Original Article
Metformin monotherapy significantly decreases epicardial adipose tissue thickness in newly diagnosed type 2 diabetes patients
A monoterapia com metformina diminiu significativamente a espessura do tecido adiposo epicárdico nos doentes recentemente diagnosticados com diabetes tipo 2
Lido
4912
Vezesque se leu este artigo
1708
Total PDF
3204
Total HTML
Compartilhar estatísticas
array:26 [ "pii" => "S0870255118301641" "issn" => "08702551" "doi" => "10.1016/j.repc.2018.08.010" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1404" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2019;38:419-23" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 632 "formatos" => array:3 [ "EPUB" => 52 "HTML" => 405 "PDF" => 175 ] ] "Traduccion" => array:1 [ "en" => array:20 [ "pii" => "S2174204919301758" "issn" => "21742049" "doi" => "10.1016/j.repce.2019.07.001" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1405" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2019;38:425-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 227 "formatos" => array:3 [ "EPUB" => 14 "HTML" => 166 "PDF" => 47 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Epicardial adipose tissue: An important therapeutic target" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "425" "paginaFinal" => "426" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Tecido adiposo epicárdico: um alvo terapêutico importante" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cristina M. Sena" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Cristina M." "apellidos" => "Sena" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255119304275" "doi" => "10.1016/j.repc.2019.07.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255119304275?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204919301758?idApp=UINPBA00004E" "url" => "/21742049/0000003800000006/v1_201909140841/S2174204919301758/v1_201909140841/en/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S0870255119304275" "issn" => "08702551" "doi" => "10.1016/j.repc.2019.07.001" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1405" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2019;38:425-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 676 "formatos" => array:3 [ "EPUB" => 61 "HTML" => 479 "PDF" => 136 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Epicardial adipose tissue: An important therapeutic target" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "425" "paginaFinal" => "426" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Tecido adiposo epicárdico: um alvo terapêutico importante" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cristina M. Sena" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Cristina M." "apellidos" => "Sena" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204919301758" "doi" => "10.1016/j.repce.2019.07.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204919301758?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255119304275?idApp=UINPBA00004E" "url" => "/08702551/0000003800000006/v3_201911281004/S0870255119304275/v3_201911281004/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S087025511930321X" "issn" => "08702551" "doi" => "10.1016/j.repc.2019.05.006" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1388" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2019;38:417-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 747 "formatos" => array:3 [ "EPUB" => 62 "HTML" => 543 "PDF" => 142 ] ] "pt" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Comentário editorial</span>" "titulo" => "E a clínica continua soberana" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "417" "paginaFinal" => "418" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Clinical findings remain paramount" ] ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Gláucia Maria Moraes de Oliveira" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Gláucia Maria Moraes de" "apellidos" => "Oliveira" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204919301989" "doi" => "10.1016/j.repce.2019.07.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204919301989?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S087025511930321X?idApp=UINPBA00004E" "url" => "/08702551/0000003800000006/v3_201911281004/S087025511930321X/v3_201911281004/pt/main.assets" ] "asociados" => array:1 [ 0 => array:20 [ "pii" => "S0870255119304275" "issn" => "08702551" "doi" => "10.1016/j.repc.2019.07.001" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1405" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2019;38:425-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 676 "formatos" => array:3 [ "EPUB" => 61 "HTML" => 479 "PDF" => 136 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Epicardial adipose tissue: An important therapeutic target" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "425" "paginaFinal" => "426" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Tecido adiposo epicárdico: um alvo terapêutico importante" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cristina M. Sena" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Cristina M." "apellidos" => "Sena" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204919301758" "doi" => "10.1016/j.repce.2019.07.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204919301758?