of circulating card iac troponin in detecting myocardial inju ry. So our aim was to determine serum values of Galectin -3 and troponin-I in hospitalized HF patients with different severity grades and correlate results with clin ical, echocardiography in a cross sectional case-control study of fifty cases with HF fro mboth sexes on standard medication. Thirty healthy volunteers’ subjects selected as controls. HF severity grade classified according to New York Heart Association; 8(16%) class II and 42(84%) class (III+IV). Left ventricular ejection fraction (LVEF) ≤ 40% in 23(46%) o f HF. Co mpared to controls; Galectin -3 and troponin-I were significantly higher (18.40 ±11.5 ng/ ml) vs (5.75 ±1.427 ng/ml); (p<0.001); (0.429± 0.630 ng/ ml) vs (0.019±0.0544 ng/ml); (p= 0.004) respectively. Receiver operating characteristic (ROC) analysis for Galect in-3 showed the best cut off point wh ich discriminates between disease and normal at Galect in-3 (≥7.36 ng/ml) with sensitivity 74%, specificity 96.7%, area under the curve (AUC) of 0.876 (p<0.0001), positive predictive value (PPV) 94.87% and negative predict ive value (NPV) 68.29%. ROC analysis for troponin-I positivity shows 56% sensitivity, 86.67% specificity, PPV 87.5% and NPV 54.17%. Whereas combined[troponin-I positivity + Galect in-3] showed 84% sensitivity, 80 % specificity, PPV 87.5% and NPV 75% i.e. improve Galectin-3 sensitivity and the negative predicator value. So results support combined markers assessment in predicting severity in HF patients with preserved LVEF. Keywords Card iac Bio markers, Galect in-3, Heart Failure, Troponin I, Anemia, Echocardiography, Uric Acid, Fibrosis, Re modeling 1. Introduction Heart failure (HF) is a c linica l syndrome characterized by inadequate systemic perfusion to meet the body’s metabolic demands as a result of impaired cardiac function. After the initial insult to the myocardiu m, HF is a disease with autonomic progression associated with ventricular dysfunction and cardiac remodeling. The functional changes associated with HF can be systolic and/or diastolic in nature. HF has long been considered as irreversible and amenable only to palliative therapy. However, the idea of chronic HF as an irrevers ib le end -st age p rocess is challenged by e xp er i men t al an d c l in ica l ev id en ce o f a p o s s ib le improve ment in the intrinsic defects of function and structure (afflict ing the failing heart) following therapeutic intervention in the earliest phase of the cardiac alteration. * Corresponding author: email@example.com (Hanan Mahmoud Fayed) Published online at https://www.eduzhai.net Copyright © 2013 Scientific & Academic Publishing. All Rights Reserved Early diagnosis of HF depends on the availability of specific, accurate and effective markers of disease. A cardiovascular bio marker can be classified into different types, according to its pathophysiological characteristics and/or clinical use after the initial insult to the myocardium . Galect in-3 (Gal-3) a macrophage-derived mediator that induces cardiac fibroblast proliferat ion, collagen deposition and ventricular dysfunction; thus it plays an important regulatory role in cardiac fib rosis and remodeling, which are key contributing mechanisms to the development and progression of HF. Besides fibrosis, Gal-3 plays an important role in the inflammatory responses which are important players in the process of cardiac remodeling. Gal-3 is specifically up regulated in decompensated HF compared with co mpensated HF in animal models; even before the onset of frank HF. Moreover; Gal-3 up regulation may be a general phenomenon in left ventricular d y s fun ctio n . In HF, there is increased o xidative stress because of generation of reactive o xygen mo lecules and decrease