Correlations between osteoprotegerin serum levels and body composition parameters in patients with sleep apnea syndrome and the possible influence on cardiovascular risk
Read
8156
Timeswas read the article
2694
Total PDF
5462
Total HTML
Share statistics
array:20 [ "pii" => "X0873215915364922" "issn" => "08732159" "doi" => "10.1016/j.rppnen.2015.01.002" "estado" => "S300" "fechaPublicacion" => "2015-09-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2015;21:239-44" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4376 "formatos" => array:3 [ "EPUB" => 252 "HTML" => 3160 "PDF" => 964 ] ] "itemSiguiente" => array:16 [ "pii" => "X0873215915364930" "issn" => "08732159" "doi" => "10.1016/j.rppnen.2015.04.007" "estado" => "S300" "fechaPublicacion" => "2015-09-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2015;21:245-52" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4611 "formatos" => array:3 [ "EPUB" => 245 "HTML" => 3430 "PDF" => 936 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Different spontaneous breathing trials in patients with atrial fibrillation" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "245" "paginaFinal" => "252" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v21n05-90436493fig1.jpg" "Alto" => 2688 "Ancho" => 2649 "Tamanyo" => 474103 ] ] "descripcion" => array:1 [ "en" => "CONSORT diagram." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Y.-H. Tseng, Y.-C. Tseng, H.-S. Hsu, S.-C. Chang" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Y.-H." "apellidos" => "Tseng" ] 1 => array:2 [ "nombre" => "Y.-C." "apellidos" => "Tseng" ] 2 => array:2 [ "nombre" => "H.-S." "apellidos" => "Hsu" ] 3 => array:2 [ "nombre" => "S.-C." "apellidos" => "Chang" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0873215915364930?idApp=UINPBA00004E" "url" => "/08732159/0000002100000005/v0_201604141143/X0873215915364930/v0_201604141143/en/main.assets" ] "itemAnterior" => array:16 [ "pii" => "X0873215915364914" "issn" => "08732159" "doi" => "10.1016/j.rppnen.2015.04.003" "estado" => "S300" "fechaPublicacion" => "2015-09-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2015;21:233-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5371 "formatos" => array:3 [ "EPUB" => 228 "HTML" => 4030 "PDF" => 1113 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "Exercise capacity impairment in COPD patients with comorbidities" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "233" "paginaFinal" => "238" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G.P.F. Da Silva, M.T.A. Pessoa Morano, A.G. De Matos Cavalcante, N.M. De Andrade, E. De Francesco Daher, E.D.B. Pereira" "autores" => array:6 [ 0 => array:2 [ "nombre" => "G.P.F." "apellidos" => "Da Silva" ] 1 => array:2 [ "nombre" => "M.T.A. Pessoa" "apellidos" => "Morano" ] 2 => array:2 [ "nombre" => "A.G. De Matos" "apellidos" => "Cavalcante" ] 3 => array:2 [ "Iniciales" => "N.M." "apellidos" => "De Andrade" ] 4 => array:2 [ "nombre" => "E. De Francesco" "apellidos" => "Daher" ] 5 => array:2 [ "nombre" => "E.D.B." "apellidos" => "Pereira" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0873215915364914?idApp=UINPBA00004E" "url" => "/08732159/0000002100000005/v0_201604141143/X0873215915364914/v0_201604141143/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "titulo" => "Correlations between osteoprotegerin serum levels and body composition parameters in patients with sleep apnea syndrome and the possible influence on cardiovascular risk" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "239" "paginaFinal" => "244" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Kosacka, P. Piesiak, I. Porebska, R. Jankowska" "autores" => array:4 [ 0 => array:4 [ "Iniciales" => "M." "apellidos" => "Kosacka" "email" => array:1 [ 0 => "mokka113@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 1 => array:3 [ "Iniciales" => "P." "apellidos" => "Piesiak" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "Iniciales" => "I." "apellidos" => "Porebska" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "Iniciales" => "R." "apellidos" => "Jankowska" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Department of Pulmonology and Lung Cancer, Wroclaw Medical University, Wroclaw, Poland" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "<span class="elsevierStyleSup">*</span>" "correspondencia" => "Corresponding author. mokka113@hotmail.com" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v21n05-90436492fig1.jpg" "Alto" => 1243 "Ancho" => 1625 "Tamanyo" => 142941 ] ] "descripcion" => array:1 [ "en" => "Differences in osteoprotegerin serum levels between OSA patients with cardiovascular disease (CVD) and OSA without CVD. Abbreviations: SEM, standard error of the mean; SD, standard deviation." ] ] ] "textoCompleto" => "<a name="sec0005" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStylePara">Osteoprotegerin (OPG) belongs to the TNF (tumor necrosis factor) receptor family. This soluble glycoprotein is a key regulator in bone turnover.