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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">ETM</journal-id>
<journal-title-group>
<journal-title>Experimental and Therapeutic Medicine</journal-title>
</journal-title-group>
<issn pub-type="ppub">1792-0981</issn>
<issn pub-type="epub">1792-1015</issn>
<publisher>
<publisher-name>D.A. Spandidos</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3892/etm.2016.3987</article-id>
<article-id pub-id-type="publisher-id">ETM-0-0-3987</article-id>
<article-categories>
<subj-group>
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Effect of ticagrelor on the serum level of hs-CRP, ESM-1 and short-term prognosis of patients with acute STEMI</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>Wei</surname><given-names>Peng</given-names></name>
<xref rid="af1-etm-0-0-3987" ref-type="aff">1</xref>
<xref rid="af2-etm-0-0-3987" ref-type="aff">2</xref></contrib>
<contrib contrib-type="author"><name><surname>Han</surname><given-names>Bing</given-names></name>
<xref rid="af1-etm-0-0-3987" ref-type="aff">1</xref></contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Wen-Jun</given-names></name>
<xref rid="af3-etm-0-0-3987" ref-type="aff">3</xref></contrib>
<contrib contrib-type="author"><name><surname>Bai</surname><given-names>Jie</given-names></name>
<xref rid="af3-etm-0-0-3987" ref-type="aff">3</xref></contrib>
<contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Chun-Ying</given-names></name>
<xref rid="af1-etm-0-0-3987" ref-type="aff">1</xref></contrib>
<contrib contrib-type="author"><name><surname>Qiu</surname><given-names>Chong-Rong</given-names></name>
<xref rid="af4-etm-0-0-3987" ref-type="aff">4</xref></contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Qian</given-names></name>
<xref rid="af1-etm-0-0-3987" ref-type="aff">1</xref></contrib>
<contrib contrib-type="author"><name><surname>Fu</surname><given-names>Qiang</given-names></name>
<xref rid="af1-etm-0-0-3987" ref-type="aff">1</xref>
<xref rid="c1-etm-0-0-3987" ref-type="corresp"/></contrib>
<contrib contrib-type="author"><name><surname>Yang</surname><given-names>Xiang-Jun</given-names></name>
<xref rid="af2-etm-0-0-3987" ref-type="aff">2</xref>
<xref rid="c2-etm-0-0-3987" ref-type="corresp"/></contrib>
</contrib-group>
<aff id="af1-etm-0-0-3987"><label>1</label>Department of Cardiology, Xuzhou Central Hospital, The Affiliated Hospital of Southeast University, Xuzhou, Jiangsu 221009, P.R. China</aff>
<aff id="af2-etm-0-0-3987"><label>2</label>Department of Cardiology, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215006, P.R. China</aff>
<aff id="af3-etm-0-0-3987"><label>3</label>Department of Geriatrics, Changhai Hospital of The Second Military Medical University, Shanghai 200433, P.R. China</aff>
<aff id="af4-etm-0-0-3987"><label>4</label>Department of Cardiology, People&#x0027;s Hospital of Ganzhou, Ganzhou, Jiangxi 341000, P.R. China</aff>
<author-notes>
<corresp id="c1-etm-0-0-3987"><italic>Correspondence to</italic>: Dr Qiang Fu, Department of Cardiology, Xuzhou Central Hospital, The Affiliated Hospital of Southeast University, 199 Jiefang Road, Xuzhou, Jiangsu 221009, P.R. China, E-mail: <email>pennsylwestern@163.com</email></corresp>
<corresp id="c2-etm-0-0-3987">Dr Xiang-Jun Yang, Department of Cardiology, The First Affiliated Hospital, Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China, E-mail: <email>yang_xiangjun@163.com</email></corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>02</month>
<year>2017</year></pub-date>
<pub-date pub-type="epub">
<day>21</day>
<month>12</month>
<year>2016</year></pub-date>
<volume>13</volume>
<issue>2</issue>
<fpage>604</fpage>
<lpage>608</lpage>
<history>
<date date-type="received"><day>22</day><month>08</month><year>2016</year></date>
<date date-type="accepted"><day>14</day><month>11</month><year>2016</year></date>
</history>
<permissions>
<copyright-statement>Copyright: &#x00A9; Wei et al.</copyright-statement>
<copyright-year>2017</copyright-year>
<license license-type="open-access">
<license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution-NonCommercial-NoDerivs License</ext-link>, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.</license-p></license>
</permissions>
<abstract>