in endogenous antioxidants which is responsible for endothelial Clinical M edicine and Diagnostics 2013, 3(4): 92-100 93 dysfunction and progression of HF. Seru m uric acid; a simp le and readily available indirect b io marker of o xidative stress resulting fro m increased xanthine o xidase activity. It correlates with impaired hemodynamic and predicts adverse prognosis in heart failure. Card iac troponin (cTn) co mplex involved in the regulation of cardiac muscle contraction; the fact that they are strictly intracellular proteins which are not found in the circulation of healthy indiv iduals provides a high level of clinical sensitivity and specificity even when cardiac lesions are small. Thus, any significantly detectable troponin in circulat ion is considered a sign of acute myocardial cell damage. cTn in blood is the preferred bio markers of myocardial injury; these are released as a result of severe ischemia and also as consequence of stress, injury secondary to increased inflammation, o xidative stress and neurohormonal activation. Modest elevations of cTn levels are also found in patients with HF without ischemia; and congestive HF. The mechanis m for this elevation is believed to be due to ongoing myocyte in jury and progressive loss of cardiac myocytes; hence releasing cTn into the circulation. 2. The Aims of This Study were to 1) Determine the value of plas ma Galectin-3 and Troponin I in HF patients. 2) Assess some morb idity associated cofactors in HF patients such as hypernatraemia, hyperuricemia and anemia. 3) Correlate laboratory results with the clinical severity and the echocardiography findings. 3. Patients and Methods A cross sectional case/control study was conducted (after approval fro m medical ethics co mmittee) on fifty patients (after obtaining informed consent) having the inclusion criteria fro m both sexes, who attended the Qena university hospital for one year. Inclusion criteria: Any patient with clin ical manifestations of HF (either acute or chronic) with age above 18 years old who agree to participate in this study. Exclusion criteria: Patients's with associated with hepatic or renal diseases and refuse to participate in this study. HF severity grade was classified according to clinical symptoms by the New Yo rk Heart Association (NYHA). Echocardiogram performed to all patients for ischemia, hypertension or arrhythmia utilizing two-d imensional (2D) cardiovascular ultrasound system t ransthoracic (using Viv id 3, 2005, Germany, syncmaster450 M B) to assess cardiac chamber dimension, systolic and diastolic function, ejection fraction (Current practice uses two dimensional measurement to calculate LVEF with the Simpson’s Biplane method; tracing the endocardial border at end diastole and end systole to estimate left ventricle (LV) volu mes and LVEF), regional wall motion abnormalities, valve heart disease, cardiomyopathies. A 30 healthy age and sex matched subjects selected as control. 10 ml venous blood drawn fro m all patients and controls then divided into:- • 5 ml in plain tube; centrifuged at 3,500 rp m for 15 min at 4 °C; the serum transferred into two of 1 ml cryotubes and stored at -80 °C for later analyses. • Rest of seru m used for spectrophotometric measurements of serum urea, creatin ine, u ric acid, Sodiu m and albumin;[Cobas C311 (Roche diagnostics, Germany)]. • Estimated glo meru lar filtration rate (eGFR); as an indicator of renal function estimated fro m seru m creat inine using a formula that accounts for the influence of age on creatinine production, wh ich was validated in patients with HF, and described in detail in modificat ion of d iet and renal disease (MDRD). • 1.8 ml b lood on citrate tubes for measurements of prothrombin time & concentration. • 3 ml b lood on