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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">zh5p4SGyX74DgPJGVwhFzJc</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2016000300194</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2016005006101</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20160024</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Relationship between GRACE Score and Epicardial Fat Thickness in non-STEMI Patients</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gul</surname>
            <given-names>Ilker</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Zungur</surname>
            <given-names>Mustafa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Aykan</surname>
            <given-names>Ahmet Cagri</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gokdeniz</surname>
            <given-names>Teyyar</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kalaycio&#287;lu</surname>
            <given-names>Ezgi</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Turan</surname>
            <given-names>Turhan</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hatem</surname>
            <given-names>Engin</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Boyaci</surname>
            <given-names>Faruk</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">5</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">&#350;ifa University</institution>
        <institution content-type="orgdiv1">Faculty of Medicine</institution>
        <institution content-type="orgdiv2">Department of Cardiology</institution>
        <addr-line>
          <named-content content-type="city">Izmir</named-content>
        </addr-line>
        <country country="TR">Turkey</country>
        <institution content-type="original">&#350;ifa University Faculty of Medicine - Department of Cardiology, Izmir - Turquia</institution>
        <institution content-type="normalized">Sifa University</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital</institution>
        <institution content-type="orgdiv1">Department of Cardiology</institution>
        <addr-line>
          <named-content content-type="city">Trabzon</named-content>
        </addr-line>
        <country country="TR">Turquia</country>
        <institution content-type="original">Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital - Department of Cardiology, Trabzon - Turquia</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Kafkas University</institution>
        <institution content-type="orgdiv1">Faculty of Medicine</institution>
        <institution content-type="orgdiv2">Department of Cardiology</institution>
        <addr-line>
          <named-content content-type="city">Kars</named-content>
        </addr-line>
        <country country="TR">Turkey</country>
        <institution content-type="original">Kafkas University Faculty of Medicine - Department of Cardiology, Kars - Turquia</institution>
        <institution content-type="normalized">Kafkas University</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Erzurum Region Education and Research Hospital</institution>
        <addr-line>
          <named-content content-type="city">Erzurum</named-content>
        </addr-line>
        <country country="TR">Turquia</country>
        <institution content-type="original">Erzurum Region Education and Research Hospital, Erzurum - Turquia</institution>
      </aff>
      <aff id="aff5">
        <label>5</label>
        <institution content-type="orgname">Samsun Education and Research Hospital</institution>
        <addr-line>
          <named-content content-type="city">Samsun</named-content>
        </addr-line>
        <country country="TR">Turquia</country>
        <institution content-type="original">Samsun Education and Research Hospital, Samsun - Turquia</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Ilker Gul,</bold> Department of Cardiology, Sifa University Faculty of Medicine Bornova Hospital, Postal Code 35040, &#304;zmir - Turkey. E-mail: <email>drilkergul46@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Gul I, Zungur M, Aykan AC, Gokdeniz T, Kalaycio&#287;lu E, Turan T, Boyaci F; Acquisition of data: Gul I, Zungur M, Aykan AC, Turan T, Hatem E; Analysis and interpretation of the data: Gul I, Zungur M, Aykan AC, Kalaycio&#287;lu E, Hatem E, Boyaci F; Statistical analysis: Gul I, Zungur M, Aykan AC, Gokdeniz T, Kalaycio&#287;lu E, Turan T, Hatem E; Writing of the manuscript: Gul I; Critical revision of the manuscript for intellectual content: Gul I, Zungur M, Aykan AC, Gokdeniz T.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>16</day>
        <month>02</month>
        <year>2016</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>3</month>
        <year>2016</year>
      </pub-date>
      <volume>106</volume>
      <issue>3</issue>
      <fpage>194</fpage>
      <lpage>200</lpage>
      <history>
        <date date-type="received">
          <day>20</day>
          <month>06</month>
          <year>2015</year>
        </date>
        <date date-type="rev-recd">
          <day>10</day>
          <month>11</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>11</month>
          <year>2015</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>GRACE risk score (GS) is a scoring system which has a prognostic significance in patients with non-ST segment elevation myocardial infarction (non-STEMI).</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>The present study aimed to determine whether end-systolic or end-diastolic epicardial fat thickness (EFT) is more closely associated with high-risk non-STEMI patients according to the GS.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>We evaluated 207 patients who had non-STEMI beginning from October 2012 to February 2013, and 162 of them were included in the study (115 males, mean age: 66.6 &#177; 12.8 years). End-systolic and end-diastolic EFTs were measured with echocardiographic methods. Patients with high in-hospital GS were categorized as the H-GS group (in hospital GS &gt; 140), while other patients were categorized as the low-to-moderate risk group (LM-GS).</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Systolic and diastolic blood pressures of H-GS patients were lower than those of LM-GS patients, and the average heart rate was higher in this group. End-systolic EFT and end-diastolic EFT were significantly higher in the H-GS group. The echocardiographic assessment of right and left ventricles showed significantly decreased ejection fraction in both ventricles in the H-GS group. The highest correlation was found between GS and end-diastolic EFT (r = 0.438).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>End-systolic and end-diastolic EFTs were found to be increased in the H-GS group. However, end-diastolic EFT and GS had better correlation than end-systolic EFT and GS.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Acute Coronary Syndrome</kwd>
        <kwd>Adipose Tissue</kwd>
        <kwd>Myocardial Infarction</kwd>
        <kwd>Echocardiography</kwd>
        <kwd>Pericardium</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Various scoring systems have been developed for prognostic assessment of patients hospitalized with acute coronary syndromes (ACS). American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines emphasize the prognostic importance of GRACE risk score (GS), and recommend it for routine use. GS can be calculated for the in-hospital period and for the six months following discharge from the hospital. In-hospital GS &gt; 140 is considered as increased risk in terms of mortality rates. Early intervention and revascularization therapies are recommended for these patients.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref>
			</p>
      <p>Visceral adipose tissue is known to have endocrine and metabolic activity functions. Epicardial fat (adipose) tissue is a type of visceral adipose tissue that extends along with the coronary arteries. The importance of epicardial fat thickness (EFT) has been shown by growing amount of supportive data in recent years. Increased EFT is associated with hypertension, insulin resistance and inflammatory processes such as diabetes mellitus and metabolic syndrome.<xref ref-type="bibr" rid="B3">3</xref><sup>-</sup><xref ref-type="bibr" rid="B5">5</xref> As a result of the studies investigating the relationship between EFT and coronary artery disease (CAD), EFT was associated with severity and burden of CAD.<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <p>EFT can be measured by means of magnetic resonance imaging (MRI) and multi-detector computed tomography (CT). However, these tests are quite expensive and not for routine use. Echocardiography is quite inexpensive, readily available and easy to perform compared to CT and MRI. For these reasons, the majority of previous studies have calculated EFT using echocardiographic methods. There is no consensus on during which phase of the cardiac cycle EFT should be measured. Although some studies in the literature suggest using end-systolic EFT measurements,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> a greater number of studies recommend end-diastolic EFT measurements.<xref ref-type="bibr" rid="B5">5</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref>
			</p>
      <p>The present study aimed to determine whether end-systolic or end-diastolic EFT is more closely associated with high-risk non-ST segment elevation myocardial infarction (non-STEMI) patients according to the GS.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>This prospective observational cohort study was carried out between October 2012 and February 2013. Patients who had non-STEMI for the first time were included in the study. Patients with chronic lung disease, chronic liver disease, inflammatory rheumatic disease, muscle disease, heart failure, chronic renal failure (creatinine &gt; 2.5 mg/dL), myocarditis, and cardiomyopathic disease were excluded from the study.</p>
      <p>Non-STEMI was diagnosed in the presence of an accelerating pattern of or prolonged angina or recurrent episodes of angina either at rest or during minimal exertion within the last 48-72 hours and levels of troponin or creatine kinase-MB (CK-MB) above the upper limit of normal range. Biochemical parameters were evaluated in blood samples collected during hospitalization. Peak cTnI and CK-MB levels were identified during the cardiac enzyme follow-up.</p>
      <p>The GS was calculated by means of a computer program (<ext-link ext-link-type="uri" xlink:href="http://www.outcomes-umassmed.org/grace/acs_risk">www.outcomes-umassmed.org/grace/acs_risk</ext-link>). Age, systolic blood pressure, serum creatinine level, and Killip class were determined for GS. Cardiac arrest on admission, ST-segment changes, the method of revascularization and data about the increase in cardiac enzymes were entered into the computer program as appropriate. After GS values were calculated, the patients were divided into groups as recommended by the AHA and ESC guidelines on non-STEMI.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref>
			</p>
      <p>Patients with low-to-moderate in-hospital GS (&lt; 140) were categorized as the low-to-moderate GRACE score (LM-GS) group (n = 70) while the patients with high in-hospital GS (&gt; 140) were categorized as the high GRACE score (H-GS) group (n = 92).</p>
      <p>Baseline clinical [heart rate, blood pressure, electrocardiography, laboratory biochemical parameters, angiography], echocardiographic and demographic [age, gender, height, weight] variables of the patients were recorded. The predictor (grouping) variable was the GS, and the primary outcome variable was EFT.</p>
      <sec>
        <title>Echocardiography</title>
        <p>Echocardiographic analysis was performed in left lateral decubitus position according to the American Society of Echocardiography guidelines, within the first 24 hours in intensive care unit using the Vivid S5 cardiovascular ultrasound system (General Electric Vingmed Ultrasound, Horten, Norway). Epicardial fat was defined as an echo-free space between the outer wall of the myocardium and the visceral layer of the pericardium. The largest diameter of epicardial fat located on the right ventricular (RV) free wall was determined. EFT was measured in the parasternal long axis view at end-systole and end-diastole in three cardiac cycles. The average of three cardiac cycles was used for statistical analysis.</p>
        <p>Left ventricular ejection fraction (LVEF) was determined using the Modified Simpson method. For a better evaluation of the RV functions, tricuspid annular plane systolic excursion (TAPSE) amount was calculated from the lateral tricuspid annulus.<xref ref-type="bibr" rid="B13">13</xref> The right ventricular ejection fraction (RVEF) was calculated with 3D echocardiography using the disk summation method. The myocardial performance index, also known as Tei index, is a global estimate of both RV functions. Tei index is a Doppler-derived time interval index that combines both systolic and diastolic cardiac performance. The Tei index is easily derived using conventional pulsed Doppler echocardiography, as previously described by Tei et al.<xref ref-type="bibr" rid="B14">14</xref>
