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Prognostic Values of Serum Tenascin-C in Patients with Ischaemic Heart Disease and Heart Failure
ORIGINAL ARTICLE
Original Article
Prognostic Values of Serum Tenascin-C in Patients with Ischaemic Heart Disease and Heart Failure Heng-Chen Yao a , Qian-Feng Han a , Ai-Ping Zhao a , Dao-Kuo Yao b and Le-Xin Wang a,c,∗ a
Department of Cardiology, Liaocheng People’s Hospital of Taishan Medical University, Shandong Province 252000, China b Department of Cardiology, Beijing Friendship Hospital of China Capital Medical University, Beijing, China c School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia
Objective: The aim of this study was to evaluate the prognostic values of serum tenascin-C in patients with heart failure and ischaemic heart disease. Methods: Serum tenascin-C levels were assessed in 83 patients with heart failure and in 30 healthy subjects. The correlations between serum tenascin-C levels and left ventricular ejection fraction, serum B-type natriuretic peptide and procollagen III were analysed. Patients were followed up for 12 months, and the relations between the serum levels of tenascin-C and cardiac events (re-hospitalisation for worsening heart failure and mortality) were analysed. Results: Serum tenascin-C levels in patients with heart failure were higher than in healthy volunteers (72.24 ± 11.02 vs. 22.78 ± 2.51 g/L, p < 0.01). Serum tenascin-C levels in patients of NYHA class IV were higher than in patients with NYHA class II (88.56 ± 3.73 vs. 64.88 ± 3.15 g/L, p < 0.01). The levels of tenascin-C were negatively correlated with the left ventricular ejection fraction (r = −0.636, p < 0.01), but were positively correlated with serum B-type natriuretic peptide (r = 0.553, p < 0.01) or procollagen III levels (r = 0.665, p < 0.01). An increased level of tenascin-C was an independent predictor for combined re-hospitalisation and mortality (OR 1.22, 95% CI: 0.86–2.14). Conclusion: Serum tenascin-C levels were elevated in patients with heart failure. The levels of tenascin-C were associated with the severity of left ventricular dysfunction and 12-month major adverse cardiac events. (Heart, Lung and Circulation 2013;22:184–187) © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved. Keywords. Heart failure; Tenascin-C; B-type natriuretic peptide; Procollagen
Introduction
I
schaemic heart disease describes a condition in which coronary artery disease results in severe myocardial dysfunction, which is mainly manifested by significant heart failure [1,2]. The prognosis of heart failure in patients with ischaemic heart disease has improved since the introduction of angiotensin converting enzyme inhibitors/angiotensin receptor blockers and coronary artery intervention therapy. However, heart failure remains a progressive condition with a higher morbidity and mortality. Tenascin-C, an extracellular matrix oligosaccharides protein, plays an important role in the development of the myocardium in early stage embryos, but it is not detected in adults [3]. Tenascin-C can re-express in some pathological conditions, such as athero-thrombosis [4], intimal hyperplasia [5], myocardial infarction [6], cardiomyopathy [7] and coronary valve Received 3 September 2012; accepted 20 October 2012; available online 21 November 2012 ∗
Corresponding author at: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia. Tel.: +61 2 69332905; fax: +61 2 69332587. E-mail address: [email protected] (L.-X. Wang).
calcification [8]. Studies have shown increased serum or plasma concentration of tenascin-C in patients with a range of cardiac problems, including acute myocardial infarction [6], pulmonary artery hypertension [9], and dilated cardiomyopathy [10,11]. Tenascin-C levels were found elevated and were correlated with New York heart association (NYHA) function classes in patients with dilated cardiomyopathy [11]. Increased levels of tenascinC were predictive of major cardiac events in patients with dilated or hypertrophied cardiomyopathy [12,13]. However, the levels of tenascin-C and its relationship with heart function in patients with ischaemic heart disease were unclear, and the prognostic values of tenascin-C in ischaemic cardiomyopathy has not been fully investigated. The aim of this study was to evaluate the changes of tenascin-C levels and the relations with major adverse cardiac events in patients with ischaemic cardiomyopathy and decompensated heart failure.