<p>The aim of the present study was to observe and investigate the changes in the serum level of high-sensitivity C-reactive protein (hs-CRP), the endothelial cell-specific molecule-1 (ESM-1) and short-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated by ticagrelor. We enrolled 107 patients with acute STEMI who were admitted in the Department of Cardiology for the first time with occurrence of symptoms, and we successfully performed emergency operation of percutaneous coronary intervention. The patients were divided into two groups, 54 patients in the ticagrelor group (treatment group) and 53 patients in the clopidogrel group (control group), according to the administration of ticagrelor or clopidogrel in dual anti-platelet therapy. Then, we observed the changes at the time of admission, at 24 h, and 4th and 7th day after administration and investigated the correlations between them and the effect of ticagrelor on the short-term prognosis of acute STEMI patients. Significant increases of the serum levels of hs-CRP and ESM-1 were seen in patients of the two groups 24 h after administration of drugs with statistically significant differences between the groups (P&#x003C;0.05), and on the 4th and 7th day we found a downward trend with statistically significant differences (P&#x003C;0.05). The level of ESM-1 enhanced the increase of hs-CRP, indicating there was a positive correlation between ESM-1 and hs-CRP (r=0.535, P&#x003C;0.001). A comparison of the occurrence rates of ischemic outcome event, bleeding and overall adverse events between the two groups yielded no statistically significant difference (P&#x003E;0.05). In conclusion, the present study demonstrates that ticagrelor can reduce the prevalence of inflammatory reactions rapidly and stabilize the functions of vascular endothelium to improve the stability of atherosclerosis plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome event without any obvious increase in the risk of bleeding. Thus, ticagrelor should be recommended in clinical practices for the treatment of patients with STEMI.</p>
</abstract>
<kwd-group>
<kwd>ticagrelor</kwd>
<kwd>acute ST-segment elevation myocardial infarction</kwd>
<kwd>percutaneous coronary intervention</kwd>
<kwd>high-sensitivity C-reactive protein</kwd>
<kwd>endothelial cell-specific molecule-1</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>As the most severe type of acute coronary syndrome (ACS), acute ST-segment elevation of myocardial infarction (STEMI), with the characteristics of acute onset, poor prognosis and high mortality (<xref rid="b1-etm-0-0-3987" ref-type="bibr">1</xref>), is caused by the vascular endothelial injury and rupture of inflammatory and unstable plaque resulted by coronary atherosclerosis, which can progress to thrombosis, leading to acute occlusion of culprit vessels to severe myocardial ischemia, even to myocardial necrosis. At present, myocardial ischemia-reperfusion, through reopening the myocardial infarction related arteries by percutaneous coronary intervention (PCI), has become one of the major procedures in the treatment of STEMI (<xref rid="b2-etm-0-0-3987" ref-type="bibr">2</xref>). Particular attention has been shifted to the research on the pathogenesis of STEMI, how to prevent thrombosis, reduce the inflammatory reaction, stabilize the characteristics of plaques and improve the vascular endothelial functions to preserve the survived myocardium.</p>
<p>In this study, the objective was set to observe the serum level changes of high-sensitivity C-reactive protein (hs-CRP), a major inflammatory marker reflecting the stability of plaque, and the endothelial cell-specific molecule-1 (ESM-1), the newly found biological marker reflecting the degree of disturbance of endothelial functions of patients with acute STEMI. Our results confirm the correlation between hs-CRP and ESM-1 and the effect of ticagrelor on the short-term prognosis of acute STEMI patients, which serves as reference for research in effective therapy to alleviate the inflammatory reaction, stabilize the endothelial functions and reduce the prevalence of adverse events of cardiovascular system.</p>
</sec>
<sec sec-type="materials|methods">
<title>Materials and methods</title>
<sec>
<title/>
<sec>
<title>Clinical material</title>