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255119304275?idApp=UINPBA00004E" "url" => "/08702551/0000003800000006/v3_201911281004/S0870255119304275/v3_201911281004/en/main.assets" ] ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Metformin monotherapy significantly decreases epicardial adipose tissue thickness in newly diagnosed type 2 diabetes patients" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "419" "paginaFinal" => "423" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Murat Ziyrek, Serkan Kahraman, Emrah Ozdemir, Ali Dogan" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Murat" "apellidos" => "Ziyrek" "email" => array:1 [ 0 => "muziyrek@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Serkan" "apellidos" => "Kahraman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Emrah" "apellidos" => "Ozdemir" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Ali" "apellidos" => "Dogan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Silivri State Hospital, Department of Cardiology, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Yeniyüzyıl University, Faculty of Medicine, Department of Cardiology, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "A monoterapia com metformina diminiu significativamente a espessura do tecido adiposo epicárdico nos doentes recentemente diagnosticados com diabetes tipo 2" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 905 "Ancho" => 2175 "Tamanyo" => 203871 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Measurement of EAT thickness. (A) Parasternal long-axis view; (B) parasternal short-axis view. Ao: aorta; EAT: epicardial adipose tissue; LV: left ventricle; RV: right ventricle.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Visceral adipose tissue (VAT), anatomically located around certain organs, is now accepted as an endocrine organ which secretes various adipokines that influence both nearby and distant tissues. Imbalance between pro- and anti-inflammatory adipokines secreted from VAT contributes to the pathogenesis of certain cardiovascular and metabolic disorders, including insulin resistance.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> Epicardial adipose tissue (EAT), an organ-specific VAT, is mainly found in the atrioventricular and interventricular grooves and along the major branches of the coronary arteries, and to a lesser extent around the atria, over the free wall of the right ventricle and over the apex of the left ventricle.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">2</span></a> Evidence is accumulating that bioactive molecules secreted by EAT can directly affect intima-media thickness and regulate vasomotor function.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a> Furthermore, there is emerging evidence that EAT has a direct association with coronary atherosclerosis.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> In view of the putative proatherogenic effect of EAT, several clinical trials have shown a positive correlation between EAT thickness and coronary atherosclerosis.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">5–7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Although its exact mechanism of action is unknown, metformin is regarded as the gold standard treatment for type 2 diabetes.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> Beside its glucose-lowering effect, metformin also has a favorable effect on body weight, primarily due to reduction of VAT.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> In this study, we investigated the effects of metformin on EAT thickness and body mass index (BMI) in type 2 diabetes patients.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Study population</span><p id="par0015" class="elsevierStylePara elsevierViewall">In this prospective observational study, we analyzed consecutive patients referred to the internal medicine outpatient clinic between September 1, 2015 and May 31, 2016. Patients with BMI <20 or >35 kg/m<span class="elsevierStyleSup">2</span> or poor echocardiographic window were excluded. A total of 47 newly diagnosed type 2 diabetes patients prescribed metformin monotherapy were selected. Clinical and demographic features of the selected patients were recorded. All patients were informed about the study and written consent was obtained. The study was approved by the local ethics committee.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study protocol</span><p id="par0020" class="elsevierStylePara elsevierViewall">Before initiation of metformin monotherapy, the BMI of all recruited patients was calculated (BMI0) and all underwent transthoracic echocardiography to assess EAT thickness (EAT0). Metformin 1000 mg twice daily was prescribed to all participants. After three months of metformin monotherapy, BMI was recalculated (BMI3) and transthoracic echocardiographic studies were repeated to measure EAT thickness (EAT3), and the resulting data were statistically analyzed.