EDTA for Co mp lete blood count "CBC" (Cell Dyn 1800-Abbott diagnostics). • Troponin I tested as instructed by the manufacturers using commercial automated chemilu minescent micropart icle immune assay (CMIA ) utilizing Chemi-Flex Technology (Architect i2000, Abbott diagnostics, USA). Normal value ≤0.30 ng/ ml. The Arch itect STAT Troponin-I assay is a two-step immunoassay, in the first step, sample, assay diluent and anti-troponin-I antibody-coated paramagnetic microparticles (mouse, monoclonal) are combined. Troponin-I present in the sample binds to the anti-troponin-I coated microparticles. After incubation and wash, anti-troponin-I acridin iu m-labeled (mouse, monoclonal) conjugate was added in the second step. Following another incubation and wash, pre-trigger and trigger solutions are then added to the reaction mixture. The resulting chemi-lu minescent reaction was measured as relative light units (RLUs). A d irect relat ionship exists between the amount of troponin-I in the sample and the RLUs detected by the Architect i System optics. The concentration of troponin-I is read relative to a standard curve established with calibrators of known t roponin-I co n centratio n s . • Galectin-3 levels determined using co mmercially available enzy me-linked immune-sorbent assay (human galectin-3 ELISA) kit (W KEA M ED supplies corp. USA) according to manufacturer’s protocol [provided by WKEA MED supplies corp. New York. USA] and were measured on thermo scientific mu lt iskan EX microplate photomter reader. Normal value: 0.7-22ng/ ml. Calibration of the assay was performed according to the manufacturer’s recommendations and values were normalized to a standard curve. This assay has high sensitivity (lower limit of detection 1.13ng/ mL) and exhib its no cross-reactivity with collagens or other members of the galectin family. Co mmonly used HF medication; like angiotensin-converting enzy me (A CE) inhibitors, beta-blockers, spironolactone, furosemide, acetyl-salicylic acid, warfarin, cou marines and 94 Hanan M ahmoud Fayed et al.: Comparative Study of Circulating Cardiac Biomarker Galectin-3 and Troponin I in Heart Failure Patients digoxin have no interference with the assay. • Statistical anal yses: Analysis of data was done using SPSS (statistical program for social science version 20 as fo llo ws : Description of quantitative variab les as mean ± SD and range Description of qualitative variables as nu mber and percentage Unpaired t-test was used to compare quantitative variables, in parametric data (SD<50% mean) One way ANOVA test was used to compare more than two groups as regard quantitative variables by comparison of means across quartiles of galectin-3 Chi-s quare test was used to compare two groups as regard qualitative variables Pearson Correlati on was used to rank variables in correlation with Gal-3 and ctn I. Recei ver operator characteristic curve (ROC) analysis was performed. (Clinton et al., 1992)18 to find out the best cut off value of Gal-3 and troponin I to validate parameters as follow: Sensitivity = true positive / (true positive + false negative) = ability of the test to detect positive cases. Specificity = t rue - negative / (true negative + false positive) = ability of the test to exclude negative cases. Positive predictive value (PPV) = true positive / (true positive +false positive) = % o f true positive cases to all p o s itiv e. Negative predictive value (NPV) = true negative /true negative + false negative = % o f the t rue negative to all negative cases P value >0.05 insignificant, P<0.05 significant and P<0.01 highly significant 4. Results The demographic characteristics and clinical data of all HF cases (table 1); the mean age 54.02±14.7 years, 27(54%) females and 23(64%) males. 