<p>We continuously enrolled 107 patients who were admitted to the Xuzhou Center Hospital (Jiangsu, China) between December 2013 and January 2015 for acute STEMI, accepted the procedure of PCI and met the inclusion criteria. There were 62 males and 45 females aged 30&#x2013;70 years. After obtaining written informed consent, we randomly divided these patients into two groups according to the administration of ticagrelor or clopidogrel during the therapy, 54 patients in the ticagrelor group (treatment group: Load dosage of 180 mg, maintenance dosage of 90 mg/time, twice a day) and 53 patients in the clopidogrel group (control group: Load dosage of 300 mg, maintenance dosage of 75 mg/time, once a day), and performed follow-up by telephone for 30 days after the discharge of the enrolled patients. All the cases corresponded with the definition of acute myocardial infarction of the Third Global Seminar of ESC/ACCF/AHA/WHF and the Diagnostic Criteria of Acute Myocardial Infarction stipulated by the Chinese Society of Cardiology (2010) (<xref rid="b3-etm-0-0-3987" ref-type="bibr">3</xref>,<xref rid="b4-etm-0-0-3987" ref-type="bibr">4</xref>). Exclusion criteria were: i) Patients who would have severe adverse reaction to ticagrelor or were resistant to clopidogrel; ii) patients with a history of myocardial infarction or with other heart diseases and/or severe heart failure (NYHA III or IV); iii) patients who had severe hepatic or renal dysfunction; iv) patients who had history of PCI or coronary artery bypass grafting (CABG) or had accepted other types of surgeries or been injured recently; v) patients with endocrine diseases such as diabetes, and immune system diseases such as acute or chronic infections, digestive tract infections, hematological diseases, malignant tumors, rheumatic disease of connective tissues; vi) patients with severe hypertension without any drug controls, cerebrovascular diseases or peripheral vascular disease; and vii) patients who had any conditions deemed inappropriate by researchers for inclusion in the study.</p>
</sec>
<sec>
<title>Baseline material</title>
<p>The baseline material of patients included the gender, age, body mass index (BMI), risk factors of cardiology [smoking, intake of alcohol, hypertension, family medical history of coronary heart disease, the level of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride], the drugs utilized during the study (administration of low-molecular-weight heparin, IIb/IIIa glycoprotein inhibitors, &#x03B2;-receptor inhibitor, ACEI, statins, CCB, nitrates, PPIs, H2RA), count of platelet, levels of glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine, urea nitrogen, blood glucose under stress and ejection fraction (EF).</p>
</sec>
<sec>
<title>Measurement of hs-CRP</title>
<p>Venous blood (5 ml) was drawn from the elbow of each subject at the time of admission, 24 h after administration of drugs and 5 ml of fasting venous blood was drawn from the same site of patients in the morning of the 4th and 7th day after administration. The supernatant of samples was collected for analysis by BN II Automatic Analyzer of Protein (Siemens AG, Munich, Germany) and measurement of hs-CRP by chemiluminescence with the measurement agent of hs-CRP.</p>
</sec>
<sec>
<title>Measurement of ESM-1</title>
<p>Venous blood (5 ml) was drawn from the elbow of each subject at the time of admission, 24 h after administration of drugs and 5 ml of fasting venous blood was drawn from the same site of patients in the morning of the 4th and 7th day after administration. Samples were required to be in a supine position for &#x2265;20 min without any procedures for anti-coagulation and then immediately placed at 4&#x00B0;C to coagulate for 1 h. Samples were centrifuged at 1,760 &#x00D7; g for 15 min under 4&#x00B0;C, and the serum were drawn into EP tubes and stored at &#x2212;80&#x00B0;C for measurement. The expression level of EMS-1 was measured by ELISA, and the ELISA kits were provided by Shanghai Enzyme-linked Biotechnology Co., Ltd. (Shanghai, China).</p>
</sec>
<sec>
<title>Observation of primary efficacy endpoint</title>
<p>A 30-day follow-up was performed for the patients in the two groups and the items for statistical analysis included the following: i) The occurrence rate of ischemic endpoint events, including cardiac death, acute myocardial infarction, symptoms with the urgent need of performing coronary revascularization, or stroke; and ii) occurrence rate of bleeding events, i.e., identifying the occurrence rate of major safety endpoint events (bleeding) during hospitalization and in 30 days after surgery according to PLATO, including major bleeding events (life-threatening or lethal events), other major bleeding events, secondary bleeding events and slight bleeding events, i.e., other bleeding events that did not need any medical intervention, such as bruise, gingival bleeding, bleeding at the injection site (<xref rid="b5-etm-0-0-3987" ref-type="bibr">5</xref>).</p>