<a href="#bib30" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a> OPG inhibits osteoclast differentiation and bone resorption.<a href="#bib31" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib32" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a> However OPG expression has been observed not only in bone but also in many other human tissues, including endothelial and smooth vascular cells.<a href="#bib31" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a> Osteoprotegerin is a decoy receptor for two important ligands: RANKL (receptor activator of nuclear factor kappa B ligand) and TRAIL (TNF-related apoptosis-inducing ligand). OPG prevents TRAIL-induced apoptosis and inhibits nuclear factor kappa B, which plays a role in regulating inflammation, innate immunity and the vascular system.<a href="#bib30" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">, </span><a href="#bib31" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib33" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a> The presence of OPG was reported in atherosclerotic plaque<a href="#bib34" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> and many authors treat OPG as a mediator of vascular calcification, which is a key part of the atherosclerotic process.<a href="#bib30" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">, </span><a href="#bib31" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib33" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a> In addition, studies have shown that OPG is involved in the development of many cardiovascular diseases and their complications.<a href="#bib31" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib35" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">, </span><a href="#bib36" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">Bioelectrical impedance analysis (BIA) is a reliable, non-invasive and effective technique for measuring body composition. The principle of BIA is to determine the electric impedance of an electrical current passing through the body. BIA analysis uses the changes in electric current flow through the body depending on its composition and the electrical resistance of the different tissues.<a href="#bib37" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">, </span><a href="#bib38" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a> This body composition measurement method was evaluated in different groups of patients including healthy subjects, COPD patients and cancer patients.<a href="#bib39" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">, </span><a href="#bib40" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">11</span></a></p><p class="elsevierStylePara">The aim of this study was to evaluate the correlations between osteoprotegerin serum levels and body composition parameters in sleep apnea patients and their influence on cardiovascular risk.</p><a name="sec0010" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Materials and methods</span><a name="sec0015" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Patients</span><p class="elsevierStylePara">A total of 125 patients with newly diagnosed obstructive sleep apnea (OSA) syndrome were enrolled in the study. The group examined comprised 91 males and 34 females with a mean age of 54.48 ± 8.81 years. The majority of patients had severe OSA with mean AHI (apnea hypopnea index) of 33.16 ± 20.44/h. Almost all subjects were overweight or obese with mean BMI (body mass index) 33.76 ± 7.18. Many cardiovascular co-morbidities were observed in the OSA patients: 82 had hypertension, 31 diabetes and 25 ischemic heart disease. We divided the OSA patients into two subgroups: those with cardiovascular diseases and those without. The first group (<span class="elsevierStyleItalic">n</span> = 89) included patients with one or more cardiovascular diseases, only 36 of the patients presented OSA without any other disease.</p><p class="elsevierStylePara">A control group was composed of 59 healthy subjects, including 29 females. The mean age was 51.27 ± 12.97 years and the mean BMI was 29.47 ± 5.42.</p><a name="sec0020" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Polygraphy</span><p class="elsevierStylePara">All subjects underwent a nocturnal respiratory polygraphy using a Grass Aura Lite PSG (Warwick, USA). All examinations were performed in hospital. There following channels were used in our study: nasal pressure airflow signal, pulse, saturation, electrocardiogram (ECG), thorax and abdomen movements, leg movements, snoring and body position. The following parameters were evaluated during 8 h of nocturnal sleep: AHI, desaturation index (DI), mean and minimum SaO<span class="elsevierStyleInf">2</span> at the end of sleep apnea/hypopnea episodes. Apnea was defined as a cessation of airflow for more than 10 s<a href="#bib41" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">12</span></a> and hypopnea as a reduction in airflow by at least 30% of its value during wakefulness for at least 10 s followed by a 4% or greater decrease in oxyhemoglobin saturation.