8(16%) of HF patients was NYHA-class II and 42(84%) were class III and IV. 23(46%) of patients had LVEF ≤ 40%. All cases have dyspnea 50(100%), 19(38%) were Smokers, 36 (72%) had edema, 33(66%) had crepitations, 19(38%) with raised JVP and 19(38%) had hepatomegaly. Hypertension presents in 6(12%) of cases while anemia presents in 21(42%) of patients, 15(30%) were diabetics & 27(54%) had IHD, 10(20%) had COPD, 13(26%) had AF. A ll patients were on standard med ication fo r HF, including beta blockers comb ined with ACEI were taken by 41(82%) of patients were as diuretics combined with A CEI were taken by 44(88%) of patients. A statistically significant difference between cases and controls; in relation to values of SBP, DBP, LVDD, Hb, Prothromb in Time, urea, eGFR, uric acid, Troponin I and galectin-3[table 2]. Table 1. Medical history of heart failure group Pat ient group (No= 50) Sex • Male • Female • II NYHA • III • IV Smoking • Yes • No Dyspnea • Yes • No Oedema • Yes • No Crep itat ion • Yes • No Jugular venous pressure • Yes • No COPD • Yes • No RALES • Yes • No Atrial fibrillat io n • Yes • No Ischemic heart • Yes disease • No Anemia • Yes • No Hypertension • Yes • No Hepatomegaly • Yes • No Diabet es Mellit us • Yes • No Left ventricular Eject io n Fract io n •≤ 40% • > 40% Medicat io n s: Beta • Yes • No adrenergic antagonist + ACE inhibitor Diuret ics + • Yes • No ACE inhibitor Number 23 27 8 27 15 19 31 50 0 36 14 33 17 19 31 10 40 21 29 13 37 27 23 21 29 6 44 19 31 15 35 23 27 41 9 44 6 P ercent age 46% 54% 16% 54% 30% 38% 62% 100% 0% 72% 28% 66% 34% 38% 62% 20% 80% 42% 58% 26% 74% 54% 46% 42% 58% 12% 88% 38% 62% 30% 70 % 46% 54% 82% 18% 88% 12% Table 2. Clinical and laboratory data of studied groups Variable Age (y) SBP (mmHg) DBP(mmHg) LVDD Hb (g/dl) P T (sec) S. Urea S. Creat eGFR S. Uric acid S. Albumin Na Troponin I Galect in -3 *Significant Cases (N=50) 54.02±14.7 105.02±20.9 68.0±13.2 5.47±1.28 11.75±2.78 13.07±1.45 41.9±13.6 0.9±0.27 80.66±29.4 6.56±2.00 3.71±0.63 135±4.9 0.429±0.63 18.40±11.5 Con trol (N=30) 36.7±12.3 113.5±8.62 75.16±5.9 3.96±0.43 13.2±1.09 12.98±0.84 16.1±2.8 0.57±0.23 157.56±72.1 4.073±1.74 4.65±0.57 139±3.23 0.019±0.054 5.75±1.43 F 0.018 15.58 10.81 31.7 7.24 8.43 32.46 0.565 41.6 8.602 0.338 1.202 9.015 50.28 P 0.893 0.001* 0.002* <0.001* 0.009* 0.005* <0.001* 0.455 <0.001* 0.004* 0.563 0.276 0.004* <0.001* Clinical M edicine and Diagnostics 2013, 3(4): 92-100 95 Baseline clinical and laboratory characteristics of HF patients grouped by quartile of gal-3 levels; Gal-3 had a high statistical significant levels with alterat ion of SBP (p<0.001), DBP (p <0.001), LVDD (p<0.001) and the presence of ischemic heart disease (p=0.003)[table 3]. Table 3. Clinical and laboratory characterist ics of HF pat ient s by quart ile galect in-3 levels Variable Age Sex • Male (23) Female (27) NYHA • II (8) • III (27) • IV (15) Smoking • Yes (19) • No (31) Oedema • Yes (36) • No (14) Crep itat ion s • Yes (33) • No (17) JVP • Yes (19) • No (31) COPD • Yes (10) • No (40) RALES • Yes (21) • No (29) AF • Yes (13) • N0 (37) Ischemic heart disease • Yes (27) • No (23) Anemia • Yes (18) • No (32) Hypertension • Yes (6) • No (44) Hepatomegaly • Yes (19) • No (31) DM • Yes (15) • No (35) Medicat io n s: • BB + ACEI • Diuretics + ACEI SBP (mm Hg) DBP(mmHg) LVDD(cm) LVEF (%) eGFR Urea Creat in ine Uric acid Albumin 1 (<13.63 ) No (17) 50±15.1 5(21.74) 12(44.44) 4(50) 9(33.33) 4(26.67) 6(31.58) 11(35.48) 11(30.56) 6(42.86) 13(39.39) 4(23.530) 7(36.84) 10(32.26) 7(70%) 10(25%) 7(33.33) 10(34.48) 6(46.15) 11(29.73) 4(14.81) 13(56.52) 5(27.78) 12(37.5) 3(50) 14(31.82) 7(36.84) 10(32.26) 5(33.33) 12(34.285) 13(76.47) 16(94.12) 120.6±22.4 77.3±13.9 4.68±0.51 58.91±5.90 83±34.0 40.4±14.35 0.86±0.29 6.194±1.98 3.70+0.83 Galectin-3 