</sec>
<sec>
<title>Statistical analysis</title>
<p>Data analysis was performed using SPSS 22.0 (SPSS, Inc., Chicago, IL, USA). Quantitative data were presented as mean &#x00B1; standard deviation (SD). A normality test was conducted for quantitative data. If the data were correspondent with the normal distribution, an independent t-test was applied in difference analysis of quantitative data of two groups; if not correspondent with normal distribution, the Mann-Whitney rank sum test was utilized for the difference analysis of quantitative data of two groups. Quantitative data were presented as cases or percentage (n/&#x0025;), tested by &#x03C7;<sup>2</sup> test or Fisher&#x0027;s exact test. Difference with P&#x003C;0.05 was considered statistically significant. For correlation analysis among variables, if the distribution of variables were correspondent with bivariate normal distribution, Pearson&#x0027;s product-moment correlation analysis was performed and if not correspondent with bivariate normal distribution or ranked data, Spearman&#x0027;s rank correlation analysis was applied. P&#x003C;0.05 was considered to indicate a statistically significant difference.</p>
</sec>
</sec>
</sec>
<sec sec-type="results">
<title>Results</title>
<sec>
<title/>
<sec>
<title>Comparison of baseline material in the groups</title>
<p>In the two groups, no statistically significant differences (P&#x003E;0.05) were found following a comparison of gender, age, BMI, risk factors of cardiology (smoking, intake of alcohol, hypertension, family medical history of coronary heart disease, the level of total cholesterol, LDL, HDL and triglyceride). The results obtained from different treatments during the study (administration of low-molecular-weight heparin, IIb/IIIa glycoprotein inhibitors, &#x03B2;-receptor inhibitor, ACEI, statins, CCB, nitrates, PPIs, H2RA), count of platelet, levels of GOT, GPT, creatinine, urea nitrogen, blood glucose under stress and EF are presented in <xref rid="tI-etm-0-0-3987" ref-type="table">Table I</xref>.</p>
</sec>
<sec>
<title>Comparison of serum levels of hs-CRP and ESM-1 in the two groups</title>
<p>No statistically significant differences were found in the comparison of serum levels of hs-CRP and ESM-1 between the two groups at the time of admission, but significant increases of serum levels of hs-CRP and ESM-1 were seen in patients of the two groups 24 h after administration of drugs with statistically significant differences between the groups (P&#x003C;0.05), and in the 4th and 7th day we found a downward trend with statistically significant differences (P&#x003C;0.05) (<xref rid="tII-etm-0-0-3987" ref-type="table">Table II</xref> and <xref rid="f1-etm-0-0-3987" ref-type="fig">Figs. 1</xref> and <xref rid="f2-etm-0-0-3987" ref-type="fig">2</xref>).</p>
</sec>
<sec>
<title>Correlation between serum levels of ESM-1 and hs-CRP of patients at the time of admission</title>
<p>To investigate the correlation between serum levels of ESM-1 and hs-CRP, we performed Spearman&#x0027;s bivariate analysis. The level of ESM-1 was enhanced with the increase of inflammatory factors, indicating there was a positive correlation between ESM-1 and hs-CRP (r=0.535, P&#x003C;0.001) (<xref rid="tIII-etm-0-0-3987" ref-type="table">Table III</xref> and <xref rid="f3-etm-0-0-3987" ref-type="fig">Fig. 3</xref>).</p>
</sec>
<sec>
<title>Comparison of major efficacy endpoint events of 30 days in the two groups</title>
<p>In comparison of the occurrence rates of ischemic outcome events, bleeding and overall adverse events between the groups, we found no statistically significant difference (P&#x003E;0.05) (<xref rid="tIV-etm-0-0-3987" ref-type="table">Table IV</xref>).</p>
</sec>
</sec>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>Ticagrelor, one of the newly developed cyclo-pentyl-triazolo-pyrimidines (CPTPs), is an oral preparation of P2Y12 receptor antagonist. Compared with other P2Y12 receptor antagonists such as clopidogrel or prasugrel, ticagrelor could, without metabolic activation, exert its effect immediately after oral administration with a median peak-reaching time of 1.5 h, and combine with the P2Y12 receptor reversibly, resulting in a rapid recovery of platelets after drug withdrawal. Additionally, they affected the migration of inflammatory cells to exert other pharmacological effects through suppression on P2Y12 receptor distributed on the surface of inflammatory cells such as microglial cells, neutrophils, dendritic cells and mononuclear macrophages (<xref rid="b6-etm-0-0-3987" ref-type="bibr">6</xref>,<xref rid="b7-etm-0-0-3987" ref-type="bibr">7</xref>).</p>