Materials and Methods Patient Selection Eighty-three consecutive patients with chronic heart failure were enrolled in the study. The diagnosis of heart
© 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2012.10.005
failure was according to the current guideline [14] and ischaemic aetiology of heart failure was confirmed by a history of myocardial infarction or coronary stenosis on coronary angiogram. Patients were eligible if their left ventricular ejection fraction (LVEF) < 45% on transthoracic echocardiography. Patients with infection or inflammatory diseases, autoimmune diseases, liver and kidney dysfunction, malignant cancer, severe trauma, surgical intervention within three months were excluded. Thirty healthy volunteers from people who presented to our hospital’s health clinics for annual health check-ups were enrolled as the control group. Physical examination, ECG, chest X-ray and blood biochemistry studies in these subjects revealed no cardiovascular or other chronic diseases.
Transthoracic Echocardiography Echocardiography was conducted as previously described [15]. Imaging was performed using a HP 5500 system. Patients were imaged in the left lateral decubitus position, and the images of the parasternal and apical views (standard long axis, two- and four-chamber image) were obtained. LVEF was calculated from the conventional apical two- and four-chamber images, using the biplane Simpson’s technique [16]. Echocardiographic examinations were conducted after the heart failure patients’ admission and on the day of venous blood collection from tenascin-C studies. The cardiologist who performed the echocardiographic studies was not aware of patients tenascin-C or other biochemical test results.
Assay of Serum Tenascin-C Levels by ELISA Venous blood samples were obtained and serum samples were centrifuged. Serum aliquoted and stored at −80 until time of assay. The ELISA double antibody sandwich assay was used to determine the serum levels of tenascin-C as previously described [17]. Briefly, 100 l of serum samples were added into plate wells, which were coated and incubated for 2 h at 37 ◦ C. After discarding the liquid and washing, working fluid A (100 l) was added to each well and incubated for 1 h at 37 ◦ C. Working fluid B was then added to each well and incubated for 30 min at 37 ◦ C. The optical density (OD) of each well was measured with a microplate reader at 450 nm wavelength, and the tenascinC content of the sample was calculated.
Biochemical Analysis Serum B-type natriuretic peptide (BNP) was determined using radioimmunoassay. Serum procollagen type three (PC-III) content was measured as previously described by our laboratory [18]. The testing kits for BNP and PC-III were provided by the Jingmei Products Company, Shenzhen, China.
Follow-up Patients were followed-up in our clinics every two months with clinical examination and echocardiography for a total of 12 months. Major adverse cardiac events were defined as re-hospitalisation due to worsening of heart failure and death.
Yao et al. Tenascin-C and heart failure
185
Statistics Analysis Continuous variables were presented as mean ± standard deviation, and were compared by two-tail student t test or one way analysis of variance (ANOVA) for multiple variables. Categorical data were presented as numbers and percentages, and were compared with chi-squire test or Fisher exact test. Cox regression analysis was used to assess the prognostic value of serum tenascin-C on major adverse cardiac events. All data were analysed by SPSS 11.0 software (SPSS, Inc. Chicago, Illinois). A two-sided p value of ≤0.05 was considered to be significant.
Results General Findings A total of 83 patients were included in the study (43 men and 40 women). NYHA function class II was found in 33; class III in 27 and class IV in 23 patients, respectively. Baseline characteristics of the patients in each group are summarised in Table 1. There were no statistically significant differences among the groups of cardiac function class II, III and IV in age, sex, history of hypertension, diabetics and myocardial infarction, and medication use of diuretics, ACE inhibitors, digoxin and statins (all p > 0.05). The mean LVEF in NYHA class IV patients was lower than in NYHA class II or III patients (p < 0.01, Table 1).
Serum BNP, PC III The mean values of serum BNP and PC III in heart failure patients were higher than in the healthy subjects (p < 0.01, Table 2). The mean values of serum BNP and PC III in NYHA IV patients were higher than in the NYHA II patients (p < 0.01, Table 2).