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Measurement of epicardial adipose tissue thickness</span><p id="par0025" class="elsevierStylePara elsevierViewall">All included patients underwent detailed two-dimensional (2D), M-mode, Doppler, and tissue Doppler transthoracic echocardiography using standard techniques before beginning metformin monotherapy and after three months of treatment. The echocardiograms were performed by two experienced cardiologists who were blinded to the subjects’ clinical and demographic data. Each subject underwent 2D-guided M-mode transthoracic echocardiography using commercially available equipment (Aplio 500, Toshiba, Irvine, CA). Standard parasternal and apical views were obtained in left lateral decubitus position. EAT was visualized as echo-free space between the outer wall of the myocardium and the visceral layer of the pericardium (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). EAT thickness was measured perpendicularly on the free wall of the right ventricle during three cardiac cycles at end-diastole. Parasternal long- and short-axis views provided the most accurate measurement of EAT in the right ventricle, with optimal cursor beam orientation in each view. Maximum EAT thickness was measured at the point on the free wall of the right ventricle along the midline of the ultrasound beam perpendicular to the aortic annulus, used as an anatomic landmark for this view. For midventricular parasternal short-axis assessment, maximum EAT thickness was measured on the right ventricular free wall along the midline of the ultrasound beam, perpendicular to the ventricular septum at midchordal and tip of the papillary muscle level, as anatomic landmarks. The mean values from three cardiac cycles in each echocardiographic view were analyzed.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">The statistical analysis was conducted using SPSS software, version 16.0 (IBM, Chicago, IL). Data were expressed as mean ± standard deviation for continuous variables and as counts and percentage for categorical variables. The Student's t test was used to compare continuous variables, while the chi-square and Fisher's exact tests were used to compare categorical variables. Correlations of continuous variables were assessed using Pearson correlation analysis. Values 0-0.3 indicated weak, 0.3-0.7 indicated intermediate, and 0.7-1.0 indicated strong correlation. A p value <0.05 was considered statistically significant.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Seven patients were excluded due to metformin intolerance during the follow-up period, and so a total of 40 patients were analyzed. Of the study population, 23 (57.5%) were male and mean age was 48.6±1.99 years. Fourteen patients (35%) had hypertension, 12 (30%) had hyperlipidemia and 13 (32.5%) were smokers. Mean fasting blood glucose was 280.38±14.88 mg/dl before beginning metformin monotherapy, falling to 129.01±17.00 mg/dl after three months of therapy.</p><p id="par0040" class="elsevierStylePara elsevierViewall">EAT thickness was significantly decreased after three months of metformin monotherapy (EAT0= 5.07±1.33 mm vs. EAT3=4.76±1.32 mm; p<0.001) (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Furthermore, BMI was also significantly decreased after three months of metformin monotherapy (BMI0=28.27±2.71 vs. BMI3=27.29±2.10; p<0.0001) (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">We also analyzed the correlation between the decrease in EAT (formulated as EAT0 - EAT3) and mean fasting blood glucose level before beginning metformin monotherapy and BMI0. A statistically non-significant positive correlation was found between decrease in EAT and mean fasting blood glucose before beginning therapy (r=0.19; p=0.056) and BMI0 (r=0.17; p=0.053).</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">In this study we demonstrated that metformin monotherapy significantly decreases EAT thickness and BMI as early as the third month of therapy.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Because of its vital endocrine function and close anatomical relation to the coronary arteries, many studies have set out to determine the effects of EAT on cardiovascular disease. Mahabadi et al. showed the existence of a relation between cardiovascular risk factors, myocardial infarction and EAT thickness,<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a> while Cavalcante et al. found a significant association between subclinical coronary atherosclerosis, metabolic syndrome, diastolic dysfunction and EAT thickness.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> In a recently published study, Abazid et al. also concluded that higher EAT volume is associated with greater coronary artery calcification,<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> and Wu et al. showed that EAT thickness is positively correlated with obstructive coronary artery disease (CAD).<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Although the exact mechanism is unknown, several hypotheses have been put forward to explain this relation. EAT is a metabolically active fat depot which is rich in proinflammatory and proatherogenic cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a> In a recent study, Vrselja et al. demonstrated that TNF-α levels were increased in CAD patients.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">15</span></a> Furthermore, Eiras et al. postulated that the extent of CAD was associated with the expression of IL-6 mRNA in EAT.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">16</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">EAT shares the same embryologic origin as mesenteric and omental fat.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">17,18</span></a> They all encase viscera in close contact, with no fascial barrier.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">19</span></a> Hence it has been suggested that EAT may have endocrine and paracrine effects on the adjacent coronary arterial wall that could result in atherosclerotic plaque development.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">20–22</span></a> These findings highlight the potential role of increased EAT thickness in atherosclerosis. It could therefore be postulated that decreased EAT would produce less proinflammatory and proatherogenic cytokines and be less likely to cause atherosclerosis.