<p>As an indicator of inflammation with high sensitivity and specificity, hs-CRP interacted with vascular endothelium cells and other cells to accelerate the process of vascular inflammatory reaction, making the plaques inside the coronary artery more unstable, even rupture, leading to a series of pathological and physiological processes such as leukocyte adhesion, activation and oxidation of platelets and newly developed thrombosis. hs-CRP has served as an independent predictive factor for ACS and is of significance in identification of inflammatory reaction, predicating the stability of plaque and cardiac events (<xref rid="b8-etm-0-0-3987" ref-type="bibr">8</xref>,<xref rid="b9-etm-0-0-3987" ref-type="bibr">9</xref>). In this study, we found that serum level of hs-CRP of treatment group was lower than that of control group ay 24 h, and 4th and 7th day after administration of drugs with statistically significant differences (P&#x003C;0.05), indicating the superiority of ticagrelor to the clopidogrel in suppressing the vascular inflammatory reactions. Anti-platelet drugs effectively restrained the process of atheromatous plaques not only by inhibiting the coagulation of platelet and thrombosis, but also possibly through the improvement in ischemic and oxygen-deficient environment and suppression on the immune inflammatory reactions.</p>
<p>First found and reported in 1996, ESM-1, also known as Endocan, is mainly secreted by endothelial cells (<xref rid="b10-etm-0-0-3987" ref-type="bibr">10</xref>). Research has shown that ESM-1 may be a new biological marker for endocrine function disorder. Lassalle <italic>et al</italic> found that ESM-1 was highly expressed in atheromatous plaques, speculating that the increase in secretion of ESM-1 may promote the migration and proliferation of vascular smooth muscle cells (VSMCs) and that ESM-1 may play a role in the pathology of atherosclerosis (<xref rid="b11-etm-0-0-3987" ref-type="bibr">11</xref>). Kose <italic>et al</italic> (<xref rid="b12-etm-0-0-3987" ref-type="bibr">12</xref>) reported that an increase of ESM-1 expression was seen in the subjects, inferring that ESM-1 may be a new biological marker for endothelial pathology. Furthermore, Tadzic <italic>et al</italic> confirmed that the decrease of ESM-1 could reduce the activation of endothelial cells, thus delaying the progress of atherosclerosis (<xref rid="b13-etm-0-0-3987" ref-type="bibr">13</xref>). In the present study, we found that ticagrelor and clopidogrel alleviated the effect of ESM-1 in varying degrees, and statistically significant differences were found in comparison of ESM-1 in ticagrelor group and clopidogrel group at 24 h, and 4th and 7th day after administration of drugs (P&#x003C;0.05), indicating that ticagrelor could better improve the endothelial functions.</p>
<p>To confirm the role of ESM-1 in the progress of STEMI, we performed a correlation analysis for ESM-1 and hs-CRP, and it was found that the level of ESM-1 enhanced the increase of inflammatory factors, indicating there was a positive correlation between ESM-1 and hs-CRP (r=0.535, P&#x003C;0.001). Thus, ESM-1, the marker of endothelial function disorder, and inflammatory factors such as hs-CRP participated in the cause and progression of coronary heart disease and acute events of coronary artery, in which ESM-1 activated the emission of inflammatory factors such as hs-CRP, and inflammatory factors in turn, promoted the expression of ESM-1. This has rarely been reported in the literature. Thus, future investigations are to examine the correlation between ESM-1 and ACS.</p>
<p>In this study, we found no statistically significant differences (P&#x003E;0.05) in comparison of occurrence rate of ischemic endpoint events in 30 days in two groups, which was consistent with the results in literature (<xref rid="b14-etm-0-0-3987" ref-type="bibr">14</xref>), possibly due to the small number of samples. In addition, there was no statistically significant difference in comparison of occurrence rate of bleeding events (P&#x003E;0.05), suggesting that no significant increase was seen in risk of bleeding events in ticagrelor group compared to the clopidogrel group and ticagrelor is safe and effective for patients.</p>