<a href="#bib42" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">13</span></a> An oxygen desaturation event was detected when oxygen saturation fell by at least 4%.</p><a name="sec0025" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Body composition</span><p class="elsevierStylePara">All subjects underwent bioelectrical impedance analysis (BIA) with a single-frequency bioimpedance analyzer (Model BIA 101, AKERN-RJL, Italy). Measurements were taken in the morning, while the patients lay comfortably with their limbs abducted. Current injection electrodes were placed below the phalangeal–metacarpal joint in the middle of the right hand on the dorsal side and below the metatarsal arch on the upper side of the right foot. Detector electrodes were placed on the posterior side of the right wrist and ventrally across the right medial ankle bone. Body composition was determined by injecting 800 μA and 50 kHz of alternating sinusoidal current using standard tetrapolar technique. Body composition parameters were calculated using the BODYGRAM 1.31 software.</p><a name="sec0030" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Osteoprotegerin</span><p class="elsevierStylePara">Blood samples were collected from fasting subjects in the morning. After centrifugation for 10 min at 1467 RCF, the serum was extracted and stored at −80 °C. Osteoprotegerin serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method and the following kit: Human Osteoprotegerin (R&D Systems, Minneapolis, USA). The tests were performed according to the manufacturer's specifications. The ELISA microplate reader from MRXe Dynex Technologies (Chantilly, USA) was used.</p><p class="elsevierStylePara">The following biochemical parameters were also measured in the blood serum sample: CRP, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides.</p><a name="sec0035" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Statistical analysis</span><p class="elsevierStylePara">Statistical analysis was performed using the CSS Statistica software for Windows (version 5.0). Spearman's <span class="elsevierStyleItalic">r</span> correlation coefficient was used to assess the relationship between two variables and the Mann–Whitney <span class="elsevierStyleItalic">U</span> test to compare values between the two groups. Differences between samples were considered significant at <span class="elsevierStyleItalic">p</span> < 0.05.</p><p class="elsevierStylePara">This work has been approved by the institution's relevant ethics committees: the Commission of Bioethics at Wroclaw Medical University. All patients gave their written informed consent to participate in the study.</p><a name="sec0040" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStylePara">Many correlations between osteoprotegerin serum levels and body composition parameters were observed in OSA patients. Osteoprotegerin correlated negatively with muscle mass percentage (MM%), phase angle, fat free mass percentage (FFM%) and body cell mass percentage (BCM%), while higher osteoprotegerin was associated with higher fat mass percentage (FM%). In the control group we were unable to find any correlations between body composition parameters and osteoprotegerin serum levels (<a href="#t0005" class="elsevierStyleCrossRefs">Table 1</a>).</p><p class="elsevierStylePara">Table 1. Correlation coefficients between osteoprotegerin serum levels and selected body composition parameters in OSA patients and control group.</p><a name="t0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Body composition parameters</td><td colspan="4">Osteoprotegerin serum levels</td></tr><tr align="left"><td> </td><td colspan="2">Control group</td><td colspan="2">OSA patients</td></tr><tr align="left"><td> </td><td><span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">s</span></span></td><td><span class="elsevierStyleItalic">p</span></td><td><span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">s</span></span></td><td><span class="elsevierStyleItalic">p</span></td></tr><tr align="left"><td>BMI</td><td>0.075</td><td>NS</td><td>0.112</td><td>NS</td></tr><tr align="left"><td>Phase angle</td><td>−0.018</td><td>NS</td><td>−0.224</td><td><0.05</td></tr><tr align="left"><td>BCM%</td><td>−0.017</td><td>NS</td><td>−0.218</td><td><0.05</td></tr><tr align="left"><td>FM%</td><td>0.108</td><td>NS</td><td>0.216</td><td><0.05</td></tr><tr align="left"><td>FFM%</td><td>−0.108</td><td>NS</td><td>−0.218</td><td><0.05</td></tr><tr align="left"><td>MM%</td><td>−0.091</td><td>NS</td><td>−0.276</td><td><0.05</td></tr><tr align="left"><td>Age</td><td>0.295</td><td><0.05</td><td>0.395</td><td><0.05</td></tr><tr align="left"><td>AHI</td><td>0.107</td><td>NS</td><td>0.144</td><td>NS</td></tr><tr