				</p>
        <p>The present study has been designed and conducted in accordance with the Declaration of Helsinki, and the protocol has been approved by the Ethics Committee.</p>
      </sec>
      <sec>
        <title>Variability analysis</title>
        <p>Intra- and inter-observer variability were assessed for the echocardiographic data obtained from a subgroup of 40 subjects. One day later, the first operator repeated the analysis to assess intra-observer variability. To assess inter-observer variability, the second operator who was blinded to the previous measurements analyzed each parameter two days later. Agreement analysis for inter- and intra-observer variability of EFT measurements revealed a high level of agreement with a mean difference of 0.26 (95% limit of agreement: -0.5 to 0.93) and an intraclass correlation coefficient of 0.918 (95% CI 0.830-0.960).</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>Categorical data are presented as frequencies (percentages). Continuous variables are presented as mean &#177; SD. Kolmogorov-Smirnov test was used to assess whether patients' data fit normal distribution. As the data exhibited normal distribution, the independent-samples t-test was used for statistical analysis. Chi-square analysis was performed for categorical variables. Intraclass correlation coefficients and Bland-Altman analysis were used for echocardiographic measurements to assess intra- and inter-observer reproducibility, respectively. Pearson's test was used to analyze the correlation between GS and EFT. Receiver operating characteristic (ROC) analysis was performed to determine whether EFT could predict high-risk groups based on GS scores. A two-tailed p &lt; 0.05 was considered statistically significant.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Baseline demographics and characteristics</title>
        <p>We evaluated 207 patients admitted to our center with non-STEMI, and 45 of them were excluded from the study (chronic lung disease, 22 patients; chronic liver disease, 2 patients; previous heart failure, 10 patients; chronic renal failure, 8 patients; myocarditis, 2 patients; and cardiomyopathic disease, 1 patient). Totally 162 patients were included in the study and 115 of them were male, and the average age was 63.9 &#177; 12.8 years. According to in-hospital GS, 70 patients were categorized as the LM-GS group, and 92 patients were categorized as the H-GS group. The mean age was higher in the H-GS group (73.7 &#177; 10.5 vs. 57.2 &#177; 9.1 years, p &lt; 0.001). Mean systolic blood pressure (147.3 &#177; 27.7 vs. 130.3 &#177; 31.1 mmHg, p &lt; 0.001) and mean diastolic blood pressure (85.5 &#177; 16.1 vs. 78.1 &#177; 19.5 mmHg, p = 0.010) values were higher in the LM-GS group. There was no difference between the groups in terms of body mass index, smoking, and the number of patients with hypertension, and diabetes mellitus. Mortality rate [3 (4.3%) vs. 13 (14.1%), p = 0.037], length of stay in intensive care unit [3.3 &#177; 1.2 days vs. 4.3 &#177; 2.9 days, p = 0.019] and total length of hospital stay [5.6 &#177; 2.5 days vs. 6.9 &#177; 3.8 days, p = 0.020] were significantly higher in the H-GS group compared to the LM-GS group (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>General characteristics of patients with non-ST-elevatlon myocardial Infarction according to the in-hospital GRACE score</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th>
								</th>
                <th align="center">
                  <bold>Low-to-moderate risk group (n = 70)</bold>
                </th>
                <th align="center">
                  <bold>High risk group (n = 92)</bold>
                </th>
                <th align="center">
                  <bold>p value</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Age, years</td>
                <td align="center">57.2 &#177; 9.1</td>
                <td align="center">73.7 &#177; 10.5</td>
                <td align="center">p &lt; 0.001</td>
              </tr>
              <tr>
                <td>Gender, male/female</td>
                <td align="center">56/14</td>
                <td align="center">59/33</td>
                <td align="center">p = 0.027</td>
              </tr>
              <tr>
                <td>Systolic Blood Pressure, mmHg</td>
                <td align="center">147.3 &#177; 27.7</td>
                <td align="center">130.3 &#177; 31.1</td>
                <td align="center">p &lt; 0.001</td>
              </tr>
              <tr>
                <td>Diastolic Blood Pressure, mmHg</td>
                <td align="center">85.5 &#177; 16.1</td>
                <td align="center">78.1 &#177; 19.5</td>
                <td align="center">p = 0.010</td>
              </tr>
              <tr>
                <td>Body Mass Index, kg/m<sup>2</sup></td>
                <td align="center">28.5 &#177; 4.4</td>
                <td align="center">26.7 &#177; 3.7</td>
                <td align="center">p = 0.060</td>
              </tr>
              <tr>
                <td>Smoking, n (%)</td>
                <td align="center">35 (50%)</td>
                <td align="center">50 (54.1%)</td>
                <td align="center">p = 0.583</td>
              </tr>
              <tr>
                <td>Hypertension, n (%)</td>
                <td align="center">40 (57.1%)</td>
                <td align="center">44 (47.8%)</td>
                <td align="center">p = 0.299</td>
              </tr>
              <tr>
                <td>Diabetes mellitus, n (%)</td>
                <td align="center">21 (30.0%)</td>
                <td align="center">33 (35.9%)</td>
                <td align="center">p = 0.376</td>
              </tr>
              <tr>
                <td>Blood Glucose on admission, mg/dL</td>
                <td align="center">139.6 &#177; 60.3</td>
                <td align="center">146.5 &#177; 70.3</td>
                <td align="center">p = 0.515</td>
              </tr>
              <tr>
                <td>Total Cholesterol, mg/dL</td>
                <td align="center">185.7 &#177; 44.9</td>
                <td align="center">204.2 &#177; 55.9</td>
                <td align="center">p = 0.022</td>
              </tr>
              <tr>
                <td>LDL Cholesterol, mg/dL</td>
                <td align="center">133.1 &#177; 37.9</td>
                <td align="center">148.5 &#177; 43.9</td>
                <td align="center">p = 0.019</td>
              </tr>
              <tr>
                <td>HDL Cholesterol, mg/dL</td>
                <td align="center">40.9 &#177; 15.9</td>
                <td align="center">39.9 &#177; 9.8</td>
                <td align="center">p = 0.627</td>
              </tr>
              <tr>
                <td>Triglycerides, mg/dL</td>
                <td align="center">124.8 &#177; 71.4</td>
                <td align="center">131.3 &#177; 96.8</td>
                <td align="center">p = 0.641</td>
              </tr>
              <tr>
                <td>C-Reactive Protein, mg/dL</td>
                <td align="center">1.63 &#177; 3.4</td>
                <td align="center">2.68 &#177; 4.38</td>
                <td align="center">p = 0.013</td>
              </tr>
              <tr>
                <td>Creatinine, mg/dL</td>
                <td align="center">0.84 &#177; 0.2</td>
                <td align="center">1.18 &#177; 0.57</td>
                <td align="center">p &lt; 0.001</td>
              </tr>
              <tr>
                <td>Troponin-I, ng/mL</td>
                <td align="center">31.6 &#177; 30.0</td>
                <td align="center">31.1 &#177; 28.1</td>
                <td align="center">p = 0.951</td>
              </tr>
              <tr>
                <td>LV Ejection Fraction, %</td>
                <td align="center">47.8 &#177; 10.2</td>
                <td align="center">43.3 &#177; 10.5</td>
                <td align="center">p = 0.008</td>
              </tr>
              <tr>
                <td>Interventricular septum, mm</td>
                <td align="center">10.1 &#177; 1.2</td>
                <td align="center">10.1 &#177; 1.36</td>
                <td align="center">p = 0.726</td>
              </tr>
              <tr>
                <td>Posterior Wall, mm</td>
                <td align="center">9.8 &#177; 1.12</td>
                <td align="center">9.9 &#177; 1.26</td>
                <td align="center">p = 0.761</td>
              </tr>
              <tr>
                <td>LV Mass, g</td>
                <td align="center">181.5 &#177; 44.2</td>
                <td align="center">198.7 &#177; 49.3</td>
                <td align="center">p = 0.019</td>
              </tr>
              <tr>
                <td>LV Mass Index, g/m<sup>2</sup></td>
                <td align="center">94.3 &#177; 22.4</td>
                <td align="center">109.4 &#177; 28.4</td>
                <td align="center">p = 0.002</td>
              </tr>
              <tr>
                <td>Epicardial fat thickness (systole), cm</td>
                <td align="center">0.72 &#177; 0.17</td>
                <td align="center">0.81 &#177; 0.12</td>
                <td align="center">p &lt; 0.001</td>
              </tr>
              <tr>
                <td>Epicardial fat thickness (diastole), cm</td>
                <td align="center">0.46 &#177; 0.13</td>
                <td align="center">0.54 &#177; 0.10</td>
                <td align="center">p &lt; 0.001</td>
              </tr>
              <tr>
                <td>SPAP, mmHg</td>
                <td align="center">25.1 &#177; 7.5</td>
                <td align="center">30.7 &#177; 8.7</td>
                <td align="center">p &lt; 0.001</td>
              </tr>
              <tr>
                <td>TAPSE, mm</td>
                <td align="center">20.9 &#177; 4.1</td>
                <td align="center">19.4 &#177; 3.6</td>
                <td align="center">p = 0.017</td>
              </tr>
              <tr>
                <td>RV Ejection Fraction, %</td>
                <td align="center">53.1 &#177; 5.3</td>
                <td align="center">50.1 &#177; 5.4</td>
                <td align="center">p = 0.001</td>
              </tr>
              <tr>
                <td>Tei Index</td>
                <td align="center">0.35 &#177; 0.09</td>
                <td align="center">0.44 &#177; 0.11</td>
                <td align="center">p &lt; 0.001</td>
              </tr>
              <tr>
                <td>SYNTAX score</td>
                <td align="center">20.6 &#177; 10.1</td>
                <td align="center">21.2 &#177; 9.9</td>
                <td align="center">p = 0.625</td>
              </tr>
              <tr>
                <td>LAD lesion, n (%)</td>
                <td align="center">29 (41.4%)</td>
                <td align="center">35 (38.0%)</td>
                <td align="center">p = 0.744</td>
              </tr>
              <tr>
                <td>Cx lesion, n (%)</td>
                <td align="center">17 (24.3%)</td>
                <td align="center">16 (17.4%)</td>
                <td align="center">p = 0.280</td>
              </tr>
              <tr>
                <td>RCA lesion, n (%)</td>
                <td align="center">24 (34.3%)</td>
                <td align="center">41 (44.6%)</td>
                <td align="center">p = 0.149</td>
              </tr>
              <tr>
                <td>Mortality, n (%)</td>
                <td align="center">3 (4.3%)</td>
                <td align="center">13 (14.1%)</td>
                <td align="center">p = 0.037</td>
              </tr>
              <tr>
                <td>Duration in intensive care unit, days</td>
                <td align="center">3.3 &#177; 1.2</td>
                <td align="center">4.3 &#177; 2.9</td>
                <td align="center">p = 0.019</td>
              </tr>
              <tr>
                <td>Total length of hospital stay, days</td>
                <td align="center">5.6 &#177; 2.5</td>
                <td align="center">6.9 &#177; 3.8</td>
                <td align="center">p = 0.020</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>Data are presented as mean&#177;SD or number (percentage)</p>
              <p>*Chi-square and independent sample t-test</p>
              <p>LV: Left ventricular; RV: right ventricular; Cx: circumflex artery; HDL: high density lipoprotein; LAD: left anterior descending artery; LDL: low-density lipoprotein; RCA: right coronary artery; SPAP: systolic pulmonary artery pressure; TAPSE: tricuspid annular plane systolic excursion.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Laboratory findings</title>
        <p>Evaluation of the laboratory data revealed no difference between the average values of postprandial blood glucose, HDL-cholesterol, triglycerides, and cTn-I levels. The mean values of total cholesterol (204.2 &#177; 55.9 vs. 185.7 &#177; 44.9 mg/dL, p = 0.022), LDL-cholesterol (148.5&#177;43.9 vs. 133.1 &#177; 37.9 mg/dL, p = 0.019), C-reactive protein (2.68 &#177; 4.38 vs. 1.63 &#177; 3.4 mg/L, p = 0.013) and creatinine (1.18 &#177; 0.57 vs. 0.84 &#177; 0.20 mg/dL, p &lt; 0.001) were higher in the H-GS group compared to the LM-GS group (<xref ref-type="table" rid="t1">Table 1</xref>). </p>