Serum Tenascin-C As shown in Table 2, serum tenascin-C levels in patients with heart failure were higher than in healthy volunteers (p < 0.01). Serum tenascin-C levels in patients of NYHA class IV were higher than in class II (p < 0.01).
Relations Between Serum Tenascin-C and Left Ventricular Function The levels of tenascin-C were negatively correlated with LVEF (r = −0.636, p < 0.01), and were positively correlated with serum BNP levels (r = 0.553, p < 0.01) and PCIII (r = 0.665, p < 0.01).
Prognostic Value of Tenascin-C on Major Adverse Cardiac Events During the 12-month follow-up, major adverse cardiac events were observed in 14 patients (16.9%), including 10 re-hospitalisations as a result of worsening heart failure, and four deaths. After adjustment for age, sex, baseline left ventricular ejection fraction, pharmacological therapies, the baseline tenascin-C levels were predictive of the major adverse cardiac events (OR 1.22, 95% CI: 0.86–2.14). Baseline BNP levels were also predictive of the major adverse cardiac events (OR 1.06, 95% CI: 0.66–1.98).
ORIGINAL ARTICLE
Heart, Lung and Circulation 2013;22:184–187
ORIGINAL ARTICLE
186
Yao et al. Tenascin-C and heart failure
Heart, Lung and Circulation 2013;22:184–187
Table 1. Baseline Characteristics of the Patients. Variables
Heart Failure
Control (n = 30)
p Value
NYHA II (n = 33)
NYHA III (n = 27)
NYHA IV (n = 23)
58.7 ± 7.3
56.2 ± 8.5
60.4 ± 10.1
54.9 ± 7.9
0.075
Male n (%)
18(54.5)
14(51.9)
11(47.8)
15(50.0)
0.965
Hypertension n (%)
10(30.3)
9(33.3)
13(56.5)
7(23.3)
0.076
Diabetics n (%)
8(24.2)
10(37.0)
12(52.2)
6(20.0)
0.057
Prior MI n (%)
3(9.1)
3(11.1)
4(17.4)
0(0)
0.160
Diuretics
14(42.4)
15(55.6)
17(73.9)
0(0)
0.066
ACEI
28(84.8)
24(88.9)
20(87.0)
7(23.3)
<0.01
Beta-blockers
26(78.8)
17(63.0)
9(39.1)
5(16.7)
<0.01
Digoxin
9(27.3)
10(37.5)
13(56.5)
0(0)
0.085
Statins
29(87.9)
25(92.6)
20(89.2)
0(0)
0.501
0.43 ± 0.06
0.37 ± 0.03
0.33 ± 0.03*
0.67 ± 0.06
0.66
Age (yrs)
Medications n (%)
LVEF
Data are expressed as means ± SD. MI, myocardial infarction; ACEI, angiotensin converting enzyme inhibitor; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction. ∗ p < 0.01 vs. NYHA II.
Discussions The main findings of this study were that serum tenascin-C levels were elevated in patients with ischaemic heart disease and heart failure, and the serum levels of tenascin-C were correlated with the levels of LVEF, BNP and PCIII. It was also found that baseline tenascin-C levels were predictive of the major adverse cardiac events in these patients. These findings suggest that serum tenascin-C levels are associated with the severity of heart failure and the prognosis in patients with ischaemic heart disease. As previously reported, tenascin-C is expressed in the myocardial inflammatory regions of myocarditis and acute myocardial infarction [19,20]. In AMI patients, high expression was found in the infarct myocardium, and circulating tenascin-C levels also increased, which suggests the presence of inflammation in infarct area [6]. High serum levels of tenascin-C after AMI reflects remodelling activities which are associated with adverse cardiac events [6]. Tenascin-C expression might reflect cardiac function and the prognosis in heart failure patients. In this study, the levels of serum tenascin-C levels were associated with the severity of heart failure, and the increased levels of baseline tenascin-C were associated with a poor prognosis.