align="left"><td>DI</td><td>0.057</td><td>NS</td><td>0.109</td><td>NS</td></tr><tr align="left"><td>CRP</td><td>0.168</td><td>NS</td><td>0.341</td><td><0.05</td></tr><tr align="left"><td>Total cholesterol</td><td>−0.073</td><td>NS</td><td>0.095</td><td>NS</td></tr><tr align="left"><td>LDL</td><td>−0.063</td><td>NS</td><td>0.019</td><td>NS</td></tr><tr align="left"><td>HDL</td><td>−0.144</td><td>NS</td><td>0.156</td><td>NS</td></tr><tr align="left"><td>Triglycerids</td><td>0.246</td><td>NS</td><td>0.080</td><td>NS</td></tr></table><p class="elsevierStylePara">Higher OPG serum levels were observed in OSA patients with cardiovascular diseases compared with those with OSA without co-morbidities (4.01 vs 3.46 pmol/l, <span class="elsevierStyleItalic">p</span> < 0.05) (<a href="#f0005" class="elsevierStyleCrossRefs">Figure 1</a>). In addition, in the group of OSA patients with cardiovascular diseases, phase angle (5.55 vs 5.98 <span class="elsevierStyleItalic">p</span> < 0.05) and MM% (41.42 vs 45.15 <span class="elsevierStyleItalic">p</span> < 0.05) were lower than in OSA patients without co-morbidities.</p><a name="f0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="320v21n05-90436492fig1.jpg" alt="Differences in osteoprotegerin serum levels between OSA patients with cardiovascular disease (CVD) and OSA without CVD. Abbreviations: SEM, standard error of the mean; SD, standard deviation."></img></p><p class="elsevierStylePara">Figure 1. Differences in osteoprotegerin serum levels between OSA patients with cardiovascular disease (CVD) and OSA without CVD. Abbreviations: SEM, standard error of the mean; SD, standard deviation.</p><p class="elsevierStylePara">There were no statistically significant differences in osteoprotegerin serum levels between OSA patients and those in the control group (3.85 vs 3.93 pmol/l) and we did not observe any correlations between osteoprotegerin and OSA parameters such as AHI, DI or mean saturation.</p><p class="elsevierStylePara">We demonstrated a positive relationship between age and osteoprotegerin in the control group (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">s</span></span> = 0.295; <span class="elsevierStyleItalic">p</span> < 0.05) and in OSA patients (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">s</span></span> = 0.395; <span class="elsevierStyleItalic">p</span> < 0.05). Osteoprotegerin correlated positively with CRP (C-reactive protein) in OSA patients (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">s</span></span> = 0.341; <span class="elsevierStyleItalic">p</span> < 0.05), but not in the control group. No significant correlations were found between OPG and total cholesterol, LDL, HDL or triglycerides in both groups: OSA patients and the control group.</p><a name="sec0045" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Discussion</span><p class="elsevierStylePara">Our study showed many correlations between osteoprotegerin serum levels and body composition parameters in OSA patients. In the literature, we were not able to find any previous studies on osteoprotegerin serum levels in OSA patients and correlations between osteoprotegerin and body composition parameters in this syndrome, so we were only able to use base experimental studies and observations made for other diseases.</p><p class="elsevierStylePara">Einvik et al. examined OPG in patients at high risk of obstructive sleep apnea, however these authors concentrated on associations between depressive syndrome and inflammatory markers. They showed that CRP was associated with depressive symptoms, but did not observe any correlation between depression and OPG or adiponectin.<a href="#bib43" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">14</span></a></p><p class="elsevierStylePara">In our study, in OSA patients the osteoprotegerin correlated negatively with phase angle, FFM%, BCM% and MM% and we also found a positive correlation between osteoprotegerin and FM%. However OPG did not correlate with BMI and the relationship between obesity and OPG is disputable. Gannage-Yared et al. were unable to find any correlation between OPG and BMI, and did not demonstrate differences between OPG levels in obese and non-obese patients.<a href="#bib44" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">15</span></a> In contrast, Ashley et al. observed decreased OPG levels in obese patients and negative correlation with BMI.<a href="#bib45" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">16</span></a></p><p class="elsevierStylePara">Previous findings indicate the relationship between OPG and adipose tissue. After evaluation of OPG expression in the fatty tissue, Pobeha et al. suggested that this expression is related to osteoporosis in COPD patients and OPG acts as mediator between fat mass and bone mineral density.