      </sec>
      <sec>
        <title>Echocardiography and coronary angiography</title>
        <p>There was no difference between the groups regarding interventricular septum and posterior wall thickness. EF was lower in the H-GS group (43.3% &#177; 10.5 vs. 47.8% &#177; 10.2, p = 0.008). End-systolic EFT (0.81 &#177; 0.12 vs. 0.72 &#177; 0.17 cm, p &lt; 0.001), end-diastolic EFT (0.54 &#177; 0.10 vs. 0.46 &#177; 0.13 cm, p &lt; 0.001) and systolic pulmonary artery pressure (SPAP) (30.7 &#177; 8.7 vs. 25.1 &#177; 7.5 mmHg, p &lt; 0.001) were higher in the H-GS group. RVEF, one of the indicators of RV systolic function (50.1% &#177; 5.4 vs. 53.1% &#177; 5.3, p = 0.001) and TAPSE (19.4 &#177; 3.6 vs. 20.9 &#177; 4.1, p = 0.017) were lower in the H-GS group than in the LM-GS group (<xref ref-type="table" rid="t1">Table 1</xref>). Tei index was significantly higher in the H-GS group (0.48 &#177; 0.09 vs. 0.39 &#177; 0.08, p &lt; 0.001).</p>
        <p>Evaluation of the patients' angiograms showed no significant difference between left anterior descending (LAD), circumflex (Cx) and right coronary artery (RCA) involvements (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
      </sec>
      <sec>
        <title>Correlation and ROC analysis</title>
        <p>Based on in-hospital GS, the ROC analysis was performed to calculate the EFT for prediction of patients with high-risk. The end-systolic EFT cut-off value which predicts the H-GS group was calculated as 0.765 cm (AUC: 0.699; 95% CI: 0.613-0.785; sensitivity, 67%; specificity, 64%), and the end-diastolic EFT cut-off value was found to be 0.468 cm for the H-GS group (AUC: 0.709; 95% CI: 0.621-0.797; sensitivity, 68%; specificity, 72%) (<xref ref-type="table" rid="t2">Table 2</xref>, <xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>According to in-hospital GRACE scores (GS), the receiver operating characteristic (ROC) analysis was performed to calculate the epicardial fat thickness (EFT) for the prediction of patients at high risk</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th>
								</th>
                <th align="center">
                  <bold>Cut-off (cm)</bold>
                </th>
                <th align="center">
                  <bold>Sensitivity</bold>
                </th>
                <th align="center">
                  <bold>Specificity</bold>
                </th>
                <th align="center">
                  <bold>AUC</bold>
                </th>
                <th align="center">
                  <bold>95% Confidence Interval</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>EFT end-systole / GS</td>
                <td align="center">0.765</td>
                <td align="center">67%</td>
                <td align="center">64%</td>
                <td align="center">0.699</td>
                <td align="center">0.613-0.785</td>
              </tr>
              <tr>
                <td>EFT end-diastole / GS</td>
                <td align="center">0.468</td>
                <td align="center">68%</td>
                <td align="center">72%</td>
                <td align="center">0.709</td>
                <td align="center">0.621-0.797</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>Receiver operating characteristic (ROC) analysis</p>
              <p>AUC: area under the curve.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>
          <fig id="f1">
            <label>Figure 1</label>
            <caption>
              <title>Receiver operating characteristic (ROC) curve.The end-systolic epicardial fat thickness cut-off value which predicts the H-GS group was calculated as 0.765 cm (AUC: 0.699; 95% CI: 0.613-0.785; sensitivity: 67%; specificity: 64%). End-diastolic epicardial fat thickness cut-off value was found to be 0.468 cm for the H-GS group (AUC: 0.709; 95% CI: 0.621-0.797; sensitivity: 68%; specificity: 72%). (AUC: Area Under the Curve; CI: Confidence Interval; H-GS: High GRACE score).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-106-03-0194-60024-gf01.jpg"/></fig>
        </p>
        <p>The correlation coefficient (r) of in-hospital GS and end-systolic EFT was found as 0.387, while the correlation coefficient (r) of in-hospital GS and end-diastolic EFT was found as 0.438 (<xref ref-type="table" rid="t3">Table 3</xref>).</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Correlation table for the in-hospital GRACE score (GS), SYNTAX score and epicardial fat thickness (EFT) measurements</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th>
								</th>
                <th align="center">
                  <bold>Correlation coefficient (r)</bold>
                </th>
                <th align="center">
                  <bold>p value</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>End-systolic EFT - GS</td>
                <td align="center">r = 0.387</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td>End-diastolic EFT - GS</td>
                <td align="center">r = 0.438</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td>End-systolic EFT - SYNTAX score</td>
                <td align="center">r = 0.285</td>
                <td align="center">0.009</td>
              </tr>
              <tr>
                <td>End-diastolic EFT - SYNTAX score</td>
                <td align="center">r = 0.292</td>
                <td align="center">0.002</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p>Pearson&#8217;s correlation analysis</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>In this study, we aimed to show the relationship between the GS and EFT in patients admitted to our center with a diagnosis of non-STEMI. Our study demonstrated that EFT is associated with increased GS, and statistical analysis suggests that it would be more convenient to measure EFT at the end of diastole.</p>
      <p>GRACE scoring system was initially used for the purpose of following a prognostic assessment of patients with ACS after the multinational Global Registry of Acute Coronary Events (GRACE) study.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B15">16</xref> Detection of a high GS calculated with the help of variables is associated with poor prognosis. Currently, the ACS guidelines recommend its use for risk evaluation. The AHA and ESC ACS diagnosis and treatment guidelines provide suggestions on how to interpret GS. According to these recommendations, in-hospital GS &gt; 140 is an indicator of high morbidity and mortality. These guidelines recommend early revascularization for patients at high risk.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref> In our study, a higher mortality rate was found (p = 0.001) in the H-GS group with GS &gt; 140. Apart from mortality rates, echocardiographic parameters decreased in the H-GS group. The LVEF values of the H-GS group were lower than those of the LM-GS group. The RVEF and TAPSE, which are markers of RV systolic functions, were decreased in the H-GS group. The Tei index and SPAP were increased in the H-GS group.</p>
      <p>Epicardial fat is a type of visceral adipose tissue that extends along coronary arteries in atrioventricular and interventricular grooves. Myocardium and epicardial fat tissue are in direct contact, and the blood supply for these tissues is provided by the same coronary system.<xref ref-type="bibr" rid="B17">17</xref> Therefore, acting as an endocrine organ, epicardial fat tissue can directly and indirectly affect coronary arteries and cardiac structures. Epicardial fat tissue can produce several cytokines that stimulate angiogenesis, inflammation, oxidative stress and atherosclerosis. A number of recent clinical studies have been conducted to investigate the relationship between EFT and cardiovascular diseases. As a result of these studies, increased EFT has been associated with an increased risk of cardiovascular disease.<xref ref-type="bibr" rid="B5">5</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref><sup>-</sup><xref ref-type="bibr" rid="B22">22</xref> EFT is increased in patients with inflammation, advanced age, obesity, hypercholesterolemia, hypertension, atrial fibrillation, diabetes mellitus and metabolic syndrome.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B23">23</xref><sup>-</sup><xref ref-type="bibr" rid="B27">27</xref> In our study, there was no significant difference between the groups in terms of blood glucose and body mass index. The number of patients diagnosed with metabolic syndrome, diabetes and hypertension was similar between groups (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
      <p>There are several recommendations on how to measure EFT. The RV free wall is preferred as the measurement site, and measurements for the calculation of EFT are generally performed at the end of diastole.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref> However, some publications suggest that EFT can also be measured at the end of systole.<sup>(7,11,12 )</sup>It is recommended that EFT should be measured at the end of systole during the cardiac cycle as it is compressed during diastole. In the present study, average EFT values were obtained by employing at least three different measurements for end of systole and end of diastole, and the average EFT values were higher in the H-GS group compared to the LM-GS group (p &lt; 0.001) (<xref ref-type="table" rid="t1">Table 1</xref>). A correlation was observed between in-hospital GS and EFT (in-hospital GS and end-systolic EFT, r = 0.387; end-diastolic, r = 0.438). Evaluation of ROC analyses demonstrated that end-diastolic EFT provided a better prediction of high GS compared to end-systolic EFT (<xref ref-type="table" rid="t2">Table 2</xref>, <xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
      <p>The main limitation of the present study is the relatively small sample size. Secondly, echocardiography is less accurate than other radiological techniques for evaluating epicardial adipose tissue, although a good correlation with MRI has been reported. Moreover, a moderate correlation has been reported with the epicardial fat volume assessed with cardiovascular MRI. Despite the low level of accuracy, echocardiographic measurement of EFT offers greater feasibility compared to MRI.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusions</title>
      <p>Previous studies have shown increased EFT in various conditions and pathologies that may impair cardiac functions. In our study mortality and morbidity rates were increased in H-GS group. The GS showed a positive correlation with end-systolic EFT and end-diastolic EFT. Statistical evaluations demonstrated a better correlation between GS and end-diastolic EFT rather than end-systolic EFT.</p>
      <p>In conclusion, calculating the end-diastolic EFT may provide useful information in patients with high GS during the echocardiographic evaluation of non-STEMI.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1 Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE, et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2012 ACCF/AHA Focused Update of the Guideline or the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Diretrizes 2012 Writing Committee Members. Circulation.2012;126(7):875-910.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Jneid</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Anderson</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Wright</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Adams</surname>
              <given-names>CD</given-names>
            </name>
            <name>
              <surname>Bridges</surname>
              <given-names>CR</given-names>
            </name>
            <name>
              <surname>Casey</surname>
              <given-names>DE</given-names>
            </name>
            <etal/>
            <collab>American College of Cardiology Foundation</collab>
            <collab>American Heart Association Task Force on Practice Guidelines</collab>
          </person-group>
          <article-title>2012 ACCF/AHA Focused Update of the Guideline or the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Diretrizes 2012 Writing Committee Members</article-title>
          <source>Circulation</source>
          <year>2012</year>
          <volume>126</volume>
          <issue>7</issue>
          <fpage>875</fpage>
          <lpage>910</lpage>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2 Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al; ESC Committee for Practice Guidelines. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(23):2999-3054.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hamm</surname>
              <given-names>CW</given-names>
            </name>
            <name>
              <surname>Bassand</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Agewall</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Bax</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Boersma</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Bueno</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
            <collab>ESC Committee for Practice Guidelines</collab>
          </person-group>
          <article-title>ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)</article-title>