BNP, a ventricular secreted peptide, was widely used to evaluate the degree of heart failure [14,21]. Studies have shown that levels of BNP were related to the degree of heart failure [22]. In this study we found that serum levels of tenascin-C were positively correlated with the levels of BNP, further confirming that that serum tenascin-C might be an alternative indicator for heart failure in patients with heart failure. PC III are released during collagen biosynthesis and used as a biomarker of collagen synthesis [23–25]. Rise of PC III levels were reported in patients with chronic cardiac failure with established left ventricular systolic dysfunction and chronic ischaemia, in which collagen synthesis was the main issue, and associated with its long-term cardiovascular events in heart failure patients [25–27]. The positive correlation of serum tenascin-C levels with PC III in this study suggest that tenascin-C may be an indicator of myocardial fibrosis, but the relations between tenascin-C the long-term clinical outcomes remains unknown. In conclusion, serum tenascin-C levels were elevated in patients with heart failure, and the levels of tenascin-C were correlated with LVEF, BNP and PC III. Furthermore, baseline tenascin-C levels were predictive of 12-month re-hospitalisation for worsening heart failure and mortality. Therefore, serum tenascin-C levels, together with other biomarkers such as BNP, may be used to predict the
Table 2. Biochemical Indices and Ventricular Function in Heart Failure and Control Groups. Indices
Heart Failure Total (n = 83)
NYHA II (n = 33)
NYHA III (n = 27)
Control (n = 30) NYHA IV (n = 23)
72.2 ± 11.0**
64.9 ± 3.1
67.3 ± 5.4
88.6 ± 3.1*
22.8 ± 2.5
BNP (ng/L)
105.8 ± 44.2**
79.9 ± 7.4
100.8 ± 11.5
148.9 ± 63.9*
13.0 ± 6.4
PC III (U/L)
624.3 ±
449.8 ± 86.9
677.6 ± 102.3
Tenascin-C (g/L)
184.9**
812.07*
Data are expressed as means ± SD. NYHA: New York Heart Association; BNP, B-type natriuretic peptide; PC, procollagen. p < 0.01 vs. control and NYHA II. ∗∗ p < 0.01 vs. control. ∗
266.2 ± 82.3
Yao et al. Tenascin-C and heart failure
prognosis of heart failure in patients with ischaemic heart disease.
Conflict of interest No conflict of interest to declare.
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ORIGINAL ARTICLE
Heart, Lung and Circulation 2013;22:184–187
Original Article
Prognostic Values of Serum Tenascin-C in Patients with Ischaemic Heart Disease and Heart Failure Heng-Chen Yao a , Qian-Feng Han a , Ai-Ping Zhao a , Dao-Kuo Yao b and Le-Xin Wang a,c,∗ a
Department of Cardiology, Liaocheng People’s Hospital of Taishan Medical University, Shandong Province 252000, China b Department of Cardiology, Beijing Friendship Hospital of China Capital Medical University, Beijing, China c School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia
Objective: The aim of this study was to evaluate the prognostic values of serum tenascin-C in patients with heart failure and ischaemic heart disease. Methods: Serum tenascin-C levels were assessed in 83 patients with heart failure and in 30 healthy subjects. The correlations between serum tenascin-C levels and left ventricular ejection fraction, serum B-type natriuretic peptide and procollagen III were analysed. Patients were followed up for 12 months, and the relations between the serum levels of tenascin-C and cardiac events (re-hospitalisation for worsening heart failure and mortality) were analysed. Results: Serum tenascin-C levels in patients with heart failure were higher than in healthy volunteers (72.24 ± 11.02 vs. 22.78 ± 2.51 g/L, p < 0.01). Serum tenascin-C levels in patients of NYHA class IV were higher than in patients with NYHA class II (88.56 ± 3.73 vs. 64.88 ± 3.15 g/L, p < 0.01). The levels of tenascin-C were negatively correlated with the left ventricular ejection fraction (r = −0.636, p < 0.01), but were positively correlated with serum B-type natriuretic peptide (r = 0.553, p < 0.01) or procollagen III levels (r = 0.665, p < 0.01). An increased level of tenascin-C was an independent predictor for combined re-hospitalisation and mortality (OR 1.22, 95% CI: 0.86–2.14). Conclusion: Serum tenascin-C levels were elevated in patients with heart failure. The levels of tenascin-C were associated with the severity of left ventricular dysfunction and 12-month major adverse cardiac events. (Heart, Lung and Circulation 2013;22:184–187) © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved. Keywords. Heart failure; Tenascin-C; B-type natriuretic peptide; Procollagen
Introduction
I