quartile (ng/ml) No(%) 2 3 (13.63-17.63) (17.64-21.62) No (15) No (1) 57.5±11.6 75 9(39.13) 6(22.22) 1(4.35) 0(0) 3(37.5) 9(33.33) 3(20) 0(0) 1(3.71) 0(0) 7(36.84) 8(25.81) 1(5.26) 0(0) 11(30.56) 4(28.57) 9(27.27) 6(35.29) 1(2.78) 0(0) 0(0) 1(5.88) 5(26.32) 10(32.26) 0(0) 1(3.2) 1(10%) 14(35%) 0(0) 1(2.5) 5(23.81) 10(34.48) 1(4.76) 0(0) 5(38.46) 10(27.03) 0(0) 1(2.7) 9(33.33) 6(26.09) 1(3.71) 0(0) 7(38.89) 8(25) 0(0) 1(3.13) 1(16.67) 14(31.82) 0(0) 1(2.27) 6(31.58) 9(29.03) 0(0) 1(3.22) 5(33.33) 10(28.57) 0(0) 1(2.86) 12(80) 12(80) 102.6±13.9 66.33±9.15 5.11±0.922 43.73±7.303 72.8±26.22 44.73±15.38 1.05±0.297 6.973±1.54 3.66±0.515 1(100) 1(100) 80 50 5.7 38.00 94 28 0.80 8.100 4.20 4 (>21.62) No (17) 52.8±16.2 8(34.78) 9(33.34) 1(12.5) 8(29.63) 8(53.33) 5(26.32) 12(38.71) 13(36.10) 4(28.57) 11(33.33) 6(35.294) 7(36.84) 10(32.26) 2(20) 15(37.5) 8(38.1) 9(31.04) 2(15.38) 15(40.54) 13(48.15) 4(17.39) 6(33.33) 11(34.37) 2(33.33) 15(34.09) 6(31.58) 11(35.48) 5(33.33) 12(34.285) 15(88.23) 15(88.23) 92.9±14.3 61.17±10.08 6.57±1.41 28.82±7.58 84.4±28.2 41.6±11.7 0.88±0.209 6.46±2.42 3.74±0.522 P value 0.292 0.236 0.502 0.441 0.797 0.388 0.826 0.060 0.567 0.429 0.012* 0.653 0.778 0.858 0.916 0.787 0.648 <0.001* <0.001* <0.001* <0.001* 0.658 0.613 0.197 0.622 0.873 96 Hanan M ahmoud Fayed et al.: Comparative Study of Circulating Cardiac Biomarker Galectin-3 and Troponin I in Heart Failure Patients PT (seconds) P C (%) Na (mmol/l) Hb (gm/dl) *Significant 12.7±1.52 13.5±1.52 13.8 12.9±1.30 0.382 83.8±15 75.5±11.6 88 79.2±8.9 0.249 135.3±5.70 135.0±5.29 141 134.3±4.02 0.622 12.4±1.9 12.09±1.9 16 12.47±2.2 0.347 Gal-3 had a high significant positive correlation with SBP (r=0.576; p<0.001), DBP (r=0.554; p<0.001), LVDD (r=0.699; p<0.001) and the presence of ischemic heart disease (r=0.407; p =0.003) [table 4]. Table 4. Correlation between clinical and laboratory findings with galectin-3 and troponin I Galect in -3 Troponin I Variable r p-value r p-value Age Sex Creat in ine Urea Uric acid Albumin PT PC Na eGRF SBP DBP LVDD IHD Anemia Oedema Crep itat ion AF Heart sound JVP RALES COPD DM Smoking 0.012 0.127 0.028 0.042 0.50 0.060 0.027 0.088 0.138 0.020 0.576 0.554 0.699 0.407 0.033 0.029 0.158 0.266 0.187 0.072 0.058 0.271 0.049 0.081 0.934 0.381 0.845 0.774 0.730 0.679 0.851 0.544 0.337 0.889 <0.001* <`0.001* <0.001* 0.003* 0.328 0.844 0.275 0.062 0.194 0.618 0.690 0.057 0.739 0.578 0.004 0.106 0.88 0.009 0.562 0.185 0.046 0.077 0.009 0.204 0.020 0.028 0.151 0.106 0.107 0.050 0.115 0.002 0.113 0.021 0.135 0.009 0.061 0.020 0.977 0.462 0.543 0.953 0.246 0.199 0.751 0.594 0.950 0.156 0.888 0.849 0.296 0.462 0.460 0.732 0.426 0.990 0.432 0.881 0.350 0.952 0.673 0.882 In our study; receiver-operating characteristic (ROC) to test accuracy analysis for galectin-3 shows that the best cut off point wh ich discriminates between disease and normal is galectin-3 ≥7.36 with sensitivity 74% and specificity 96.7% and area under the curve (AUC) o f 0.876 (p<0.0001) and positive predictive value (PPV) 94.87% and negative predictive value (NPV) 68.29%. And ROC analysis for troponin I positivity shows 56% sensitivity & 86.67% specificity and PPV 87.5% and NPV 54.17%. Whereas combined[Troponin I positivity + galectin-3 at (≥ 7.36 ng/ml)] shows 84% sensitivity & 80 % specificity and PPV 87.5% and NPV 75%[figure 1, table 5& 6]. Figure 1. ROC curve Table 5. Posit ivit y rat es (≥7.36ng/ml) of Troponin I, Galect in-3 and their combined assay Variable Troponin I Galectin- 3 Negat iv e Po sit ive Negat iv e Po sit ive Cases 22 28 13 37 Con trol 26 4 28 2 Chi-sq uare 14.22 34.025 p-value <0.001* <0.001* Combined Negative 8 Troponin I + Positive 42 G alectin-3 24 6 32.00 <0.001* * Significant Table 6. Sensitivity, specificity, positive and negative predictive