          <source>Eur Heart J</source>
          <year>2011</year>
          <volume>32</volume>
          <issue>23</issue>
          <fpage>2999</fpage>
          <lpage>3054</lpage>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3 Teijeira-Fernandez E, Eiras S, Shamagian LG, Shamagian LG, Somoza AS, Delgado C, et al. Lower epicardial adipose tissue adiponectin in patients with metabolic syndrome.Cytokine. 2011;54(2):185-90.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Teijeira-Fernandez</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Eiras</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Shamagian</surname>
              <given-names>LG</given-names>
            </name>
            <name>
              <surname>Shamagian</surname>
              <given-names>LG</given-names>
            </name>
            <name>
              <surname>Somoza</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>Delgado</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Lower epicardial adipose tissue adiponectin in patients with metabolic syndrome</article-title>
          <source>Cytokine</source>
          <year>2011</year>
          <volume>54</volume>
          <issue>2</issue>
          <fpage>185</fpage>
          <lpage>190</lpage>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4 Tok D, Kadife I, Turak O, Ozcan F, Basar N, Cagli K, et al. Increased epicardial fat thickness is associated with low grade systemic inflammation in metabolic syndrome. Turk Kardiyol Dern Ars. 2012;40(8):690-5.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tok</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Kadife</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Turak</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Ozcan</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Basar</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Cagli</surname>
              <given-names>K</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Increased epicardial fat thickness is associated with low grade systemic inflammation in metabolic syndrome</article-title>
          <source>Turk Kardiyol Dern Ars</source>
          <year>2012</year>
          <volume>40</volume>
          <issue>8</issue>
          <fpage>690</fpage>
          <lpage>695</lpage>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5 Eroglu S, Sade LE, Yildirir A, Demir &#214;, M&#252;derrisoglu H. Association of epicardial adipose tissue thickness by echocardiography and hypertension. Turk Kardiyol Dern Ars. 2013;41(2):115-22.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Eroglu</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Sade</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Yildirir</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Demir</surname>
              <given-names>&#214;</given-names>
            </name>
            <name>
              <surname>M&#252;derrisoglu</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
          <article-title>Association of epicardial adipose tissue thickness by echocardiography and hypertension</article-title>
          <source>Turk Kardiyol Dern Ars</source>
          <year>2013</year>
          <volume>41</volume>
          <issue>2</issue>
          <fpage>115</fpage>
          <lpage>122</lpage>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6 Sacks HS, Fain JN. Human epicardial fat: what is new and what is missing? Clin Exp Pharmacol Physiol. 2011;38(12):879-87.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sacks</surname>
              <given-names>HS</given-names>
            </name>
            <name>
              <surname>Fain</surname>
              <given-names>JN</given-names>
            </name>
          </person-group>
          <article-title>Human epicardial fat: what is new and what is missing?</article-title>
          <source>Clin Exp Pharmacol Physiol</source>
          <year>2011</year>
          <volume>38</volume>
          <issue>12</issue>
          <fpage>879</fpage>
          <lpage>887</lpage>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7 Shemirani H, Khoshavi M. Correlation of echocardiographic epicardial fat thickness with severity of coronary artery disease-an observational study. Anadolu Kardiyol Derg. 2012;12(3):200-5</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Shemirani</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Khoshavi</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Correlation of echocardiographic epicardial fat thickness with severity of coronary artery disease-an observational study</article-title>
          <source>Anadolu Kardiyol Derg</source>
          <year>2012</year>
          <volume>12</volume>
          <issue>3</issue>
          <fpage>200</fpage>
          <lpage>205</lpage>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8 Ahn SG, Lim HS, Joe DY, Kang SJ, Choi BJ, Choi SY, et al. Relationship of epicardial adipose tissue by echocardiography to coronary artery disease. Heart. 2008;94(3):e7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ahn</surname>
              <given-names>SG</given-names>
            </name>
            <name>
              <surname>Lim</surname>
              <given-names>HS</given-names>
            </name>
            <name>
              <surname>Joe</surname>
              <given-names>DY</given-names>
            </name>
            <name>
              <surname>Kang</surname>
              <given-names>SJ</given-names>
            </name>
            <name>
              <surname>Choi</surname>
              <given-names>BJ</given-names>
            </name>
            <name>
              <surname>Choi</surname>
              <given-names>SY</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Relationship of epicardial adipose tissue by echocardiography to coronary artery disease</article-title>
          <source>Heart</source>
          <year>2008</year>
          <volume>94</volume>
          <issue>3</issue>
          <elocation-id>e7</elocation-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9 Aykan A&#199;, G&#252;l I, G&#246;kdeniz T, Hatem E, Arslan AO, Kalaycioglu E, et al. Ankle brachial index intensifies the diagnostic accuracy of epicardial fat thickness for the prediction of coronary artery disease complexity. Heart Lung Circ. 2014;23(8):764-71.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Aykan</surname>
              <given-names>A&#199;</given-names>
            </name>
            <name>
              <surname>G&#252;l</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>G&#246;kdeniz</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Hatem</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Arslan</surname>
              <given-names>AO</given-names>
            </name>
            <name>
              <surname>Kalaycioglu</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Ankle brachial index intensifies the diagnostic accuracy of epicardial fat thickness for the prediction of coronary artery disease complexity</article-title>
          <source>Heart Lung Circ</source>
          <year>2014</year>
          <volume>23</volume>
          <issue>8</issue>
          <fpage>764</fpage>
          <lpage>771</lpage>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10 Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al; SYNTAX Investigators. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961-72. Erratum in: N Engl J Med. 2013;368(6):584.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Serruys</surname>
              <given-names>PW</given-names>
            </name>
            <name>
              <surname>Morice</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Kappetein</surname>
              <given-names>AP</given-names>
            </name>
            <name>
              <surname>Colombo</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Holmes</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Mack</surname>
              <given-names>MJ</given-names>
            </name>
            <collab>SYNTAX Investigators</collab>
            <etal/>
          </person-group>
          <article-title>Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease</article-title>
          <source>N Engl J Med</source>
          <year>2009</year>
          <volume>360</volume>
          <issue>10</issue>
          <fpage>961</fpage>
          <lpage>972</lpage>
          <comment>Erratum in N Engl J Med. 2013;368(6):584</comment>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11 G&#246;kdeniz T, Turan T, Aykan A&#199;, G&#252;l I, Boyaci F, Hatem E, et al. Relation of epicardial fat thickness and cardio-ankle vascular index to complexity of coronary artery disease in nondiabetic patients.Cardiology. 2013;124(1):41-8.</mixed-citation>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>G&#246;kdeniz</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Turan</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Aykan</surname>
              <given-names>A&#199;</given-names>
            </name>
            <name>
              <surname>G&#252;l</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Boyaci</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Hatem</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <chapter-title>Relation of epicardial fat thickness and cardio-ankle vascular index to complexity of coronary artery disease in nondiabetic patients</chapter-title>
          <source>Cardiology</source>
          <year>2013</year>
          <volume>124</volume>
          <issue>1</issue>
          <fpage>41</fpage>
          <lpage>48</lpage>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12 Iacobellis G, Assael F, Ribaudo MC, Zappaterreno A, Alessi G, Di Mario U, et al. Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction. Obes Res. 2003;11(2):304-10.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Iacobellis</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Assael</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Ribaudo</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Zappaterreno</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Alessi</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Di Mario</surname>
              <given-names>U</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction</article-title>
          <source>Obes Res</source>
          <year>2003</year>
          <volume>11</volume>
          <issue>2</issue>
          <fpage>304</fpage>
          <lpage>310</lpage>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13 Miller D, Farah MG, Liner A, Fox K, Schluchter M, Hoit BD. The relation between quantitative right ventricular ejection fraction and indices of tricuspid annular motion and myocardial performance. J Am Soc Echocardiogr. 2004;17(5):443-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Miller</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Farah</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Liner</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Fox</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Schluchter</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Hoit</surname>
              <given-names>BD</given-names>
            </name>
          </person-group>
          <article-title>The relation between quantitative right ventricular ejection fraction and indices of tricuspid annular motion and myocardial performance</article-title>
          <source>J Am Soc Echocardiogr</source>
          <year>2004</year>
          <volume>17</volume>
          <issue>5</issue>
          <fpage>443</fpage>
          <lpage>447</lpage>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14 Tei C, Dujardin KS, Hodge DO, Bailey KR, McGoon MD, Tajik AJ, et al. Doppler echocardiographic index for assessment of global right ventricular function. J Am Soc Echocardiogr .1996;9(6):838-47.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tei</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Dujardin</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Hodge</surname>
              <given-names>DO</given-names>
            </name>
            <name>
              <surname>Bailey</surname>
              <given-names>KR</given-names>
            </name>
            <name>
              <surname>McGoon</surname>
              <given-names>MD</given-names>
            </name>
            <name>
              <surname>Tajik</surname>
              <given-names>AJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Doppler echocardiographic index for assessment of global right ventricular function</article-title>
          <source>J Am Soc Echocardiogr</source>
          <year>1996</year>
          <volume>9</volume>
          <issue>6</issue>
          <fpage>838</fpage>
          <lpage>847</lpage>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15 Granger CB, Goldberg RJ, Dabbous OH, Pieper KS, Eagle KA, Cannon CP, et al; Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163(19):2345-53.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Granger</surname>
              <given-names>CB</given-names>
            </name>
            <name>
              <surname>Goldberg</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Dabbous</surname>