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Metformin is now accepted as the first-line drug for use as monotherapy in type 2 diabetes patients. It is thought to affect certain aspects of the body's metabolism. It inhibits hepatic gluconeogenesis, augments peripheral glucose uptake, and reduces insulin demand.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> Various studies have also investigated the effect of metformin on body weight and visceral adipose tissue. In a recent study, Alfaras et al. showed in mice that metformin significantly reduces body weight within the first weeks of treatment, without affecting food consumption or energy expenditure.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">23</span></a> Yanovski et al. showed that metformin significantly reduced body weight in children with insulin resistance,<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">24</span></a> while Tokubuchi et al. demonstrated that metformin treatment caused significant reductions in visceral fat mass, probably through a potential shift of fuel resource into fat oxidation and upregulation of thermogenesis.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Although there have been many studies on the effects of metformin on body weight and VAT, there is hardly any data about its effect on EAT. In our study, we showed that metformin significantly reduces BMI and EAT thickness. Magnetic resonance imaging (MRI) and computed tomography (CT) are the gold-standard techniques for quantifying EAT volume. Due to the difficulty in standardizing localization of the measurement site, reference values for EAT assessed by CT are uncertain.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a> Iacobellis et al. were the first to propose that transthoracic echocardiography could be an easy and reliable imaging method for EAT prediction.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a> MRI and transthoracic echocardiography provide comparable results for detection of EAT volume.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a> Hence measurement of EAT by transthoracic echocardiography is practical, cost-effective, safe, rapid, and well correlated to gold-standard techniques.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Study limitations</span><p id="par0085" class="elsevierStylePara elsevierViewall">As this is the first study to investigate the effect of metformin on EAT thickness, it is subject to some limitations, the main ones being its relatively small sample size and the lack of data on inflammatory markers. Due to financial constraints we were unable to analyze the possible effects of inflammation on the results. Larger-scale and more detailed studies should be designed to clarify the exact mechanisms underlying the favorable effects of metformin on EAT thickness and BMI.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusion</span><p id="par0090" class="elsevierStylePara elsevierViewall">To the best of our knowledge, our study demonstrates for the first time in the literature that metformin significantly reduces EAT thickness in newly diagnosed type 2 diabetes. Because EAT volume is closely related to atherosclerosis, it could be concluded that EAT is a modifiable risk factor for atherosclerosis and that metformin could significantly reduce the frequency of coronary atherosclerosis. Metformin could even become the aspirin of the 21st century. Further studies on a larger scale are needed to support these findings.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1269315" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1174830" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1269316" "titulo" => "Resumo" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1174831" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study protocol" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Measurement of epicardial adipose tissue thickness" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Study limitations" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-03-04" "fechaAceptado" => "2018-08-01" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1174830" "palabras" => array:4 [ 0 => "Adipose tissue" 1 => "Coronary atherosclerosis" 2 => "Type 2 diabetes" 3 => "Metformin" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec1174831" "palabras" => array:4 [ 0 => "Tecido adiposo" 1 => "Aterosclerose coronária" 2 => "Diabetes tipo 2" 3 => "Metformina" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Imbalance between pro- and anti-inflammatory cytokines secreted from visceral adipose tissue (VAT) contributes to the pathogenesis of certain cardiovascular and metabolic disorders, including insulin resistance. Epicardial adipose tissue (EAT) is a form of VAT mainly concentrated along the coronary arteries. It has been shown in various studies that EAT thickness is positively correlated with cardiovascular disease. Due to its high worldwide prevalence, prevention and management of type 2 diabetes (T2D) has become a major public health challenge. Metformin, the most widely prescribed drug to treat T2D, has favorable effects on VAT and body weight. As metformin decreases VAT mass, in this prospective study we analyzed the possible positive effect of metformin on EAT mass, which is organ-specific VAT, and body mass index (BMI).