<p>In conclusion, ticagrelor, in the treatment of patients with STEMI, can decrease the level of inflammatory factors, reduce the prevalence of inflammatory reactions rapidly and stabilize the functions of vascular endothelium to improve the stability of atherosclerosis plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome events without any obvious increase in the risk of bleeding. Thus, ticagrelor should be recommended in clinical practice.</p>
</sec>
</body>
<back>
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</back>
<floats-group>
<fig id="f1-etm-0-0-3987" position="float">
<label>Figure 1.</label>
<caption><p>Comparison of serum level of hs-CRP of patients at different time-points in the groups. <sup>#</sup>Comparison between treatment and control groups (P&#x003C;0.05). hs-CRP, high-sensitivity C-reactive protein.</p></caption>
<graphic xlink:href="etm-13-02-0604-g00.tif"/>
</fig>
<fig id="f2-etm-0-0-3987" position="float">
<label>Figure 2.</label>
<caption><p>Comparison of serum level of ESM-1 of patients at different time-points in the groups. <sup>#</sup>Comparison between treatment and control groups (P&#x003C;0.05). ESM-1, endothelial cell-specific molecule-1.</p></caption>
<graphic xlink:href="etm-13-02-0604-g01.tif"/>
</fig>
<fig id="f3-etm-0-0-3987" position="float">
<label>Figure 3.</label>
<caption><p>Scatter diagram of correlation between serum levels of hs-CRP and ESM-1. hs-CRP, high-sensitivity C-reactive protein; ESM-1, endothelial cell-specific molecule-1.</p></caption>
<graphic xlink:href="etm-13-02-0604-g02.tif"/>
</fig>
<table-wrap id="tI-etm-0-0-3987" position="float">
<label>Table I.</label>
<caption><p>Comparison of baseline material of patients in the two groups.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Variables</th>
<th align="center" valign="bottom">Treatment group (N=54)</th>
<th align="center" valign="bottom">Control group (N=53)</th>
<th align="center" valign="bottom">P-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Gender (male/female)</td>
<td align="center" valign="top">31/23</td>
<td align="center" valign="top">31/22</td>
<td align="center" valign="top">0.910</td>
</tr>
<tr>
<td align="left" valign="top">Age (years)</td>
<td align="center" valign="top">53.28&#x00B1;11.85</td>
<td align="center" valign="top">52.49&#x00B1;11.69</td>
<td align="center" valign="top">0.730</td>
</tr>
<tr>
<td align="left" valign="top">BMI (kg/m<sup>2</sup>)</td>
<td align="center" valign="top">24.80&#x00B1;2.55</td>
<td align="center" valign="top">24.21&#x00B1;2.46</td>
<td align="center" valign="top">0.226</td>
</tr>
<tr>
<td align="left" valign="top">Risk factors of cardiology, n (&#x0025;)</td>
<td/>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Smoking</td>
<td align="center" valign="top">26 (48.1)</td>
<td align="center" valign="top">25 (47.2)</td>
<td align="center" valign="top">0.919</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Intake of alcohol</td>
<td align="center" valign="top">30 (55.6)</td>
<td align="center" valign="top">27 (50.9)</td>
<td align="center" valign="top">0.633</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Hypertension</td>
<td align="center" valign="top">21 (38.9)</td>
<td align="center" valign="top">24 (45.3)</td>
<td align="center" valign="top">0.503</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Family medical history of coronary heart disease</td>
<td align="center" valign="top">5 (9.3)</td>
<td align="center" valign="top">4 (7.5)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">TC (mmol/l)</td>
<td align="center" valign="top">4.88&#x00B1;0.55</td>
<td align="center" valign="top">4.75&#x00B1;0.66</td>
<td align="center" valign="top">0.290</td>
</tr>
<tr>
<td align="left" valign="top">LDL-C (mmol/l)</td>
<td align="center" valign="top">3.09&#x00B1;0.41</td>
<td align="center" valign="top">3.18&#x00B1;0.40</td>
<td align="center" valign="top">0.272</td>
</tr>
<tr>
<td align="left" valign="top">TG (mmol/l)</td>
<td align="center" valign="top">1.35&#x00B1;0.43</td>
<td align="center" valign="top">1.33&#x00B1;0.43</td>
<td align="center" valign="top">0.785</td>
</tr>
<tr>
<td align="left" valign="top">Drugs utilized during the study, n (&#x0025;)</td>
<td/>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Low molecular weight heparin</td>
<td align="center" valign="top">54 (100.0)</td>
<td align="center" valign="top">53 (100.0)</td>