<a href="#bib46" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">17</span></a> In addition, observations made by Frederiksen et al. during testosterone therapy suggested that decreased OPG levels could be associated with changes in fat tissue distribution.<a href="#bib47" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">18</span></a> Our findings that OPG correlated positively with fatty tissue percentage are in contrast to observations made by Eagan et al. In stable COPD patients, these authors showed that a higher FMI (fat mass index) was associated with lower osteoprotegerin plasma levels, whereas FFMI was unrelated to osteoprotegerin.<a href="#bib48" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">19</span></a></p><p class="elsevierStylePara">It is interesting that correlations between osteoprotegerin and body composition parameters were only demonstrated in OSA patients, but not in the control subjects.</p><p class="elsevierStylePara">These findings could be connected with affected bone metabolism in OSA patients and our results may suggest that in OSA patients bone turnover increases with obesity. Unfortunately, we did not take any bone density measurements from the patients examined. The influence of OSA on bone density is disputable. Some studies have suggested an increased risk of osteoporosis in OSA patients connected with increased bone resorption and suppressed bone formation. Uzkeser et al. demonstrated decreased levels of BMD at femoral and lumbar sites in OSA patients<a href="#bib49" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">20</span></a> while other authors showed an increase in the bone resorption marker, reversed by CPAP treatment in about 50% of patients.<a href="#bib50" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">21</span></a> Hypoxia and oxidative stress in particular, which are common in OSA, have a negative effect on bone turnover.<a href="#bib50" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">21</span></a> However other authors present conflicting results. Sforza et al. studied a very large group (833 persons) and found higher femoral and spinal BMD in OSA patients and positive associations between <span class="elsevierStyleItalic">T</span>-scores and AHI and DI.<a href="#bib51" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">22</span></a></p><p class="elsevierStylePara">However OPG could be treated as a marker of vascular damage and correlations between osteoprotegerin and body composition could reflect their influence on cardiovascular risk, especially given that in OSA patients with cardiovascular diseases we demonstrated higher OPG serum levels and lower phase angle and MM%. Our results connecting increased OPG with a higher cardiovascular risk agree with many previous findings.<a href="#bib36" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">, </span><a href="#bib52" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">23</span></a> Blazquez-Medela et al. showed in a large group of patients (<span class="elsevierStyleItalic">n</span> = 191), that OPG could be treated as an indicator of diabetes and hypertension associated vascular pathologies. OPG levels were higher in hypertensive patients with retinopathy, in patients with three or more damaged target organs (heart, vessels, kidney) and in patients with a history of schaemic cardiopathy episodes.<a href="#bib52" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">23</span></a> In addition, it has been demonstrated that, OPG serum levels are higher in patients with carotid plaque than in those without.<a href="#bib53" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">24</span></a></p><p class="elsevierStylePara">A negative correlation with phase angle may also confirm that OPG could indicate an increased risk of cardiovascular diseases in OSA patients. Phase angle provides information about cell membrane function, hydration and body cell mass.<a href="#bib38" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">, </span><a href="#bib54" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">25</span></a> It is a marker of training status and decreased phase angle could indicate impaired nutritional and functional status.<a href="#bib38" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">, </span><a href="#bib54" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">25</span></a> Some studies demonstrated that lower phase angle could be recognized as a new marker of increased cardiovascular risk.<a href="#bib55" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">26</span></a></p><p class="elsevierStylePara">Our observations that OPG correlated positively with age<a href="#bib44" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">, </span><a href="#bib52" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">23</span></a> and CRP<a href="#bib44" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">15</span></a> are in agreement with some previous studies, especially given that OPG is treated as inflammatory marker. We were unable to find any correlations between OPG and cholesterol fractions, as observed by Gannage-Yared et al.