schaemic heart disease describes a condition in which coronary artery disease results in severe myocardial dysfunction, which is mainly manifested by significant heart failure [1,2]. The prognosis of heart failure in patients with ischaemic heart disease has improved since the introduction of angiotensin converting enzyme inhibitors/angiotensin receptor blockers and coronary artery intervention therapy. However, heart failure remains a progressive condition with a higher morbidity and mortality. Tenascin-C, an extracellular matrix oligosaccharides protein, plays an important role in the development of the myocardium in early stage embryos, but it is not detected in adults [3]. Tenascin-C can re-express in some pathological conditions, such as athero-thrombosis [4], intimal hyperplasia [5], myocardial infarction [6], cardiomyopathy [7] and coronary valve Received 3 September 2012; accepted 20 October 2012; available online 21 November 2012 ∗
Corresponding author at: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia. Tel.: +61 2 69332905; fax: +61 2 69332587. E-mail address: [email protected] (L.-X. Wang).
calcification [8]. Studies have shown increased serum or plasma concentration of tenascin-C in patients with a range of cardiac problems, including acute myocardial infarction [6], pulmonary artery hypertension [9], and dilated cardiomyopathy [10,11]. Tenascin-C levels were found elevated and were correlated with New York heart association (NYHA) function classes in patients with dilated cardiomyopathy [11]. Increased levels of tenascinC were predictive of major cardiac events in patients with dilated or hypertrophied cardiomyopathy [12,13]. However, the levels of tenascin-C and its relationship with heart function in patients with ischaemic heart disease were unclear, and the prognostic values of tenascin-C in ischaemic cardiomyopathy has not been fully investigated. The aim of this study was to evaluate the changes of tenascin-C levels and the relations with major adverse cardiac events in patients with ischaemic cardiomyopathy and decompensated heart failure.
Materials and Methods Patient Selection Eighty-three consecutive patients with chronic heart failure were enrolled in the study. The diagnosis of heart
© 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2012.10.005
failure was according to the current guideline [14] and ischaemic aetiology of heart failure was confirmed by a history of myocardial infarction or coronary stenosis on coronary angiogram. Patients were eligible if their left ventricular ejection fraction (LVEF) < 45% on transthoracic echocardiography. Patients with infection or inflammatory diseases, autoimmune diseases, liver and kidney dysfunction, malignant cancer, severe trauma, surgical intervention within three months were excluded. Thirty healthy volunteers from people who presented to our hospital’s health clinics for annual health check-ups were enrolled as the control group. Physical examination, ECG, chest X-ray and blood biochemistry studies in these subjects revealed no cardiovascular or other chronic diseases.
Transthoracic Echocardiography Echocardiography was conducted as previously described [15]. Imaging was performed using a HP 5500 system. Patients were imaged in the left lateral decubitus position, and the images of the parasternal and apical views (standard long axis, two- and four-chamber image) were obtained. LVEF was calculated from the conventional apical two- and four-chamber images, using the biplane Simpson’s technique [16]. Echocardiographic examinations were conducted after the heart failure patients’ admission and on the day of venous blood collection from tenascin-C studies. The cardiologist who performed the echocardiographic studies was not aware of patients tenascin-C or other biochemical test results.
Assay of Serum Tenascin-C Levels by ELISA Venous blood samples were obtained and serum samples were centrifuged. Serum aliquoted and stored at −80 until time of assay. The ELISA double antibody sandwich assay was used to determine the serum levels of tenascin-C as previously described [17]. Briefly, 100 l of serum samples were added into plate wells, which were coated and incubated for 2 h at 37 ◦ C. After discarding the liquid and washing, working fluid A (100 l) was added to each well and incubated for 1 h at 37 ◦ C. Working fluid B was then added to each well and incubated for 30 min at 37 ◦ C. The optical density (OD) of each well was measured with a microplate reader at 450 nm wavelength, and the tenascinC content of the sample was calculated.