value of Galectin-3, Troponin I and combined[Galectin-3 +Troponin I] Hepatomegaly Hypertension * Significant 0.022 0.133 0.879 0.356 0.129 0.217 0.362 0.129 Variable Galect in -3 Troponin I Combined cT n I + Gal-3 Sensiti vity 74% 56% 84% S peci fi city 93.33% 86.67% 80% PPV 94.87% 87.5% 87.5% NPV 68.29% 54.17% 75% Clinical M edicine and Diagnostics 2013, 3(4): 92-100 97 Variable Hb Min- Max Mean ±SD Table 7. hemoglobin and serum uric acid levels among cases & controls according to gender HF cases No (50) Males Females No (23) No (27) Controls No (30) Males Females No (15) No (15) 7.0-16.9 11.63±2.9 7.0-16.0 11.86±2.7 12.0-15.0 14.02±0.8 11.5-14.5 12.5-0.8 P value <0.001* s. uric acid Min- Max Mean ±SD 2.9-11.3 7.3±1.8 3.6-11.0 6.4±2.1 1.6-6.2 3.7±1.26 3.20-7.80 4.43±1.43 <0.001* * Significant In our study; a statistically significant low Hb levels among HF patients with a mean ± SD Hb leve l a mong males of (11.63±2.9) & (11.86±2.7) among females compared to controls, (14.02±0.8) males and (12.5±0.8) females respectively. A statistically significant high serum uric acid levels among HF patients with a mean ±SD uric acid level among males (7.3±1.8) and among females (6.4±2.1) compared to controls (3.7±1.26) males and (4.43±1.43) females respectively[table 7]. 5. Discussion It is clear that management of HF patients is a huge burden therefore, it is imperative to appropriately risk-stratify patients to identify those who need the closest follow-up. Traditional risk factors such as age, diabetes, and smoking, as well as sympto m severity, can all indicate those at risk. However, these alone are often inadequate to stratify risk. As a result, novel blood-based biomarkers e.g. Gal-3 is directly involved in the patho-physiology of cardiac injury and progression to HF(19,20). Moreover, gal-3 appears to have direct clinical relevance in aiding diagnosis, risk stratification and prognosticate patients with HF, mon itoring therapy, therapeutic modificat ion and treating to targets in order to improve clin ical outcomes. In our study; gal-3 and cTn I plasma levels were statistically significant higher in subjects with HF co mpared to control with mean gal-3 (18.40 ±11.5 ng/ml) among HF patients and (5.75 ±1.427 ng/ ml) among control group (p value <0.001). And mean cTn I (0.429± 0.630 ng/ml) among HF patients and (0.019±0.0544 ng/ml) a mong control group (p value 0.004). Th is finding was in accordance with[11, 22-25]. In our study; eGFR was statistically significant lo wer in subjects with HF co mpared to control (80.66± 29.4) vs (157.56±72.1) mL/ min/1.73m2 (P < 0.001). This is in accordance with. This finding is interesting since increased gal-3 is also associated with renal fibrosis (26) and the same process may thus affect both heart and kidneys. Renal dysfunction is one of the most powerful pred ictors of prognosis in HF and plays an impo rtant role in its pathophysiology and the ‘‘overlap’’ may thus also be med iated by gal-3. In our study, the baseline characteristics of all patients, according to quartiles of gal-3 levels showed highly statistically significant increase in gal-3 levels with the decreased LVEF, systolic and diastolic blood pressure (p value <0.001). There was statistically significant increase in gal-3 levels with the increased left ventricular end diastolic diameter "LVEDD" (p value <0.001). The increase in gal-3 levels had no statistically significant relation to age, gender, NYHA functional class, DM, COPD, s moking or use of med ications (ACEI, BB &diuretics). In accordance with our study[8, 20, 28] showed that higher gal-3 levels were associated with other measures of HF severity, including lower systolic blood pressure. Another study showed that patients with LVEDD progression had significant higher