<a href="#bib44" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">15</span></a></p><p class="elsevierStylePara">We are aware that our study has several limitations. First of all, the majority of OSA patients examined had cardiovascular diseases (CVD). This proportion was connected with a close association between OSA and cardiovascular morbidity.<a href="#bib56" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">, </span><a href="#bib57" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleSup">, </span><a href="#bib58" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">29</span></a> Some authors have even indicated that OSA should be treated as an independent risk factor for CVD.<a href="#bib56" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">27</span></a> However a bigger group of OSA patients without CVD could be helpful in providing better identification of OSA patients with or without lower cardiovascular risk, which could influence therapeutic approaches in the future. In addition, this group of OSA patients is not well enough described, because the majority of studies concentrate on OSA patients with CVD, as we did. Many mechanisms are connected with higher CVD incidence in OSA, including increased sympathetic activity, oxidative stress, systemic inflammation, abnormal coagulation, endothelial dysfunction and metabolic dysregulation.<a href="#bib56" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">, </span><a href="#bib57" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleSup">, </span><a href="#bib58" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">29</span></a> That is why only one parameter of low OPG serum level is not enough to exclude cardiovascular risk in OSA. Elevated OPG together with some body composition parameters may only suggest increased cardiovascular risk, but more studies are needed to explain these relationships.</p><a name="sec0050" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Conclusion</span><p class="elsevierStylePara">Our findings, combined with previous observations in other diseases, suggest that elevated OPG serum levels together with selected body composition parameters may be helpful in identifying OSA patients with increased cardiovascular risk.</p><a name="sec0055" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Ethical disclosures</span><a name="sec0060" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Protection of human and animal subjects</span><p class="elsevierStylePara">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).</p><a name="sec0065" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p class="elsevierStylePara">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p><a name="sec0070" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p class="elsevierStylePara">The authors declare that no patient data appear in this article.</p><a name="sec0075" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p class="elsevierStylePara">The authors have no conflicts of interest to declare.</p><a name="sec0080" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Authorship</span><p class="elsevierStylePara">MK, PP and IP collected information about patients and performed examinations. MK performed BIA measurements, statistical analysis and drafted manuscript. RJ coordinated the study and made improvements in the manuscript. All authors read and approved the final manuscript.</p><p class="elsevierStylePara">Received 15 October 2014 <br></br>Accepted 24 January 2015 </p><p class="elsevierStylePara">Corresponding author. mokka113@hotmail.com</p>" "pdfFichero" => "320v21n05a90436492pdf001.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec640970" "palabras" => array:3 [ 0 => "Osteoprotegerin" 1 => "OSA" 2 => "Body composition" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><br/><p class="elsevierStylePara">Osteoprotegerin (OPG) is a member of the tumor necrosis factor family and a key regulator in bone turnover; it plays a role in the development of many cardiovascular diseases and may be treated as a marker of vascular damage. Bioelectrical impedance analysis (BIA) is a reliable, non-invasive and effective technique for measuring body composition.</p><p class="elsevierStylePara">The aim of the study was to evaluate correlations between osteoprotegerin serum levels and body composition parameters in sleep apnea patients and their influence on cardiovascular risk.</p><span class="elsevierStyleSectionTitle">Material and methods</span><br/><p class="elsevierStylePara">A total of 125 patients with newly diagnosed OSA were enrolled in the study (including 34 females). The mean age was 54.48 ± 8.81 years, mean AHI 33.16 ± 20.44/h and mean BMI 33.76 ± 7.18. A control group comprised 59 healthy subjects with mean age of 51.27 ± 12.97 years and mean BMI 29.47 ± 5.42.