              <given-names>OH</given-names>
            </name>
            <name>
              <surname>Pieper</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Eagle</surname>
              <given-names>KA</given-names>
            </name>
            <name>
              <surname>Cannon</surname>
              <given-names>CP</given-names>
            </name>
            <etal/>
            <collab>Global Registry of Acute Coronary Events Investigators</collab>
          </person-group>
          <article-title>Predictors of hospital mortality in the global registry of acute coronary events</article-title>
          <source>Arch Intern Med</source>
          <year>2003</year>
          <volume>163</volume>
          <issue>19</issue>
          <fpage>2345</fpage>
          <lpage>2353</lpage>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16 Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ. 2006;333(7578):1091.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fox</surname>
              <given-names>KA</given-names>
            </name>
            <name>
              <surname>Dabbous</surname>
              <given-names>OH</given-names>
            </name>
            <name>
              <surname>Goldberg</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Pieper</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Eagle</surname>
              <given-names>KA</given-names>
            </name>
            <name>
              <surname>Van de Werf</surname>
              <given-names>F</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE)</article-title>
          <source>BMJ</source>
          <year>2006</year>
          <volume>333</volume>
          <issue>7578</issue>
          <fpage>1091</fpage>
          <lpage>1091</lpage>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17 Iacobellis G, Willens HJ. Echocardiographic epicardial fat: a review of research and clinical applications. J Am Soc Echocardiogr. 2009;22(12):1311-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Iacobellis</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Willens</surname>
              <given-names>HJ</given-names>
            </name>
          </person-group>
          <article-title>Echocardiographic epicardial fat: a review of research and clinical applications</article-title>
          <source>J Am Soc Echocardiogr</source>
          <year>2009</year>
          <volume>22</volume>
          <issue>12</issue>
          <fpage>1311</fpage>
          <lpage>1319</lpage>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18 Sacks HS, Fain JN, Cheema P, Bahouth SW, Garrett E, Wolf RY, et al. Depot-specific overexpression of proinflammatory, redox, endothelial cell and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis. Metab Syndr Relat Disord. 2011;9(6):433-9</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sacks</surname>
              <given-names>HS</given-names>
            </name>
            <name>
              <surname>Fain</surname>
              <given-names>JN</given-names>
            </name>
            <name>
              <surname>Cheema</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Bahouth</surname>
              <given-names>SW</given-names>
            </name>
            <name>
              <surname>Garrett</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Wolf</surname>
              <given-names>RY</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Depot-specific overexpression of proinflammatory, redox, endothelial cell and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis</article-title>
          <source>Metab Syndr Relat Disord</source>
          <year>2011</year>
          <volume>9</volume>
          <issue>6</issue>
          <fpage>433</fpage>
          <lpage>439</lpage>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19 Spiroglou SG, Kostopoulos CG, Varakis JN, Papadaki HH, et al. Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J Atheroscler Thromb. 2010;17(2):115-30.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Spiroglou</surname>
              <given-names>SG</given-names>
            </name>
            <name>
              <surname>Kostopoulos</surname>
              <given-names>CG</given-names>
            </name>
            <name>
              <surname>Varakis</surname>
              <given-names>JN</given-names>
            </name>
            <name>
              <surname>Papadaki</surname>
              <given-names>HH</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis</article-title>
          <source>J Atheroscler Thromb</source>
          <year>2010</year>
          <volume>17</volume>
          <issue>2</issue>
          <fpage>115</fpage>
          <lpage>130</lpage>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20 Nabati M, Saffar N, Yazdani J, Parsaee MS. Relationship between epicardial fat measured by echocardiography and coronary atherosclerosis: a single-blind historical cohort study. Echocardiography. 2013;30(5):505-11.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nabati</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Saffar</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Yazdani</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Parsaee</surname>
              <given-names>MS</given-names>
            </name>
          </person-group>
          <article-title>Relationship between epicardial fat measured by echocardiography and coronary atherosclerosis: a single-blind historical cohort study</article-title>
          <source>Echocardiography</source>
          <year>2013</year>
          <volume>30</volume>
          <issue>5</issue>
          <fpage>505</fpage>
          <lpage>511</lpage>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>21 Tanindi A, Kocaman SA, Erkan AF, Ugurlu M, Alhan A, T&#246;re HF. Epicardial adipose tissue thickness is associated with myocardial infarction and impaired coronary perfusion. Anatol J Cardiol. 2015;15(3):224-31.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tanindi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kocaman</surname>
              <given-names>SA</given-names>
            </name>
            <name>
              <surname>Erkan</surname>
              <given-names>AF</given-names>
            </name>
            <name>
              <surname>Ugurlu</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Alhan</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>T&#246;re</surname>
              <given-names>HF</given-names>
            </name>
          </person-group>
          <article-title>Epicardial adipose tissue thickness is associated with myocardial infarction and impaired coronary perfusion</article-title>
          <source>Anatol J Cardiol</source>
          <year>2015</year>
          <volume>15</volume>
          <issue>3</issue>
          <fpage>224</fpage>
          <lpage>231</lpage>
        </element-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <mixed-citation>22 Pracon R, Kruk M, Kepka C, Pregowski J, Opolski MP, Dzielinska Z, et al. Epicardial adipose tissue radiodensity is independently related to coronary atherosclerosis. A multidetector computed tomography study. Circ J. 2011;75(2):391-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pracon</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Kruk</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Kepka</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Pregowski</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Opolski</surname>
              <given-names>MP</given-names>
            </name>
            <name>
              <surname>Dzielinska</surname>
              <given-names>Z</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Epicardial adipose tissue radiodensity is independently related to coronary atherosclerosis. A multidetector computed tomography study</article-title>
          <source>Circ J</source>
          <year>2011</year>
          <volume>75</volume>
          <issue>2</issue>
          <fpage>391</fpage>
          <lpage>397</lpage>
        </element-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <mixed-citation>23 Karadag B, Ozulu B, Ozturk FY, Oztekin E, Sener N, Altuntas Y, et al. Comparison of epicardial adipose tissue (EAT) thickness and anthropometric measurements in metabolic syndrome (MS) cases above and under the age of 65. Arch Gerontol Geriatr 2011;52(2):e79-84.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Karadag</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Ozulu</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Ozturk</surname>
              <given-names>FY</given-names>
            </name>
            <name>
              <surname>Oztekin</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Sener</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Altuntas</surname>
              <given-names>Y</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Comparison of epicardial adipose tissue (EAT) thickness and anthropometric measurements in metabolic syndrome (MS) cases above and under the age of 65</article-title>
          <source>Arch Gerontol Geriatr</source>
          <year>2011</year>
          <volume>52</volume>
          <issue>2</issue>
          <fpage>e79</fpage>
          <lpage>e84</lpage>
        </element-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <mixed-citation>24 de Vos AM, Prokop M, Roos CJ, Meijs MF, van der Schouw YT, Rutten A, et al. Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women. Eur Heart J. 2008;29(6):777-83.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>de Vos</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Prokop</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Roos</surname>
              <given-names>CJ</given-names>
            </name>
            <name>
              <surname>Meijs</surname>
              <given-names>MF</given-names>
            </name>
            <name>
              <surname>van der Schouw</surname>
              <given-names>YT</given-names>
            </name>
            <name>
              <surname>Rutten</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women</article-title>
          <source>Eur Heart J</source>
          <year>2008</year>
          <volume>29</volume>
          <issue>6</issue>
          <fpage>777</fpage>
          <lpage>783</lpage>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>25 Erdogan T, &#199;etin M, Kocaman SA, Durakoglugil ME, Erg&#252;l E, Ugurlu Y, et al. Epicardial adipose tissue is independently associated with increased left ventricular mass in untreated hypertensive patients: an observational study. Anadolu Kardiyol Derg. 2013;13(4):320-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Erdogan</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>&#199;etin</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Kocaman</surname>
              <given-names>SA</given-names>
            </name>
            <name>
              <surname>Durakoglugil</surname>
              <given-names>ME</given-names>
            </name>
            <name>
              <surname>Erg&#252;l</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Ugurlu</surname>
              <given-names>Y</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Epicardial adipose tissue is independently associated with increased left ventricular mass in untreated hypertensive patients: an observational study</article-title>
          <source>Anadolu Kardiyol Derg</source>
          <year>2013</year>
          <volume>13</volume>
          <issue>4</issue>
          <fpage>320</fpage>
          <lpage>327</lpage>
        </element-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <mixed-citation>26 Lin YK, Chen YJ, Chen SA. Potential atrial arrhythmogenicity of adipocytes: implications for the genesis of atrial fibrillation. Med Hypotheses. 2010;74(6):1026-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lin</surname>
              <given-names>YK</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>YJ</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>SA</given-names>
            </name>
          </person-group>
          <article-title>Potential atrial arrhythmogenicity of adipocytes: implications for the genesis of atrial fibrillation</article-title>
          <source>Med Hypotheses</source>
          <year>2010</year>
          <volume>74</volume>
          <issue>6</issue>
          <fpage>1026</fpage>
          <lpage>1029</lpage>
        </element-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <mixed-citation>27 Tok D, &#214;zcan F, Kadife I, Turak O, &#199;agli K, Basar N, et al. Impaired coronary flow reserve evaluated by echocardiography is associated with increased aortic stiffness in patients with metabolic syndrome: an observational study. Anadolu Kardiyol Derg. 2013;13(3):227-34.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tok</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>&#214;zcan</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Kadife</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Turak</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>&#199;agli</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Basar</surname>