Biochemical Analysis Serum B-type natriuretic peptide (BNP) was determined using radioimmunoassay. Serum procollagen type three (PC-III) content was measured as previously described by our laboratory [18]. The testing kits for BNP and PC-III were provided by the Jingmei Products Company, Shenzhen, China.
Follow-up Patients were followed-up in our clinics every two months with clinical examination and echocardiography for a total of 12 months. Major adverse cardiac events were defined as re-hospitalisation due to worsening of heart failure and death.
Yao et al. Tenascin-C and heart failure
185
Statistics Analysis Continuous variables were presented as mean ± standard deviation, and were compared by two-tail student t test or one way analysis of variance (ANOVA) for multiple variables. Categorical data were presented as numbers and percentages, and were compared with chi-squire test or Fisher exact test. Cox regression analysis was used to assess the prognostic value of serum tenascin-C on major adverse cardiac events. All data were analysed by SPSS 11.0 software (SPSS, Inc. Chicago, Illinois). A two-sided p value of ≤0.05 was considered to be significant.
Results General Findings A total of 83 patients were included in the study (43 men and 40 women). NYHA function class II was found in 33; class III in 27 and class IV in 23 patients, respectively. Baseline characteristics of the patients in each group are summarised in Table 1. There were no statistically significant differences among the groups of cardiac function class II, III and IV in age, sex, history of hypertension, diabetics and myocardial infarction, and medication use of diuretics, ACE inhibitors, digoxin and statins (all p > 0.05). The mean LVEF in NYHA class IV patients was lower than in NYHA class II or III patients (p < 0.01, Table 1).
Serum BNP, PC III The mean values of serum BNP and PC III in heart failure patients were higher than in the healthy subjects (p < 0.01, Table 2). The mean values of serum BNP and PC III in NYHA IV patients were higher than in the NYHA II patients (p < 0.01, Table 2).
Serum Tenascin-C As shown in Table 2, serum tenascin-C levels in patients with heart failure were higher than in healthy volunteers (p < 0.01). Serum tenascin-C levels in patients of NYHA class IV were higher than in class II (p < 0.01).
Relations Between Serum Tenascin-C and Left Ventricular Function The levels of tenascin-C were negatively correlated with LVEF (r = −0.636, p < 0.01), and were positively correlated with serum BNP levels (r = 0.553, p < 0.01) and PCIII (r = 0.665, p < 0.01).
Prognostic Value of Tenascin-C on Major Adverse Cardiac Events During the 12-month follow-up, major adverse cardiac events were observed in 14 patients (16.9%), including 10 re-hospitalisations as a result of worsening heart failure, and four deaths. After adjustment for age, sex, baseline left ventricular ejection fraction, pharmacological therapies, the baseline tenascin-C levels were predictive of the major adverse cardiac events (OR 1.22, 95% CI: 0.86–2.14). Baseline BNP levels were also predictive of the major adverse cardiac events (OR 1.06, 95% CI: 0.66–1.98).
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Table 1. Baseline Characteristics of the Patients. Variables
Heart Failure
Control (n = 30)
p Value
NYHA II (n = 33)
NYHA III (n = 27)
NYHA IV (n = 23)
58.7 ± 7.3
56.2 ± 8.5
60.4 ± 10.1
54.9 ± 7.9
0.075
Male n (%)
18(54.5)
14(51.9)
11(47.8)
15(50.0)
0.965
Hypertension n (%)
10(30.3)
9(33.3)
13(56.5)
7(23.3)
0.076
Diabetics n (%)
8(24.2)
10(37.0)
12(52.2)
6(20.0)
0.057
Prior MI n (%)
3(9.1)
3(11.1)
4(17.4)
0(0)
0.160
Diuretics
14(42.4)
15(55.6)
17(73.9)
0(0)
0.066
ACEI
28(84.8)
24(88.9)
20(87.0)
7(23.3)
<0.01
Beta-blockers
26(78.8)
17(63.0)
9(39.1)
5(16.7)
<0.01
Digoxin
9(27.3)
10(37.5)
13(56.5)
0(0)
0.085
Statins
29(87.9)
25(92.6)
20(89.2)
0(0)
0.501
0.43 ± 0.06
0.37 ± 0.03
0.33 ± 0.03*
0.67 ± 0.06
0.66
Age (yrs)
Medications n (%)
LVEF
Data are expressed as means ± SD. MI, myocardial infarction; ACEI, angiotensin converting enzyme inhibitor; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction. ∗ p < 0.01 vs. NYHA II.