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Subjects were selected from patients admitted to the internal medicine outpatient clinic. Newly diagnosed T2D patients treated with metformin monotherapy were analyzed and 40 patients were included. EAT thickness in the included patients was measured echocardiographically. BMI and EAT thickness were analyzed at the beginning (BMI0 and EAT0) and after three months of metformin monotherapy (BMI3 and EAT3).</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">There was a statistically significant decrease in EAT thickness after three months of metformin monotherapy (EAT0=5.07±1.33 mm vs. EAT3=4.76±1.32 mm; p<0.001). Furthermore, BMI was also significantly decreased (BMI0=28.27±2.71 vs. BMI3=27.29±2.10; p<0.0001).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In this study we show that metformin monotherapy significantly decreases EAT thickness and BMI in T2D patients. This suggests that metformin could reduce the frequency of coronary atherosclerosis.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">O desequilíbrio entre as citocinas pro e anti-inflamatórias segregadas pelo tecido adiposo visceral (TAV) contribui para a patogénese de certas doenças cardiovasculares e metabólicas, incluindo a resistência à insulina. O tecido adiposo epicárdico (EAT) é o TAV, concentrado principalmente ao longo das artérias coronárias. É previamente demonstrado em vários estudos que a espessura do EAT está positivamente correlacionada com a frequência de doença cardiovascular. Devido à alta prevalência mundial, a prevenção e tratamento da diabetes <span class="elsevierStyleItalic">mellitus</span> tipo 2 (DM2) tornou-se um grande desafio para a saúde pública. A metformina, o medicamento mais amplamente prescrito para o tratamento da DM2, tem efeitos favoráveis no TAV e no peso corporal. Como a metformina diminui a massa do TAV, neste estudo prospetivo, analisamos o possível efeito positivo da metformina na massa do EAT, que é o TAV do órgão e o índice de massa corporal.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os indivíduos foram selecionados dos doentes admitidos no ambulatório de medicina interna. Doentes recém-diagnosticados com DM2 tratados com metformina em monoterapia foram investigados. Foram incluídos 40 doentes. A espessura do EAT dos doentes incluídos foi medida por ecocardiografia. A espessura do IMC e do EAT no início e três meses após a monoterapia com metformina foi analisada.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Houve redução estatisticamente significativa na espessura do EAT após três meses de monoterapêutica com metformina (EAT0=5,07±1,33 mm <span class="elsevierStyleItalic">versus</span> EAT3=4,76±1,32 mm; p<0,001). Além disso, o IMC também diminuiu significativamente (IMC0=28,27±2,71 <span class="elsevierStyleItalic">versus</span> IMC3=27,29±2,10; p<0,0001).</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Conclusões Neste estudo, verificámos que a metformina em monoterapia diminui significativamente a espessura do EAT e o IMC nos doentes com DM2, pelo que se pode concluir que a metformina pode reduzir a frequência de aterosclerose coronária.</p></span>" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">This work was presented as an oral presentation at the 32nd Turkish National Cardiology Congress (October 20-23, 2016).</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 905 "Ancho" => 2175 "Tamanyo" => 203871 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Measurement of EAT thickness. (A) Parasternal long-axis view; (B) parasternal short-axis view. Ao: aorta; EAT: epicardial adipose tissue; LV: left ventricle; RV: right ventricle.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1487 "Ancho" => 1500 "Tamanyo" => 60076 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Effect of metformin monotherapy on EAT thickness. EAT0: EAT thickness before initiation of metformin monotherapy; EAT3: EAT thickness after three months of metformin monotherapy; EAT: epicardial adipose tissue.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1553 "Ancho" => 1500 "Tamanyo" => 62064 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Effect of metformin monotherapy on BMI. BMI0: BMI before initiation of metformin monotherapy; BMI3: BMI after three months of metformin monotherapy; BMI: body mass index.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0150" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vasocrine signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.S. Yudkin" 1 => "E. Eringa" 2 => "C.D. Stehouwer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(05)66585-3" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2005" "volumen" => "365" "paginaInicial" => "1817" "paginaFinal" => "1820" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15910955" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0155" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Iacobellis" 1 => "D. Corradi" 2 => "A.M. Sharma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ncpcardio0319" "Revista" => array:6 [ "tituloSerie" => "Nat Clin Pract Cardiovasc Med" "fecha" => "2005" "volumen" => "2" "paginaInicial" => "536" "paginaFinal" => "543" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16186852" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0160" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human epicardial adipose tissue: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.S. Sacks" 1 => "J.N. Fain" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ahj.2007.03.019" "Revista" => array:6 [ "tituloSerie" => "Am Heart