<td align="center" valign="top">&#x2212;</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;IIb/IIIa glycoprotein inhibitors</td>
<td align="center" valign="top">24 (44.4)</td>
<td align="center" valign="top">23 (43.4)</td>
<td align="center" valign="top">0.913</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;&#x03B2;-receptor inhibitor</td>
<td align="center" valign="top">43 (79.6)</td>
<td align="center" valign="top">45 (84.9)</td>
<td align="center" valign="top">0.475</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;ACEI/ARB</td>
<td align="center" valign="top">41 (75.9)</td>
<td align="center" valign="top">40 (75.4)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Statins</td>
<td align="center" valign="top">54 (100.0)</td>
<td align="center" valign="top">53 (100.0)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;CCB</td>
<td align="center" valign="top">18 (33.3)</td>
<td align="center" valign="top">19 (35.8)</td>
<td align="center" valign="top">0.784</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Nitrates</td>
<td align="center" valign="top">47 (87.0)</td>
<td align="center" valign="top">45 (84.9)</td>
<td align="center" valign="top">0.751</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;PPIs</td>
<td align="center" valign="top">28 (51.9)</td>
<td align="center" valign="top">30 (56.6)</td>
<td align="center" valign="top">0.622</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;H2RA</td>
<td align="center" valign="top">13 (24.1)</td>
<td align="center" valign="top">12 (22.6)</td>
<td align="center" valign="top">0.861</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;GOT (&#x00B5;/l)</td>
<td align="center" valign="top">39.39&#x00B1;8.50</td>
<td align="center" valign="top">41.45&#x00B1;6.96</td>
<td align="center" valign="top">0.174</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;GPT (&#x00B5;/l)</td>
<td align="center" valign="top">34.56&#x00B1;5.45</td>
<td align="center" valign="top">35.50&#x00B1;6.76</td>
<td align="center" valign="top">0.433</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Creatinine (&#x00B5;mol/l)</td>
<td align="center" valign="top">88.38&#x00B1;11.09</td>
<td align="center" valign="top">85.11&#x00B1;9.90</td>
<td align="center" valign="top">0.111</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Urea nitrogen (mmol/l)</td>
<td align="center" valign="top">6.88&#x00B1;1.65</td>
<td align="center" valign="top">6.55&#x00B1;1.92</td>
<td align="center" valign="top">0.343</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Blood glucose under</td>
<td align="center" valign="top">7.67&#x00B1;2.30</td>
<td align="center" valign="top">7.99&#x00B1;2.42</td>
<td align="center" valign="top">0.483</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;stress (mmol/l)</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;EF</td>
<td align="center" valign="top">0.50&#x00B1;0.04</td>
<td align="center" valign="top">0.49&#x00B1;0.06</td>
<td align="center" valign="top">0.511</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn1-etm-0-0-3987"><p>No statistically significant differences were found in comparison to baseline material in the groups (P&#x003E;0.05). BMI, body mass index; LDL, low-density lipoprotein; GOT, glutamic oxaloacetic transaminase; GPT, glutamic-pyruvic transaminase; EF, ejection fraction.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tII-etm-0-0-3987" position="float">
<label>Table II.</label>
<caption><p>Comparison of serum levels of hs-CRP and ESM-1 in the groups.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Variables</th>
<th align="center" valign="bottom">Treatment group (N=54)</th>
<th align="center" valign="bottom">Control group (N=53)</th>
<th align="center" valign="bottom">P-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">hs-CRP (mg/l)</td>
<td/>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;At the time of admission</td>
<td align="center" valign="top">7.83&#x00B1;2.84</td>
<td align="center" valign="top">7.91&#x00B1;2.72</td>
<td align="center" valign="top">0.779</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;24 h after administration of drugs</td>
<td align="center" valign="top">26.07&#x00B1;5.34</td>
<td align="center" valign="top">27.89&#x00B1;6.50</td>
<td align="center" valign="top">0.002</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;4th day after administration of drugs</td>
<td align="center" valign="top">12.46&#x00B1;4.00</td>
<td align="center" valign="top">14.81&#x00B1;5.51</td>