              <given-names>N</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Impaired coronary flow reserve evaluated by echocardiography is associated with increased aortic stiffness in patients with metabolic syndrome: an observational study</article-title>
          <source>Anadolu Kardiyol Derg</source>
          <year>2013</year>
          <volume>13</volume>
          <issue>3</issue>
          <fpage>227</fpage>
          <lpage>234</lpage>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Rela&#231;&#227;o entre Escore GRACE e Espessura da Gordura Epic&#225;rdica em Pacientes com IMSSST</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gul</surname>
            <given-names>Ilker</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Zungur</surname>
            <given-names>Mustafa</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Aykan</surname>
            <given-names>Ahmet Cagri</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gokdeniz</surname>
            <given-names>Teyyar</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kalaycio&#287;lu</surname>
            <given-names>Ezgi</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Turan</surname>
            <given-names>Turhan</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hatem</surname>
            <given-names>Engin</given-names>
          </name>
          <xref ref-type="aff" rid="aff9">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Boyaci</surname>
            <given-names>Faruk</given-names>
          </name>
          <xref ref-type="aff" rid="aff10">5</xref>
        </contrib>
      </contrib-group>
      <aff id="aff6">
        <label>1</label>
        <institution content-type="original">&#350;ifa University Faculty of Medicine - Department of Cardiology, Izmir - Turquia</institution>
      </aff>
      <aff id="aff7">
        <label>2</label>
        <institution content-type="original">Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital - Department of Cardiology, Trabzon - Turquia</institution>
      </aff>
      <aff id="aff8">
        <label>3</label>
        <institution content-type="original">Kafkas University Faculty of Medicine - Department of Cardiology, Kars - Turquia</institution>
      </aff>
      <aff id="aff9">
        <label>4</label>
        <institution content-type="original">Erzurum Region Education and Research Hospital, Erzurum - Turquia</institution>
      </aff>
      <aff id="aff10">
        <label>5</label>
        <institution content-type="original">Samsun Education and Research Hospital, Samsun - Turquia</institution>
      </aff>
      <author-notes>
        <corresp id="c2">Correspond&#234;ncia para: Ilker Gul, Sifa University Faculty of Medicine Bornova Hospital, Postal Code 35040, &#304;zmir - Turquia. E-mail: <email>drilkergul46@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Zungur M, Gul I, Zungur M, Aykan AC, Gokdeniz T, Kalaycio&#287;lu E, Turan T, Boyaci F; Obten&#231;&#227;o de dados: Gul I, Zungur M, Aykan AC, Turan T, Hatem E; An&#225;lise e interpreta&#231;&#227;o dos dados: Gul I, Zungur M, Aykan AC, Kalaycio&#287;lu E, Hatem E, Boyaci F; An&#225;lise estat&#237;stica: Gul I, Zungur M, Aykan AC, Gokdeniz T, Kalaycio&#287;lu E, Turan T, Hatem E; Reda&#231;&#227;o do manuscrito: Gul I; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Gul I, Zungur M, Aykan AC, Gokdeniz T.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>O escore de risco GRACE (SG) &#233; um sistema com significado progn&#243;stico para pacientes com infarto do mioc&#225;rdio sem supradesnivelamento do segmento ST (IMSSST).</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Determinar se a espessura da gordura epic&#225;rdica (EGE) ao final da s&#237;stole ou da di&#225;stole &#233; mais associada com pacientes de IMSSST de alto risco de acordo com o SG.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Este estudo avaliou 207 pacientes com IMSSST desde outubro de 2012 a fevereiro de 2013, sendo 162 deles inclu&#237;dos no estudo (115 homens, idade m&#233;dia: 66,6 &#177; 12,8 anos). Mediu-se a EGE ao final da s&#237;stole e da di&#225;stole com m&#233;todos ecocardiogr&#225;ficos. Pacientes com alto SG intra-hospitalar (SG &gt; 140) foram classificados como grupo SG-A, enquanto os outros foram classificados como grupo de risco baixo-a-moderado (grupo SG-BM).</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>As press&#245;es arteriais sist&#243;lica e diast&#243;lica dos pacientes SG-A foram mais baixas do que as dos pacientes SG-BM, sendo a frequ&#234;ncia card&#237;aca m&#233;dia mais alta nesse grupo. A EGE ao final da s&#237;stole e a EGE ao final da di&#225;stole foram significativamente mais altas no grupo SG-A. A avalia&#231;&#227;o ecocardiogr&#225;fica dos ventr&#237;culos direito e esquerdo mostrou fra&#231;&#227;o de eje&#231;&#227;o significativamente reduzida em ambos os ventr&#237;culos no grupo SG-A. Observou-se maior correla&#231;&#227;o entre SG e EGE ao final da di&#225;stole (r = 0,438).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>A EGE ao final da s&#237;stole e a EGE ao final da di&#225;stole mostraram-se aumentadas no grupo SG-A. Entretanto, a EGE ao final da di&#225;stole apresentou melhor correla&#231;&#227;o com o SG do que a EGE ao final da s&#237;stole.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>S&#237;ndrome Coronariana Aguda</kwd>
        <kwd>Tecido Adiposo</kwd>
        <kwd>Infarto do Mioc&#225;rdio</kwd>
        <kwd>Ecocardiografia</kwd>
        <kwd>Peric&#225;rdio</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>V&#225;rios sistemas de escore foram desenvolvidos para avalia&#231;&#227;o progn&#243;stica de pacientes hospitalizados com s&#237;ndrome coronariana aguda (SCA). As diretrizes da <italic>American Heart Association</italic> (AHA) e da Sociedade Europeia de Cardiologia (ESC) enfatizam a import&#226;ncia progn&#243;stica do escore de risco GRACE (SG), e recomendam seu uso rotineiro. O SG pode ser calculado para o per&#237;odo intra-hospitalar e para os seis meses que se seguem &#224; alta. Um SG intra-hospitalar &gt; 140 &#233; considerado um risco aumentado em termos de mortalidade. Interven&#231;&#227;o precoce e terapia de revasculariza&#231;&#227;o s&#227;o recomendadas para esses pacientes.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref>
				</p>
        <p>Sabe-se que o tecido adiposo visceral tem fun&#231;&#227;o end&#243;crina e atividade metab&#243;lica. O tecido adiposo epic&#225;rdico &#233; um tipo de tecido adiposo visceral que se estende ao longo das art&#233;rias coron&#225;rias. Recentemente, uma crescente quantidade de dados tem demonstrado a import&#226;ncia da espessura da gordura epic&#225;rdica (EGE). Seu aumento acha-se associado com hipertens&#227;o, resist&#234;ncia insul&#237;nica e processos inflamat&#243;rios, como diabetes mellitus e s&#237;ndrome metab&#243;lica.<xref ref-type="bibr" rid="B3">3</xref><sup>-</sup><xref ref-type="bibr" rid="B5">5</xref> Como resultado dos estudos investigando a rela&#231;&#227;o entre EGE e doen&#231;a arterial coronariana (DAC), a EGE associou-se com gravidade e carga da DAC.<xref ref-type="bibr" rid="B6">6</xref><sup>-</sup><xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <p>A EGE pode ser medida por resson&#226;ncia nuclear magn&#233;tica (RNM) e tomografia computadorizada com multidetectores (TC). Entretanto, esses exames s&#227;o onerosos e n&#227;o se prestam para uso rotineiro. A ecocardiografia tem pre&#231;o reduzido e boa disponibilidade, sendo de f&#225;cil execu&#231;&#227;o quando comparada &#224; RNM e &#224; TC. Por essas raz&#245;es, a maioria dos estudos pr&#233;vios calculou a EGE usando m&#233;todos ecocardiogr&#225;ficos. N&#227;o h&#225; consenso quanto &#224; fase do ciclo card&#237;aco em que se deve medir a EGE. Embora alguns estudos sugiram que tais medidas devam ser tomadas no final da s&#237;stole,<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> um maior n&#250;mero recomenda que sejam realizadas ao final da di&#225;stole.<xref ref-type="bibr" rid="B5">5</xref><sup>-</sup><xref ref-type="bibr" rid="B8">8</xref>
				</p>
        <p>O presente estudo visou a determinar se a EGE ao final da s&#237;stole ou da di&#225;stole acha-se mais intimamente associada com pacientes com infarto do mioc&#225;rdio sem supradesnivelamento do segmento ST (IMSSST) de alto risco segundo o SG.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Este estudo observacional prospectivo foi realizado entre outubro de 2012 e fevereiro de 2013. Os pacientes apresentando IMSSST pela primeira vez foram inclu&#237;dos. Foram exclu&#237;dos aqueles com doen&#231;a pulmonar cr&#244;nica, doen&#231;a hep&#225;tica cr&#244;nica, doen&#231;a inflamat&#243;ria reum&#225;tica, doen&#231;a muscular, insufici&#234;ncia card&#237;aca, insufici&#234;ncia renal cr&#244;nica (creatinina &gt; 2,5 mg/dL), miocardite e cardiomiopatia.</p>
        <p>Diagnosticou-se IMSSST na presen&#231;a de um padr&#227;o de angina acelerada ou prolongada ou recorrente tanto de repouso quanto durante os m&#237;nimos esfor&#231;os nas &#250;ltimas 48-72 horas, com n&#237;veis de troponina ou creatino quinase-MB (CK-MB) acima dos limites superiores da normalidade. Os par&#226;metros bioqu&#237;micos foram avaliados em amostras de sangue coletadas durante a hospitaliza&#231;&#227;o. Os n&#237;veis m&#225;ximos de cTnI e CK-MB foram identificados durante o seguimento das enzimas card&#237;acas.</p>
        <p>Usou-se um programa de computador (<ext-link ext-link-type="uri" xlink:href="http://www.outcomes-umassmed.org/grace/acs_risco">www.outcomes-umassmed.org/grace/acs_risco</ext-link>) para calcular o SG. Idade, press&#227;o arterial sist&#243;lica, n&#237;vel s&#233;rico de creatinina e classifica&#231;&#227;o de Killip foram determinados para o SG. Os seguintes dados foram utilizados no programa de computador: parada card&#237;aca na admiss&#227;o, altera&#231;&#245;es do segmento ST, m&#233;todo de revasculariza&#231;&#227;o e informa&#231;&#227;o sobre eleva&#231;&#227;o das enzimas card&#237;acas. Ap&#243;s o c&#225;lculo dos valores do SG, os pacientes foram divididos em grupos conforme a recomenda&#231;&#227;o das diretrizes da AHA e da ESC sobre IMSSST.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref>
				</p>
        <p>Os pacientes com SG intra-hospitalar de baixo a moderado (&lt; 140) foram classificados como o grupo SG-BM (n = 70), e aqueles com SG intra-hospitalar alto (&gt; 140), como grupo SG-A (n = 92).</p>
        <sec>
          <title>Ecocardiografia</title>
          <p>As caracter&#237;sticas basais cl&#237;nicas (frequ&#234;ncia card&#237;aca, press&#227;o arterial, eletrocardiografia, par&#226;metros bioqu&#237;micos laboratoriais, angiografia), ecocardiogr&#225;ficas e demogr&#225;ficas (idade, sexo, altura, peso) dos pacientes foram registradas. A vari&#225;vel preditora foi o SG, e a vari&#225;vel desfecho prim&#225;rio foi a EGE.</p>
          <p>Realizou-se an&#225;lise ecocardiogr&#225;fica na posi&#231;&#227;o de dec&#250;bito lateral esquerdo conforme a recomenda&#231;&#227;o das diretrizes da Sociedade Americana de Ecocardiografia, nas primeiras 24 horas de terapia intensiva, usando o sistema de ultrassom cardiovascular Vivid S5 (General Electric Vingmed Ultrasound, Horten, Noruega). A gordura epic&#225;rdica foi definida como um espa&#231;o "sem eco" entre a parede externa do mioc&#225;rdio e a camada visceral do peric&#225;rdio. O maior di&#226;metro da gordura epic&#225;rdica localizada na parede livre do ventr&#237;culo direito (VD) foi determinado. A EGE foi medida no corte longitudinal parasternal no final da s&#237;stole e no final da di&#225;stole em tr&#234;s ciclos card&#237;acos. A m&#233;dia dos tr&#234;s ciclos card&#237;acos foi usada para a an&#225;lise estat&#237;stica.</p>
          <p>A fra&#231;&#227;o de eje&#231;&#227;o (FE) ventricular esquerda foi determinada usando-se o m&#233;todo de Simpson modificado. Para uma melhor avalia&#231;&#227;o das fun&#231;&#245;es do VD, calculou-se a excurs&#227;o sist&#243;lica do plano anular tric&#250;spide (TAPSE) a partir do anel lateral tric&#250;spide.<xref ref-type="bibr" rid="B13">13</xref> A FEVD foi calculada com ecocardiografia 3D, usando-se o m&#233;todo de soma&#231;&#227;o de discos. O &#237;ndice de desempenho mioc&#225;rdico, conhecido como &#237;ndice Tei, &#233; uma estimativa global das duas fun&#231;&#245;es do VD. O &#237;ndice Tei &#233; um &#237;ndice de intervalo de tempo derivado do Doppler, que combina o desempenho card&#237;aco sist&#243;lico e diast&#243;lico. O &#237;ndice Tei &#233; facilmente derivado usando-se ecocardiografia Doppler convencional pulsada, como previamente descrito por Tei et al.<xref ref-type="bibr" rid="B14">14</xref>
					</p>
          <p>O presente estudo foi planejado e conduzido de acordo com a Declara&#231;&#227;o de Helsinque, tendo seu protocolo sido aprovado pelo Comit&#234; de &#201;tica.</p>
        </sec>
        <sec>
          <title>An&#225;lise de variabilidade</title>