levels of gal-3 co mpared to patients showing regression of LVEDD with no significant correlat ion with age, sex, duration of HF or use of anti-failure medicat ions. De Boer et al showed that no-significant relation o f use of anti-failure med ications to plasma gal-3 quartiles. In contrast; reported that gal-3 was not correlated with LVEF. In our study; there were a statistically significant difference between the studied groups as regard SBP, DBP, LVDD, urea (41.9±13.6) vs (16.1±2.8); (P=0.004), uric acid (6.56±2.0) vs (4.07±1.74); (P < 0.001), Hb (11.75±2.18) vs (13.2±1.09); (P= 0.009), Prothro mbin time (13.07±1.45) vs (12.98±0.83) (P= 0.005). In our study; the baseline characteristics of all patients, according to quartiles of gal-3 show that the increase in gal-3 levels had no statistically significant relation to age, gender, NYHA functional class, DM, COPD, s moking or use of med ications (ACEI, BB and diuret ics). In accordance with our study;[8, 22, 31] but Lo k et al showed that gal-3 was correlated with age but no significant correlation with gender, NYHA , functional class, DM, COPD and s moking. On the other hands; another study by Lok et al showed no significant correlation with age, sex, duration of HF or use of anti-failure medicat ions. Felker et al reported a higher gal-3 level that was associated with other measures of HF severity; including lower systolic blood pressure. In accordance with our study; de Boer et al showed no-significant relation of use of anti-failu re 98 Hanan M ahmoud Fayed et al.: Comparative Study of Circulating Cardiac Biomarker Galectin-3 and Troponin I in Heart Failure Patients med ications to gal-3 quartiles in contrast; he reported an increase in quartiles of gal-3 levels has statistically significant relation to age, eGFR, Hb and NYHA functional clas s . In our study; statistically high significant increase in gal-3 levels with the decreased left ventricular ejection fraction (LVEF), systolic and diastolic blood pressure (p value <0.001), and with the increase of both left ventricular end systolic diameter "LVESD" (p value 0.003) & left ventricular end d iastolic diameter " LVEDD" (p value <0.001). In accordance with our study; Lok et al showed that patients with LVEDD progression had significant higher levels of gal-3 co mpared to patients showing regression of LVEDD. In contrast (30, 31) showed that gal-3 was not correlated with LVEF. In our study; receiver-operating characteristic (ROC) analysis for gal-3 shows that the best cut off point which discriminates between disease and normal is gal-3 ≥7.36 with sensitivity 74% and specificity 96.7% and area under the curve (AUC) was 0.876 (p <0.0001) and positive predictive value (PPV) was 94.87% and negative predictive value (NPV) was 68.29%. And ROC analysis for ctn I positivity shows 56% sensitivity & 86.67% specificity and PPV 87.5% and NPV 54.17%. Whereas combined[ctn I positivity + gal-3 at (≥ 7.36 ng/ml)] shows 84% sensitivity & 80 % specificity and PPV 87.5% and NPV 75% i.e. improve gal-3 sensitivity and the negative predicator value so both together are valuable markers in pred icting the HF severity. In accordance with our study; A study by van Kimmenade et al showed that the ROC analysis for gal-3 for the diagnosis of HF showed AUC of 0.72 (p < 0.0001); with an optimal cutoff of 6.88 ng/ml yielding a sensitivity of 80% and a specificity of 52%. Another study by de Boer et al showed AUC was 0.72 (P<0.0001); the optimal cut-off of gal-3 was 6.88 ng/mL wh ich resulted in a reasonable sensitivity of 80% but a poor specificity of 52%. We aimed to correlate the results with some morbid ity cofactors in HF patients such as anemia, hyperuricemia and hypernatremia. our study show statistically significant low Hb levels