<td align="center" valign="top">0.001</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;7th day after administration of drugs</td>
<td align="center" valign="top">6.15&#x00B1;1.67</td>
<td align="center" valign="top">7.03&#x00B1;2.31</td>
<td align="center" valign="top">0.011</td>
</tr>
<tr>
<td align="left" valign="top">ESM-1 (mg/l)</td>
<td/>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;At the time of admission</td>
<td align="center" valign="top">1.13&#x00B1;0.15</td>
<td align="center" valign="top">1.12&#x00B1;0.18</td>
<td align="center" valign="top">0.806</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;24 h after administration of drugs</td>
<td align="center" valign="top">1.20&#x00B1;0.18</td>
<td align="center" valign="top">1.27&#x00B1;0.19</td>
<td align="center" valign="top">0.046</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;4th day after administration of drugs</td>
<td align="center" valign="top">1.13&#x00B1;0.17</td>
<td align="center" valign="top">1.20&#x00B1;0.18</td>
<td align="center" valign="top">0.045</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;7th day after administration of drugs</td>
<td align="center" valign="top">1.05&#x00B1;0.16</td>
<td align="center" valign="top">1.12&#x00B1;0.16</td>
<td align="center" valign="top">0.012</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn2-etm-0-0-3987"><p>hs-CRP, high-sensitivity C-reactive protein; ESM-1, endothelial cell-specific molecule-1.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tIII-etm-0-0-3987" position="float">
<label>Table III.</label>
<caption><p>Analysis of the correlation among hs-CRP and ESM-1.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Variables</th>
<th align="center" valign="bottom">hs-CRP</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">ESM-1</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;r</td>
<td align="center" valign="top">0.535</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;P-value</td>
<td align="center" valign="top">&#x003C;0.001</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn3-etm-0-0-3987"><p>hs-CRP, high-sensitivity C-reactive protein; ESM-1, endothelial cell-specific molecule-1.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tIV-etm-0-0-3987" position="float">
<label>Table IV.</label>
<caption><p>Comparison of major efficacy endpoint events of 30 days in the two groups.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Variables</th>
<th align="center" valign="bottom">Treatment group (N=54)</th>
<th align="center" valign="bottom">Control group (N=53)</th>
<th align="center" valign="bottom">P-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Ischemic endpoint events, n (&#x0025;)</td>
<td align="center" valign="top">1 (1.9)</td>
<td align="center" valign="top">3 (5.7)</td>
<td align="center" valign="top">0.363</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Cardiac death</td>
<td align="center" valign="top">1 (1.9)</td>
<td align="center" valign="top">1 (1.9)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Acute myocardial infarction</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">1 (1.9)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Emergency coronary revascularization</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">&#x2212;</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Stroke</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">1 (1.9)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">Bleeding events, n (&#x0025;)</td>
<td align="center" valign="top">5 (9.3)</td>
<td align="center" valign="top">4 (7.5)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Major bleeding events</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">&#x2212;</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Other major bleeding events</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">&#x2212;</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Secondary bleeding events</td>
<td align="center" valign="top">1 (1.9)</td>
<td align="center" valign="top">1 (1.9)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Slight bleeding events</td>
<td align="center" valign="top">4 (7.4)</td>
<td align="center" valign="top">3 (5.7)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">Total adverse events, n (&#x0025;)</td>
<td align="center" valign="top">6 (11.1)</td>
<td align="center" valign="top">7 (13.2)</td>
<td align="center" valign="top">0.740</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</article>