          <p>As variabilidades intra- e inter-observador foram verificadas para os dados ecocardiogr&#225;ficos obtidos para um subgrupo de 40 indiv&#237;duos. Um dia depois, o primeiro operador repetiu a an&#225;lise para avaliar a variabilidade intra-observador. Para avaliar a variabilidade inter-observador, um segundo operador cego para as medidas anteriores verificou cada par&#226;metro dois dias mais tarde. A an&#225;lise de concord&#226;ncia para variabilidade intra- e inter-observador das medidas de EGE revelou um alto n&#237;vel de concord&#226;ncia com diferen&#231;a m&#233;dia de 0,26 (limite de concord&#226;ncia 95%: -0,5 a 0,93) e coeficiente de correla&#231;&#227;o intraclasse de 0,918 (IC 95%: 0,830-0,960).</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Os dados categ&#243;ricos s&#227;o apresentados como frequ&#234;ncias (porcentagens) e as vari&#225;veis cont&#237;nuas, como m&#233;dia &#177; DP. O teste de Kolmogorov-Smirnov foi usado para avaliar se os dados tinham uma distribui&#231;&#227;o normal. Como a distribui&#231;&#227;o foi normal, usou-se o teste <italic>t</italic> para amostras independentes para a an&#225;lise estat&#237;stica. Realizou-se o teste do qui-quadrado para as vari&#225;veis categ&#243;ricas. Coeficientes de correla&#231;&#227;o intraclasse e an&#225;lise de Bland-Altman foram usados para as medidas ecocardiogr&#225;ficas para avaliar a reprodutibilidade intra- e inter-observador, respectivamente. O teste de Pearson foi usado para analizar a correla&#231;&#227;o entre SG e EGE. Construiu-se curva <italic>receiver operating characteristic</italic> (ROC) para determinar se a EGE podia predizer os grupos de alto risco com base no SG. Um p bicaudal &lt; 0,05 foi considerado estatisticamente significativo.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Dados demogr&#225;ficos e caracter&#237;sticas basais</title>
          <p>Este estudo avaliou 207 pacientes admitidos com IMSSST, sendo 45 exclu&#237;dos devido &#224;s seguintes condi&#231;&#245;es: doen&#231;a pulmonar cr&#244;nica, 22 pacientes; doen&#231;a hep&#225;tica cr&#244;nica, 2; insufici&#234;ncia card&#237;aca pr&#233;via, 10; insufici&#234;ncia renal cr&#244;nica, 8; miocardite, 2; e cardiomiopatia, 1. No total, 162 pacientes foram inclu&#237;dos no estudo (115 homens; idade m&#233;dia, 63,9&#177;12,8 anos). Com base no SG intra-hospitalar, 70 pacientes foram classificados como do grupo SG-BM, e 92, como do grupo SG-A. A idade m&#233;dia foi maior no grupo SG-A (73,7 &#177; 10,5 vs. 57,2 &#177; 9,1 anos; p &lt; 0,001). A press&#227;o arterial sist&#243;lica m&#233;dia (147,3 &#177; 27,7 vs. 130,3 &#177; 31,1 mmHg; p &lt; 0,001) e a press&#227;o arterial diast&#243;lica m&#233;dia (85,5 &#177; 16,1 vs. 78,1 &#177; 19,5 mmHg; p = 0,010) foram mais altas no grupo SG-BM. N&#227;o houve diferen&#231;a entre os grupos quanto ao &#237;ndice de massa corporal, tabagismo e n&#250;mero de pacientes com hipertens&#227;o e diabetes mellitus. Taxa de mortalidade [3 (4,3%) vs. 13 (14,1%); p = 0,037], perman&#234;ncia na unidade de terapia intensiva [3,3 &#177; 1,2 dias vs. 4,3 &#177; 2,9 dias; p = 0,019] e perman&#234;ncia total hospitalar [5,6 &#177; 2,5 dias vs. 6,9 &#177; 3,8 dias; p = 0,020] foram significativamente mais altas no grupo SG-A do que no grupo SG-BM (<xref ref-type="table" rid="t4">Tabela 1</xref>).</p>
          <table-wrap id="t4">
            <label>Tabela 1</label>
            <caption>
              <title>Caracter&#237;sticas gerais dos pacientes com infarto mioc&#225;rdico sem supradesnivelamento do segmento ST de acordo com o escore GRACE intra-hospitalar</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th>
									</th>
                  <th align="center">
                    <bold>Grupo de risco baixo-a-moderado (n = 70)</bold>
                  </th>
                  <th align="center">
                    <bold>Grupo de risco alto (n = 92)</bold>
                  </th>
                  <th align="center">
                    <bold>Valor de p</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Idade, anos</td>
                  <td align="center">57,2 &#177; 9,1</td>
                  <td align="center">73,7 &#177; 10,5</td>
                  <td align="center">p &lt; 0,001</td>
                </tr>
                <tr>
                  <td>Sexo, masculino/feminino</td>
                  <td align="center">56/14</td>
                  <td align="center">59/33</td>
                  <td align="center">p = 0,027</td>
                </tr>
                <tr>
                  <td>Press&#227;o arterial sist&#243;lica, mmHg</td>
                  <td align="center">147,3 &#177; 27,7</td>
                  <td align="center">130,3 &#177; 31,1</td>
                  <td align="center">p &lt; 0,001</td>
                </tr>
                <tr>
                  <td>Press&#227;o arterial diast&#243;lica, mmHg</td>
                  <td align="center">85,5 &#177; 16,1</td>
                  <td align="center">78,1 &#177; 19,5</td>
                  <td align="center">p = 0,010</td>
                </tr>
                <tr>
                  <td>&#205;ndice de massa corporal, kg/m<sup>2</sup></td>
                  <td align="center">28,5 &#177; 4,4</td>
                  <td align="center">26,7 &#177; 3,7</td>
                  <td align="center">p = 0,060</td>
                </tr>
                <tr>
                  <td>Tabagismo, n (%)</td>
                  <td align="center">35 (50%)</td>
                  <td align="center">50 (54,1%)</td>
                  <td align="center">p = 0,583</td>
                </tr>
                <tr>
                  <td>Hipertens&#227;o, n (%)</td>
                  <td align="center">40 (57,1%)</td>
                  <td align="center">44 (47,8%)</td>
                  <td align="center">p = 0,299</td>
                </tr>
                <tr>
                  <td>Diabetes mellitus, n (%)</td>
                  <td align="center">21 (30,0%)</td>
                  <td align="center">33 (35,9%)</td>
                  <td align="center">p = 0,376</td>
                </tr>
                <tr>
                  <td>Glicemia na admiss&#227;o, mg/dL</td>
                  <td align="center">139,6 &#177; 60,3</td>
                  <td align="center">146,5 &#177; 70,3</td>
                  <td align="center">p = 0,515</td>
                </tr>
                <tr>
                  <td>Colesterol total, mg/dL</td>
                  <td align="center">185,7 &#177; 44,9</td>
                  <td align="center">204,2 &#177; 55,9</td>
                  <td align="center">p = 0,022</td>
                </tr>
                <tr>
                  <td>LDL colesterol, mg/dL</td>
                  <td align="center">133,1 &#177; 37,9</td>
                  <td align="center">148,5 &#177; 43,9</td>
                  <td align="center">p = 0,019</td>
                </tr>
                <tr>
                  <td>HDL colesterol, mg/dL</td>
                  <td align="center">40,9 &#177; 15,9</td>
                  <td align="center">39,9 &#177; 9,8</td>
                  <td align="center">p = 0,627</td>
                </tr>
                <tr>
                  <td>Triglicer&#237;deos, mg/dL</td>
                  <td align="center">124,8 &#177; 71,4</td>
                  <td align="center">131,3 &#177; 96,8</td>
                  <td align="center">p = 0,641</td>
                </tr>
                <tr>
                  <td>Prote&#237;na C Reativa, mg/dL</td>
                  <td align="center">1,63 &#177; 3,4</td>
                  <td align="center">2,68 &#177; 4,38</td>
                  <td align="center">p = 0,013</td>
                </tr>
                <tr>
                  <td>Creatinina, mg/dL</td>
                  <td align="center">0,84 &#177; 0,2</td>
                  <td align="center">1,18 &#177; 0,57</td>
                  <td align="center">p &lt; 0,001</td>
                </tr>
                <tr>
                  <td>Troponina I, ng/mL</td>
                  <td align="center">31,6 &#177; 30,0</td>
                  <td align="center">31,1 &#177; 28,1</td>
                  <td align="center">p = 0,951</td>
                </tr>
                <tr>
                  <td>Fra&#231;&#227;o de eje&#231;&#227;o VE, %</td>
                  <td align="center">47,8 &#177; 10,2</td>
                  <td align="center">43,3 &#177; 10,5</td>
                  <td align="center">p = 0,008</td>
                </tr>
                <tr>
                  <td>Septo interventricular, mm</td>
                  <td align="center">10,1 &#177; 1,2</td>
                  <td align="center">10,1 &#177; 1,36</td>
                  <td align="center">p = 0,726</td>
                </tr>
                <tr>
                  <td>Parede posterior, mm</td>
                  <td align="center">9,8 &#177; 1,12</td>
                  <td align="center">9,9 &#177; 1,26</td>
                  <td align="center">p = 0,761</td>
                </tr>
                <tr>
                  <td>Mass VE, g</td>
                  <td align="center">181,5 &#177; 44,2</td>
                  <td align="center">198,7 &#177; 49,3</td>
                  <td align="center">p = 0,019</td>
                </tr>
                <tr>
                  <td>&#205;ndice de massa VE, g/m<sup>2</sup></td>
                  <td align="center">94,3 &#177; 22,4</td>
                  <td align="center">109,4 &#177; 28,4</td>
                  <td align="center">p = 0,002</td>
                </tr>
                <tr>
                  <td>Espessura da gordura epic&#225;rdica (s&#237;stole), cm</td>
                  <td align="center">0,72 &#177; 0,17</td>
                  <td align="center">0,81 &#177; 0,12</td>
                  <td align="center">p &lt; 0,001</td>
                </tr>
                <tr>
                  <td>Espessura da gordura epic&#225;rdica (di&#225;stole), cm</td>
                  <td align="center">0,46 &#177; 0,13</td>
                  <td align="center">0,54 &#177; 0,10</td>
                  <td align="center">p &lt; 0,001</td>
                </tr>
                <tr>
                  <td>PSAP, mmHg</td>
                  <td align="center">25,1 &#177; 7,5</td>
                  <td align="center">30,7 &#177; 8,7</td>
                  <td align="center">p &lt; 0,001</td>
                </tr>
                <tr>
                  <td>TAPSE, mm</td>
                  <td align="center">20,9 &#177; 4,1</td>
                  <td align="center">19,4 &#177; 3,6</td>
                  <td align="center">p = 0,017</td>
                </tr>
                <tr>
                  <td>Fra&#231;&#227;o de eje&#231;&#227;o VD, %</td>
                  <td align="center">53,1 &#177; 5,3</td>
                  <td align="center">50,1 &#177; 5,4</td>
                  <td align="center">p = 0,001</td>
                </tr>
                <tr>
                  <td>&#205;ndice Tei</td>
                  <td align="center">0,35 &#177; 0,09</td>
                  <td align="center">0,44 &#177; 0,11</td>
                  <td align="center">p &lt; 0,001</td>
                </tr>
                <tr>
                  <td>Escore SYNTAX</td>
                  <td align="center">20,6 &#177; 10,1</td>
                  <td align="center">21,2 &#177; 9,9</td>
                  <td align="center">p = 0,625</td>
                </tr>
                <tr>
                  <td>Les&#227;o na DAE, n (%)</td>
                  <td align="center">29 (41,4%)</td>
                  <td align="center">35 (38,0%)</td>
                  <td align="center">p = 0,744</td>
                </tr>
                <tr>
                  <td>Les&#227;o na Cx, n (%)</td>
                  <td align="center">17 (24,3%)</td>
                  <td align="center">16 (17,4%)</td>
                  <td align="center">p = 0,280</td>
                </tr>
                <tr>
                  <td>Les&#227;o na CD, n (%)</td>
                  <td align="center">24 (34,3%)</td>
                  <td align="center">41 (44,6%)</td>
                  <td align="center">p = 0,149</td>
                </tr>
                <tr>
                  <td>Mortalidade, n (%)</td>
                  <td align="center">3 (4,3%)</td>
                  <td align="center">13 (14,1%)</td>
                  <td align="center">p = 0,037</td>
                </tr>
                <tr>
                  <td>Perman&#234;ncia em UTI, dias</td>
                  <td align="center">3,3 &#177; 1,2</td>
                  <td align="center">4,3 &#177; 2,9</td>
                  <td align="center">p = 0,019</td>
                </tr>
                <tr>
                  <td>Total de hospitaliza&#231;&#227;o, dias</td>
                  <td align="center">5,6 &#177; 2,5</td>
                  <td align="center">6,9 &#177; 3,8</td>
                  <td align="center">p = 0,020</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN4">
                <p>Dados apresentados como m&#233;dia &#177; DP ou n&#250;mero (porcentagem)</p>
                <p>*Testes do qui-quadrado e t de amostras independentes</p>
                <p>VE: ventr&#237;culo esquerdo; VD: ventr&#237;culo direito; Cx: art&#233;ria circunflexa; HDL: lipoprote&#237;na de alta densidade; DAE: art&#233;ria descendente anterior esquerda; LDL: lipoprote&#237;na de baixa densidade; CD: art&#233;ria coron&#225;ria direita; PSAP: press&#227;o sist&#243;lica da art&#233;ria pulmonar; TAPSE: excurs&#227;o sist&#243;lica do plano anular tric&#250;spide; UTI: unidade de terapia intensiva.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Achados laboratoriais</title>