Discussions The main findings of this study were that serum tenascin-C levels were elevated in patients with ischaemic heart disease and heart failure, and the serum levels of tenascin-C were correlated with the levels of LVEF, BNP and PCIII. It was also found that baseline tenascin-C levels were predictive of the major adverse cardiac events in these patients. These findings suggest that serum tenascin-C levels are associated with the severity of heart failure and the prognosis in patients with ischaemic heart disease. As previously reported, tenascin-C is expressed in the myocardial inflammatory regions of myocarditis and acute myocardial infarction [19,20]. In AMI patients, high expression was found in the infarct myocardium, and circulating tenascin-C levels also increased, which suggests the presence of inflammation in infarct area [6]. High serum levels of tenascin-C after AMI reflects remodelling activities which are associated with adverse cardiac events [6]. Tenascin-C expression might reflect cardiac function and the prognosis in heart failure patients. In this study, the levels of serum tenascin-C levels were associated with the severity of heart failure, and the increased levels of baseline tenascin-C were associated with a poor prognosis.
BNP, a ventricular secreted peptide, was widely used to evaluate the degree of heart failure [14,21]. Studies have shown that levels of BNP were related to the degree of heart failure [22]. In this study we found that serum levels of tenascin-C were positively correlated with the levels of BNP, further confirming that that serum tenascin-C might be an alternative indicator for heart failure in patients with heart failure. PC III are released during collagen biosynthesis and used as a biomarker of collagen synthesis [23–25]. Rise of PC III levels were reported in patients with chronic cardiac failure with established left ventricular systolic dysfunction and chronic ischaemia, in which collagen synthesis was the main issue, and associated with its long-term cardiovascular events in heart failure patients [25–27]. The positive correlation of serum tenascin-C levels with PC III in this study suggest that tenascin-C may be an indicator of myocardial fibrosis, but the relations between tenascin-C the long-term clinical outcomes remains unknown. In conclusion, serum tenascin-C levels were elevated in patients with heart failure, and the levels of tenascin-C were correlated with LVEF, BNP and PC III. Furthermore, baseline tenascin-C levels were predictive of 12-month re-hospitalisation for worsening heart failure and mortality. Therefore, serum tenascin-C levels, together with other biomarkers such as BNP, may be used to predict the
Table 2. Biochemical Indices and Ventricular Function in Heart Failure and Control Groups. Indices
Heart Failure Total (n = 83)
NYHA II (n = 33)
NYHA III (n = 27)
Control (n = 30) NYHA IV (n = 23)
72.2 ± 11.0**
64.9 ± 3.1
67.3 ± 5.4
88.6 ± 3.1*
22.8 ± 2.5
BNP (ng/L)
105.8 ± 44.2**
79.9 ± 7.4
100.8 ± 11.5
148.9 ± 63.9*
13.0 ± 6.4
PC III (U/L)
624.3 ±
449.8 ± 86.9
677.6 ± 102.3
Tenascin-C (g/L)
184.9**
812.07*
Data are expressed as means ± SD. NYHA: New York Heart Association; BNP, B-type natriuretic peptide; PC, procollagen. p < 0.01 vs. control and NYHA II. ∗∗ p < 0.01 vs. control. ∗
266.2 ± 82.3
Yao et al. Tenascin-C and heart failure
prognosis of heart failure in patients with ischaemic heart disease.
Conflict of interest No conflict of interest to declare.
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