J" "fecha" => "2007" "volumen" => "153" "paginaInicial" => "907" "paginaFinal" => "917" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17540190" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0165" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of epicardial adipose tissue with coronary atherosclerosis is region-specific and independent of conventional risk factors and intra-abdominal adiposity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "T.D. Wang" 1 => "W.J. Lee" 2 => "F.Y. Shih" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.atherosclerosis.2010.07.055" "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis" "fecha" => "2010" "volumen" => "213" "paginaInicial" => "279" "paginaFinal" => "287" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20801451" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0170" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical significance of epicardial fat measured using cardiac multislice computed tomography" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Sarin" 1 => "C. Wenger" 2 => "A. Marwaha" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.amjcard.2008.04.058" "Revista" => array:6 [ "tituloSerie" => "Am J Cardiol" "fecha" => "2008" "volumen" => "102" "paginaInicial" => "767" "paginaFinal" => "771" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18774004" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0175" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association of pericardial fat with incident coronary heart disease: the Multi Ethnic Study of Atherosclerosis (MESA)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Ding" 1 => "F.C. Hsu" 2 => "T.B. Harris" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3945/ajcn.2008.27358" "Revista" => array:6 [ "tituloSerie" => "Am J Clin Nutr" "fecha" => "2009" "volumen" => "90" "paginaInicial" => "499" "paginaFinal" => "504" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19571212" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0180" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Subepicardial adipose tissue and the presence and severity of coronary artery disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "N. Chaowalit" 1 => "V.K. Somers" 2 => "P.A. Pellikka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.atherosclerosis.2005.08.004" "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis" "fecha" => "2006" "volumen" => "186" "paginaInicial" => "354" "paginaFinal" => "359" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16183065" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0185" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metformin – a new old drug" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.P. Wróbel" 1 => "B. Marek" 2 => "D. Kajdaniuk" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5603/EP.2017.0050" "Revista" => array:6 [ "tituloSerie" => "Endokrynol Pol" "fecha" => "2017" "volumen" => "68" "paginaInicial" => "482" "paginaFinal" => "496" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28819951" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0190" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Selective decrease in visceral fat is associated with weight loss during metformin treatment in African Americans with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R. Kurukulasuriya" 1 => "M.A. Banerji" 2 => "R. Chaiken" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Diabetes" "fecha" => "1999" "volumen" => "48" "paginaInicial" => "315" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0195" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.A. Mahabadi" 1 => "M.H. Berg" 2 => "N. Lehmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2012.11.062" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2013" "volumen" => "61" "paginaInicial" => "1388" "paginaFinal" => "1395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23433560" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0200" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of epicardial fat, hypertension, subclinical coronary artery disease, and metabolic syndrome with left ventricular diastolic dysfunction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.L. Cavalcante" 1 => "B.K. Tamarappoo" 2 => "R. Hachamovitch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.amjcard.2012.07.045" "Revista" => array:6 [ "tituloSerie" => "Am J Cardiol" "fecha" => "2012" "volumen" => "110" "paginaInicial" => "1793" "paginaFinal" => "1798" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22980968" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0205" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relation between epicardial fat and subclinical atherosclerosis in asymptomatic individuals" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.M. Abazid" 1 => "O.A. Smettei" 2 => "M.O. Kattea" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/RTI.0000000000000296" "Revista" => array:6 [ "tituloSerie" => "J Thorac Imaging" "fecha" => "2017" "volumen" => "32" "paginaInicial" => "378" "paginaFinal" => "382" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28817459" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0210" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The relation of location-specific epicardial adipose tissue thickness and obstructive coronary artery disease: systemic review and meta-analysis of observational studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F.Z. Wu" 1 => "K.J. Chou" 2 => "Y.L. Huang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2261-14-62" "Revista" => array:5 [ "tituloSerie" => "BMC Cardiovasc Disord" "fecha" => "2014" "volumen" => "14" "paginaInicial" => "62" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24884458" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0215" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of epicardial adipose tissue and high-risk plaque characteristics: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "N. Nerlekar" 1 => "A.J. Brown" 2 => "R.G. Muthalaly" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "J Am Heart Assoc" "fecha" => "2017" "volumen" => "6" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0220" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transcardial gradient of adiponectin, interleukin-6 and tumor necrosis factor-α in overweight coronary artery disease patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Z. Vrselja" 1 => "M. Šram" 2 => "D. Andrijevic" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cyto.2015.09.009" "Revista" => array:6 [ "tituloSerie" => "Cytokine" "fecha" => "2015" "volumen" => "76" "paginaInicial" => "321" "paginaFinal" => "327" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26385653" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0225" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extension of coronary artery disease is associated with increased IL-6 and decreased adiponectin gene expression in epicardial adipose tissue" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Eiras" 1 => "E. Teijeira-Fernández" 2 => "L.G. Shamagian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cyto.2008.05.006" "Revista" => array:6 [ "tituloSerie" => "Cytokine" "fecha" => "2008" "volumen" => "43" "paginaInicial" => "174" "paginaFinal" => "180" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18562207" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0230" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of pericardial fat and coronary high-risk lesions as determined by cardiac CT" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.L. Schlett" 1 => "M. Ferencik" 2 => "M.F. Kriegel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.atherosclerosis.2012.02.029" "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis" "fecha" => "2012" "volumen" => "222" "paginaInicial" => "129" "paginaFinal" => "134" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22417843" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0235" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relationship of epicardial fat volume to coronary plaque, severe coronary stenosis, and high-risk coronary plaque features assessed by coronary CT angiography" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R. Rajani" 1 => "H. Shmilovich" 2 => "R. Nakazato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcct.2013.02.003" "Revista" => array:6 [ "tituloSerie" => "J Cardiovasc Comput Tomogr" "fecha" => "2013" "volumen" => "7" "paginaInicial" => "125" "paginaFinal" => "132" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23622507" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0240" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.P. Fitzgibbons" 1 => "M.P. Czech" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/JAHA.113.000582" "Revista" => array:5 [ "tituloSerie" => "J Am Heart Assoc" "fecha" => "2014" "volumen" => "3" "paginaInicial" => "e000582" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24595191" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0245" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relationship between epicardial fat and quantitative coronary artery plaque progression: insights from computer tomography coronary angiography" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "P.J. Psaltis" 1 => "A.H. Talman" 2 => "K. Munnur" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10554-015-0762-3" "Revista" => array:6 [ "tituloSerie" => "Int J Cardiovasc Imaging" "fecha" => "2016" "volumen" => "32" "paginaInicial" => "317" "paginaFinal" => "328" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26335371" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0250" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Shimabukuro" 1 => "Y. Hirata" 2 => "M. Tabata" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/ATVBAHA.112.300829" "Revista" => array:6 [ "tituloSerie" => "Arterioscler Thromb Vasc Biol" "fecha" => "2013" "volumen" => "33" "paginaInicial" => "1077" "paginaFinal" => "1084" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23471228" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0255" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eccentric atherosclerotic plaques with positive remodelling have a pericardial distribution: a permissive role of epicardial fat? A three-dimensional intravascular ultrasound study of left anterior descending artery lesions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F. Prati" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0195-668x(02)00426-8" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2003" "volumen" => "24" "paginaInicial" => "329" "paginaFinal" => "336" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12581680" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0260" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Health benefits of late-onset metformin treatment every other week in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "I. Alfaras" 1 => "S.J. Mitchell" 2 => "H. Mora" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41514-017-0018-7" "Revista" => array:5 [ "tituloSerie" => "NPJ Aging Mech Dis" "fecha" => "2017" "volumen" => "3" "paginaInicial" => "16" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29167747" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0265" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.A. Yanovski" 1 => "J. Krakoff" 2 => "C.G. Salaita" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/db10-1185" "Revista" => array:6 [ "tituloSerie" => "Diabetes" "fecha" => "2011" "volumen" => "60" "paginaInicial" => "477" "paginaFinal" => "485" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21228310" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0270" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "I. Tokubuchi" 1 => "Y. Tajiri" 2 => "S. Iwata" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0171293" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2017" "volumen" => "12" "paginaInicial" => "e0171293" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28158227" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0275" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "P.M. Gorter" 1 => "A.M. De Vos" 2 => "Y. van der Graaf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.amjcard.2008.04.002" "Revista" => array:6 [ "tituloSerie" => "Am J Cardiol" "fecha" => "2008" "volumen" => "102" "paginaInicial" => "380" "paginaFinal" => "385" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18678291" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0280" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G. Iacobellis" 1 => "F. Assael" 2 => "M.C. Ribaudo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/oby.2003.45" "Revista" => array:6 [ "tituloSerie" => "Obes Res" "fecha" => "2003" "volumen" => "11" "paginaInicial" => "304" "paginaFinal" => "310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12582228" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0285" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pericardial rather than epicardial fat is a cardiometabolic risk marker: an MRI vs echo study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R. Sicari" 1 => "A.M. Sironi" 2 => "R. Petz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.echo.2011.06.013" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Echocardiogr" "fecha" => "2011" "volumen" => "24" "paginaInicial" => "1156" "paginaFinal" => "1162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21795020" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0290" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epicardial adipose tissue imaged by magnetic resonance imaging: an important risk marker of cardiovascular disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Kessels" 1 => "M.J. Cramer" 2 => "B. Veldhuis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/hrt.2005.074872" "Revista" => array:5 [ "tituloSerie" => "Heart" "fecha" => "2006" "volumen" => "92" "paginaInicial" => "962" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16775103" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000003800000006/v3_201911281004/S0870255118301641/v3_201911281004/en/main.assets" "Apartado" => array:4 [ "identificador" => "29261" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Artigos Originais" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000003800000006/v3_201911281004/S0870255118301641/v3_201911281004/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255118301641?idApp=UINPBA00004E" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 7 | 7 | 14 |
| 2024 Outubro | 61 | 45 | 106 |
| 2024 Setembro | 62 | 25 | 87 |
| 2024 Agosto | 74 | 33 | 107 |
| 2024 Julho | 64 | 35 | 99 |
| 2024 Junho | 56 | 28 | 84 |
| 2024 Maio | 76 | 25 | 101 |
| 2024 Abril | 64 | 37 | 101 |
| 2024 Maro | 70 | 24 | 94 |
| 2024 Fevereiro | 68 | 22 | 90 |
| 2024 Janeiro | 88 | 27 | 115 |
| 2023 Dezembro | 45 | 29 | 74 |
| 2023 Novembro | 67 | 37 | 104 |
| 2023 Outubro | 31 | 15 | 46 |
| 2023 Setembro | 39 | 19 | 58 |
| 2023 Agosto | 44 | 17 | 61 |
| 2023 Julho | 60 | 11 | 71 |
| 2023 Junho | 49 | 13 | 62 |
| 2023 Maio | 73 | 32 | 105 |
| 2023 Abril | 37 | 4 | 41 |
| 2023 Maro | 73 | 22 | 95 |
| 2023 Fevereiro | 50 | 15 | 65 |
| 2023 Janeiro | 39 | 13 | 52 |
| 2022 Dezembro | 76 | 19 | 95 |
| 2022 Novembro | 57 | 27 | 84 |
| 2022 Outubro | 76 | 26 | 102 |
| 2022 Setembro | 60 | 43 | 103 |
| 2022 Agosto | 51 | 33 | 84 |
| 2022 Julho | 53 | 38 | 91 |
| 2022 Junho | 49 | 43 | 92 |
| 2022 Maio | 47 | 30 | 77 |
| 2022 Abril | 52 | 34 | 86 |
| 2022 Maro | 67 | 50 | 117 |
| 2022 Fevereiro | 57 | 47 | 104 |
| 2022 Janeiro | 49 | 43 | 92 |
| 2021 Dezembro | 51 | 37 | 88 |
| 2021 Novembro | 48 | 50 | 98 |
| 2021 Outubro | 34 | 42 | 76 |
| 2021 Setembro | 37 | 37 | 74 |
| 2021 Agosto | 51 | 36 | 87 |
| 2021 Julho | 29 | 39 | 68 |
| 2021 Junho | 32 | 26 | 58 |
| 2021 Maio | 41 | 40 | 81 |
| 2021 Abril | 59 | 51 | 110 |
| 2021 Maro | 32 | 18 | 50 |
| 2021 Fevereiro | 42 | 20 | 62 |
| 2021 Janeiro | 36 | 23 | 59 |
| 2020 Dezembro | 42 | 18 | 60 |
| 2020 Novembro | 37 | 22 | 59 |
| 2020 Outubro | 33 | 18 | 51 |
| 2020 Setembro | 41 | 13 | 54 |
| 2020 Agosto | 39 | 9 | 48 |
| 2020 Julho | 14 | 10 | 24 |
| 2020 Junho | 30 | 15 | 45 |
| 2020 Maio | 19 | 10 | 29 |
| 2020 Abril | 18 | 9 | 27 |
| 2020 Maro | 27 | 13 | 40 |
| 2020 Fevereiro | 82 | 45 | 127 |
| 2020 Janeiro | 20 | 7 | 27 |
| 2019 Dezembro | 29 | 20 | 49 |
| 2019 Novembro | 56 | 17 | 73 |
| 2019 Outubro | 38 | 17 | 55 |
| 2019 Setembro | 107 | 35 | 142 |
| 2019 Agosto | 55 | 19 | 74 |
| 2019 Julho | 34 | 24 | 58 |
Mostrar tudo