          <p>A avalia&#231;&#227;o de dados laboratoriais n&#227;o revelou diferen&#231;a entre a m&#233;dia dos valores de glicemia p&#243;s-prandial, HDL-colesterol, triglicer&#237;deos e cTn-I. As m&#233;dias dos valores de colesterol total (204,2 &#177; 55,9 vs. 185,7 &#177; 44,9 mg/dL, p = 0,022), LDL-colesterol (148,5 &#177; 43,9 vs. 133,1 &#177; 37,9 mg/dL, p = 0,019), prote&#237;na C reativa (2,68 &#177; 4,38 vs. 1,63 &#177; 3,4 mg/L, p = 0,013) e creatinina (1,18 &#177; 0,57 vs. 0,84 &#177; 0,20 mg/dL, p &lt; 0,001) foram maiores no grupo SG-A do que no grupo SG-BM (<xref ref-type="table" rid="t4">Tabela 1</xref>). </p>
        </sec>
        <sec>
          <title>Ecocardiografia e angiografia coronariana</title>
          <p>Os grupos n&#227;o diferiram quanto a septo interventricular e espessura da parede posterior. A FE foi mais baixa no grupo SG-A (43,3% &#177; 10,5 vs. 47,8% &#177; 10,2, p = 0,008). A EGE no final da s&#237;stole (0,81 &#177; 0,12 vs. 0,72 &#177; 0,17 cm, p &lt; 0,001), a EGE no final da di&#225;stole (0,54 &#177; 0,10 vs. 0,46 &#177; 0,13 cm, p &lt; 0,001) e a press&#227;o sist&#243;lica da art&#233;ria pulmonar (PSAP) (30,7 &#177; 8,7 vs. 25,1 &#177; 7,5 mmHg, p &lt; 0,001) foram mais altas no grupo SG-A. A FEVD, um dos indicadores da fun&#231;&#227;o sist&#243;lica do VD (50,1% &#177; 5,4 vs. 53,1% &#177; 5,3, p = 0,001), e a TAPSE (19,4 &#177; 3,6 vs. 20,9 &#177; 4,1, p = 0,017) foram mais baixas no grupo SG-A do que no grupo SG-BM (<xref ref-type="table" rid="t4">Tabela 1</xref>). O &#237;ndice Tei foi significativamente mais alto no grupo SG-A (0,48 &#177; 0,09 vs. 0,39 &#177; 0,08, p &lt; 0,001).</p>
          <p>Os angiogramas n&#227;o mostraram diferen&#231;a significativa entre os envolvimentos das art&#233;rias descendente anterior esquerda (DAE), circunflexa (Cx) e coron&#225;ria direita (CD) (<xref ref-type="table" rid="t4">Tabela 1</xref>). </p>
        </sec>
        <sec>
          <title>Correla&#231;&#227;o e an&#225;lise ROC</title>
          <p>Com base no SG intra-hospitalar, realizou-se a an&#225;lise ROC para calcular a EGE para predi&#231;&#227;o dos pacientes de alto risco. O valor de corte da EGE no final da s&#237;stole para o grupo SG-A foi de 0,765 cm (AUC: 0,699; IC 95%: 0,613-0,785; sensibilidade, 67%; especificidade, 64%) e o valor de corte da EGE no final da di&#225;stole foi de 0,468 cm para o grupo SG-A (AUC: 0,709; IC 95%: 0,621-0,797; sensibilidade, 68%; especificidade, 72%) (<xref ref-type="table" rid="t5">Tabela 2</xref>, <xref ref-type="fig" rid="f2">Figura 1</xref>).</p>
          <table-wrap id="t5">
            <label>Tabela 2</label>
            <caption>
              <title>De acordo com o escore GRACE intra-hospitalar (SG), realizou-se an&#225;lise <italic>receiver operating characteristic</italic> (ROC) para calcular a espessura da gordura epic&#225;rdica (EGE) para predi&#231;&#227;o de pacientes de alto risco</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th>
									</th>
                  <th align="center">
                    <bold>Corte (cm)</bold>
                  </th>
                  <th align="center">
                    <bold>Sensibilidade</bold>
                  </th>
                  <th align="center">
                    <bold>Especificidade</bold>
                  </th>
                  <th align="center">
                    <bold>AUC</bold>
                  </th>
                  <th align="center">
                    <bold>Intervalo de confian&#231;a 95%</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>EGE final da s&#237;stole / SG</td>
                  <td align="center">0,765</td>
                  <td align="center">67%</td>
                  <td align="center">64%</td>
                  <td align="center">0,699</td>
                  <td align="center">0,613-0,785</td>
                </tr>
                <tr>
                  <td>EGE final da di&#225;stole / SG</td>
                  <td align="center">0,468</td>
                  <td align="center">68%</td>
                  <td align="center">72%</td>
                  <td align="center">0,709</td>
                  <td align="center">0,621-0,797</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN5">
                <p>AUC (Area Under the Curve): &#225;rea sob a curva.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>
            <fig id="f2">
              <label>Figura 1</label>
              <caption>
                <title>Curva receiver operating characteristic (ROC). O ponto de corte da espessura da gordura epic&#225;rdica ao final da s&#237;stole para o grupo SG-A foi calculado em 0,765 cm (AUC: 0,699; IC 95%: 0,613-0,785; sensibilidade, 67%; especificidade, 64%). O ponto de corte da espessura da gordura epic&#225;rdica ao final da di&#225;stole para o grupo SG-A foi calculado em 0,468 cm (AUC: 0,709; IC 95%: 0,621-0,797; sensibilidade, 68%; especificidade, 72%). [AUC (area under the curve): &#225;rea sob a curva; IC: intervalo de confian&#231;a; SG-A: escore GRACE alto)</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-106-03-0194-60024-gf01-pt.jpg"/></fig>
          </p>
          <p>O coeficiente de correla&#231;&#227;o (r) do SG intra-hospitalar e a EGE no final da s&#237;stole foi de 0.387, enquanto o coeficiente de correla&#231;&#227;o (r) do SG intra-hospitalar e a EGE no final da di&#225;stole foi de 0,438 (<xref ref-type="table" rid="t6">Tabela 3</xref>).</p>
          <table-wrap id="t6">
            <label>Tabela 3</label>
            <caption>
              <title>Tabela de correla&#231;&#227;o para o escore GRACE intra-hospitalar (SG), escore SYNTAX e medidas de espessura da gordura epic&#225;rdica (EGE)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th>
									</th>
                  <th align="center">
                    <bold>Coeficiente de correla&#231;&#227;o (r)</bold>
                  </th>
                  <th align="center">
                    <bold>Valor de p</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>EGE final da s&#237;stole - SG</td>
                  <td align="center">r = 0,387</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td>EGE final da di&#225;stole - SG</td>
                  <td align="center">r = 0,438</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td>EGE final da s&#237;stole - escore SYNTAX</td>
                  <td align="center">r = 0,285</td>
                  <td align="center">0,009</td>
                </tr>
                <tr>
                  <td>EGE final da di&#225;stole - escore SYNTAX</td>
                  <td align="center">r = 0,292</td>
                  <td align="center">0,002</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN6">
                <p>An&#225;lise de correla&#231;&#227;o de Pearson</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Este estudo visou a mostrar a rela&#231;&#227;o entre o SG e a EGE de pacientes admitidos no nosso centro com o diagn&#243;stico de IMSSST. Este estudo demonstrou que a EGE acha-se associada com SG aumentado, e a an&#225;lise estat&#237;stica sugere que seria mais conveniente medir a EGE ao final da di&#225;stole.</p>
        <p>O sistema SG foi inicialmente usado para a avalia&#231;&#227;o progn&#243;stica de pacientes com SCA ap&#243;s o estudo multinacional <italic>Global Registry of Acute Coronary Events</italic> (GRACE).<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref> A detec&#231;&#227;o de um alto SG est&#225; associada com mau progn&#243;stico. Atualmente, as diretrizes de SCA recomendam seu uso para avalia&#231;&#227;o de risco. As diretrizes para diagn&#243;stico e tratamento de SCA da AHA e da ESC fornecem sugest&#245;es de como interpretar o SG. De acordo com essas recomenda&#231;&#245;es, um SG intra-hospitalar &gt; 140 indica alta morbimortalidade. Tais diretrizes recomendam revasculariza&#231;&#227;o precoce para pacientes de alto risco.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref> O nosso estudo identificou uma alta taxa de mortalidade (p = 0,001) no grupo SG-A com SG &gt; 140. Al&#233;m da taxa de mortalidade, os par&#226;metros ecocardiogr&#225;ficos ca&#237;ram no grupo SG-A. Os valores de FEVE do grupo SG-A foram mais baixos do que aqueles do grupo SG-BM. A FEVD e a TAPSE, marcadores da fun&#231;&#227;o sist&#243;lica do VD, mostraram-se reduzidas no grupo SG-A. O &#237;ndice Tei e a PSAP mostraram-se aumentadas no grupo SG-A.</p>
        <p>A gordura epic&#225;rdica &#233; um tipo de tecido adiposo visceral que se estende ao longo das art&#233;rias coron&#225;rias nos sulcos atrioventricular e interventricular. O mioc&#225;rdio e o tecido adiposo epic&#225;rdico encontram-se em contato direto, sendo o suprimento sangu&#237;neo para esses tecidos fornecido pelo mesmo sistema coronariano.<xref ref-type="bibr" rid="B17">17</xref> Assim, funcionando como um &#243;rg&#227;o end&#243;crino, o tecido adiposo epic&#225;rdico pode afetar direta e indiretamente as art&#233;rias coron&#225;rias e as estruturas card&#237;acas. O tecido adiposo epic&#225;rdico pode produzir v&#225;rias citocinas que estimulam angiog&#234;nese, inflama&#231;&#227;o, estresse oxidativo e aterosclerose. V&#225;rios estudos cl&#237;nicos recentes foram realizados para investigar a rela&#231;&#227;o entre EGE e doen&#231;as cardiovasculares. Como resultado desses estudos, uma EGE aumentada foi associada com um aumento do risco de doen&#231;a cardiovascular.<xref ref-type="bibr" rid="B5">5</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref><sup>-</sup><xref ref-type="bibr" rid="B22">22</xref> A EGE acha-se aumentada nos pacientes com inflama&#231;&#227;o, idade avan&#231;ada, obesidade, hipercolesterolemia, hipertens&#227;o, fibrila&#231;&#227;o atrial, diabetes mellitus e s&#237;ndrome metab&#243;lica.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B23">23</xref><sup>-</sup><xref ref-type="bibr" rid="B27">27</xref> No nosso estudo, n&#227;o houve diferen&#231;a significativa entre os grupos quanto a glicemia e &#237;ndice de massa corporal. O n&#250;mero de pacientes com diagn&#243;stico de s&#237;ndrome metab&#243;lica, diabetes e hipertens&#227;o foi similar entre os grupos (<xref ref-type="table" rid="t4">Tabela 1</xref>).</p>
        <p>H&#225; diversas recomenda&#231;&#245;es para a medida da EGE. Prefere-se usar a parede livre do VD como local de medida da EGE, cujo c&#225;lculo &#233; geralmente realizado no final da di&#225;stole.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref> Entretanto, algumas publica&#231;&#245;es sugerem que a EGE possa tamb&#233;m ser medida ao final da s&#237;stole.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> Recomenda-se a medida da EGE ao final da s&#237;stole durante o ciclo card&#237;aco devido &#224; compress&#227;o durante a di&#225;stole. No presente estudo, valores m&#233;dios de EGE foram obtidos empregando-se pelo menos tr&#234;s diferentes medidas para o final da s&#237;stole e o final da di&#225;stole, sendo os valores m&#233;dios de EGE mais altos no grupo SG-A do que no grupo SG-BM (p &lt; 0,001) (<xref ref-type="table" rid="t4">Tabela 1</xref>). Observou-se correla&#231;&#227;o entre o SG intra-hospitalar e a EGE (SG intra-hospitalar e EGE no final da s&#237;stole, r = 0,387; final da di&#225;stole, r = 0,438). As an&#225;lises ROC demonstraram que a EGE ao final da di&#225;stole foi melhor preditora de alto SG do que a EGE ao final da s&#237;stole (<xref ref-type="table" rid="t5">Tabela 2</xref>, <xref ref-type="fig" rid="f2">Figura 1</xref>).</p>
        <p>Limita&#231;&#245;es do estudo</p>
        <p>A principal limita&#231;&#227;o do presente estudo &#233; o relativamente pequeno tamanho da amostra. Tamb&#233;m, a ecocardiografia &#233; menos precisa do que as demais t&#233;cnicas radiol&#243;gicas para a avalia&#231;&#227;o do tecido adiposo epic&#225;rdico, embora uma boa correla&#231;&#227;o com a RNM tenha sido observada. Ainda, relatou-se uma correla&#231;&#227;o moderada com o volume de gordura epic&#225;rdica avaliado com RNM cardiovascular. A despeito do baixo n&#237;vel de acur&#225;cia, a medida da EGE atrav&#233;s de ecocardiografia &#233; mais vi&#225;vel do atrav&#233;s de RNM.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#245;es</title>
        <p>Estudos pr&#233;vios mostraram EGE aumentada em v&#225;rias condi&#231;&#245;es e patologias que podem dificultar as fun&#231;&#245;es card&#237;acas. No nosso estudo, as taxas de mortalidade e morbidade estavam aumentadas no grupo SG-A. O SG mostrou uma correla&#231;&#227;o positiva com EGE ao final da s&#237;stole e EGE ao final da di&#225;stole. As avalia&#231;&#245;es estat&#237;sticas demonstraram uma melhor correla&#231;&#227;o entre SG e EGE ao final da di&#225;stole do que EGE ao final da s&#237;stole.</p>
        <p>Concluindo, o c&#225;lculo da EGE ao final da di&#225;stole pode fornecer informa&#231;&#227;o &#250;til em pacientes com alto SG durante a avalia&#231;&#227;o ecocardiogr&#225;fica de IMSSST.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s&#8209;gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