among HF patients compared to controls with mean Hb level among males (11.62±2.93 vs 14.02±0.84) (P<0.0001) & among females (11.86±2.68 vs 12.52±0.82) (P<0.0001); with the overall incidence of anemia was 21(42%) among HF patients, 52% of them was normochro mic normocytic anemia and 48% of them was hypo-chromic microcytic anemia. In accordance with our study; a study by Groenveld et al showed that 37.2% of patients with CHF were anemic concluding that anemia is associated with an increased risk of mo rtality in both systolic and diastolic CHF& should, therefore, considered as a useful prognosticator and therapeutic strategies aimed to increase hemoglobin levels in CHF . So these patients should be investigated to improve morb idity and potentially mortality in them. Another study by Tehrani et al showed that anemia was present in 55% of the CHF patients. In our study serum uric acid levels show statistically significant high levels among HF patients with mean uric acid level among males (7.24±1.76) and among females (6.43±2.04) co mpared to controls (3.71±1.26 among males) and (4.43±.1.43) among females. In accordance with our study; Ogino et al showed that serum uric acid was significantly increased (p<0.01) in relation to NYHA HF severity (control 5.45± 0.70 mg/dl, NYHA I 6.48± 1.70 mg/dl, NYHA II 7.34±1.94 mg/dl, NYHA III 7.61±2.11 mg/dl, p<0.01) indicating that hyperuricemia was common in CHF, and it is a strong independent marker of prognosis. This may be exp lained by the fact that serum uric acid level is an index of o xidative stress in the human body (36), and was known to contribute to endothelial dysfunction by impairing nitric o xide production . Seru m uric acid has shown to be inversely correlated with the measures of functional capacity and maximal o xygen intake in heart failure patients. Increased oxidative stress results from an imbalance between reactive o xygen species and endogenous antioxidant defense mechanisms. The imbalance can exert profoundly deleterious effects on endothelial function as well as on the pathogenesis and progression of HF. A mong patients with chronic HF, serum uric acid concentrations were associated with greater activity of superoxide dis mutase and endotheliu m dependent vasodilatation. In our study serum sodium showed non-significant elevations among HF patients as all patients were on diuretic therapy. The main limitation of the current study was its relatively small size. Furthermo re, we measured gal-3 on a single time point and thus can only speculate on its importance over time. Limitations of our study include the fact that gal-3 did not correlate with severity of dyspnea as categorized by the NYHA functional classification. Such a lack of correlation makes, according to so me investigators, a new diagnostic serum marker less suitable for clin ical practice. Ho wever, a prognostic marker in HF actually does not necessarily correlate with NYHA functional classificat ion, wh ich was according to some investigators, rather subjective and merely a “crude estimation of a patient’s functional capacity”. Because of these limitations, we regard our study main ly as a hypothesis-generating study. 6. Conclusions Gal-3 is a novel bio marker when used in HF patients help improving prognostication and its comb ined assessment with ctn I help to tailor the most appropriate treatment strategy on a more indiv idualized basis and using gal-3 as therapeutic target in treat ment of chronic HF in future is suggested. In additions; gal-3 assessment with ctn I may allow the identification and treatment of patients with suspected HF e.g. coronary artery disease who display adverse remodeling and, in doing so, prevent the development of HF. 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