</p><p class="elsevierStylePara">All subjects underwent a nocturnal respiratory polygraphy and body composition measurements were taken with bioelectrical impedance analysis. OPG serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method.</p><span class="elsevierStyleSectionTitle">Results</span><br/><p class="elsevierStylePara">In OSA patients OPG correlated negatively with muscle mass percentage (MM%), phase angle, fat free mass percentage (FFM%) and body cell mass percentage (BCM%), while there was a positive correlation between osteoprotegerin and fat mass percentage (FM%). We demonstrated higher OPG serum levels in OSA patients with cardiovascular diseases than in those without comorbidities (4.01 vs 3.46 pmol/l, <span class="elsevierStyleItalic">p</span> < 0.05).</p><span class="elsevierStyleSectionTitle">Conclusion</span><br/><p class="elsevierStylePara">Our findings, combined with previous observations in other diseases, suggest that elevated OPG serum levels together with selected body composition parameters may be helpful in identifying OSA patients with increased cardiovascular risk.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v21n05-90436492fig1.jpg" "Alto" => 1243 "Ancho" => 1625 "Tamanyo" => 142941 ] ] "descripcion" => array:1 [ "en" => "Differences in osteoprotegerin serum levels between OSA patients with cardiovascular disease (CVD) and OSA without CVD. Abbreviations: SEM, standard error of the mean; SD, standard deviation." ] ] 1 => array:6 [ "identificador" => "fig2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "descripcion" => array:1 [ "en" => "Differences in osteoprotegerin serum levels between OSA patients with cardiovascular disease (CVD) and OSA without CVD. Abbreviations: SEM, standard error of the mean; SD, standard deviation." ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib30" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Osteoprotegerin (OPG) as a biomarker for diabetic cardiovascular complications. Springerplus. 2013; 2:658." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Osteoprotegerin (OPG) as a biomarker for diabetic cardiovascular complications." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Bierre M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/2193-1801-2-658" "Revista" => array:5 [ "tituloSerie" => "Springerplus. " "fecha" => "2013" "volumen" => "2" "paginaInicial" => "658" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24349960" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib31" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Osteoprotegerin: vascular calcification and atherosclerosis. Atherosclerosis. 2009; 204(2):321-9." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Osteoprotegerin: vascular calcification and atherosclerosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Van Campenhout A" 1 => "Golledge J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.atherosclerosis.2008.09.033" "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis. " "fecha" => "2009" "volumen" => "204" "paginaInicial" => "321" "paginaFinal" => "329" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19007931" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib32" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "A new member of tumor necrosis factor ligand family: ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. Biochem Biophys Res Commun. 1999; 256(3):449-55." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "A new member of tumor necrosis factor ligand family: ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Takahashi N" 1 => "Udagawa N" 2 => "Suda T." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/bbrc.1999.0252" "Revista" => array:6 [ "tituloSerie" => "Biochem Biophys Res Commun. " "fecha" => "1999" "volumen" => "256" "paginaInicial" => "449" "paginaFinal" => "455" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10080918" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib33" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappa B ligand in Moenckeberg's sclerosis and atherosclerosis. J Clin Endocrinol Metab. 2004; 89(8):4104-12." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappa B ligand in Moenckeberg's sclerosis and atherosclerosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Schoppet M" 1 => "Al-Fakhri N" 2 => "Franke FE" 3 => "Katz N" 4 => "Barth PJ" 5 => "Maisch B" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2003-031432" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab. " "fecha" => "2004" "volumen" => "89" "paginaInicial" => "4104" "paginaFinal" => "4112" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15292354" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib34" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2001; 21(12):1998-2003." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Dhore CR" 1 => "Cleutjens JP" 2 => "Lutgens E" 3 => "Cleutjens KB" 4 => "Geusens PP" 5 => "Kitslaar PJ" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arterioscler Thromb Vasc Biol. " "fecha" => "2001" "volumen" => "21" "paginaInicial" => "1998" "paginaFinal" => "2003" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11742876" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib35" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "The osteoprotegerin/RANKL/RANKL system: a bone key to vascular disease. Expert Rev Cardiovasc Ther. 2006; 4(6):801-11." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "The osteoprotegerin/RANKL/RANKL system: a bone key to vascular disease." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Kiechl S" 1 => "Werner P" 2 => "Knoflach M" 3 => "Furtner M" 4 => "Willeit J" 5 => "Schett G." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/14779072.4.6.801" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Cardiovasc Ther. " "fecha" => "2006" "volumen" => "4" "paginaInicial" => "801" "paginaFinal" => "811" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17173497" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib36" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease. J Endocrinol Invest. 2009; 32(4):6-9." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D’Amelio P" 1 => "Isaia G" 2 => "Isaia GC." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Endocrinol Invest. " "fecha" => "2009" "volumen" => "32" "paginaInicial" => "6" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19724159" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib37" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Theoretical foundations and practical applications of bioelectrical impedance analysis (BIA). Endokrynologia, Otyłość, Zaburzenia Przemiany Materii. 2007; 3(4):79-84." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Theoretical foundations and practical applications of bioelectrical impedance analysis (BIA)." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Lewitt A" 1 => "Mądro E" 2 => "Krupienicz A." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Endokrynologia, Otyłość, Zaburzenia Przemiany Materii. " "fecha" => "2007" "volumen" => "3" "paginaInicial" => "79" "paginaFinal" => "84" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib38" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "A practical guide to bioelectrical impedance analysis using the example of chronic obstructive pulmonary disease. Nutr J. 2011; 10:35." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "A practical guide to bioelectrical impedance analysis using the example of chronic obstructive pulmonary disease." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Walter-Kroker A" 1 => "Kroker A" 2 => "Mattiucci-Guehlke M" 3 => "Glaab T." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1475-2891-10-35" "Revista" => array:5 [ "tituloSerie" => "Nutr J. " "fecha" => "2011" "volumen" => "10" "paginaInicial" => "35" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21510854" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib39" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Lean body mass estimation by bioelectrical impedance analysis: a four-site cross-validation study. Am J Clin Nutr. 1988; 47(1):7-14." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Lean body mass estimation by bioelectrical impedance analysis: a four-site cross-validation study." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Segal KR" 1 => "Van Loan M" 2 => "Fitzgerald PI" 3 => "Hodgdon JA" 4 => "Van Itallie TB." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Clin Nutr. " "fecha" => "1988" "volumen" => "47" "paginaInicial" => "7" "paginaFinal" => "14" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3337041" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib40" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Bioelectrical impedance phase angle in clinical practice: implications for prognosis in stage IIIB and IV non-small cell lung cancer. BMC Cancer. 2009; 28(9):37." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Bioelectrical impedance phase angle in clinical practice: implications for prognosis in stage IIIB and IV non-small cell lung cancer." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Gupta D" 1 => "Lammersfeld CA" 2 => "Vashi PG" 3 => "King J" 4 => "Dahlk SL" 5 => "Grutsch JF" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "BMC Cancer. " "fecha" => "2009" "volumen" => "28" "paginaInicial" => "37" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib41" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "The Report of an American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep. 1999; 22:667-89." "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Report of an American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research." "idioma" => "en" ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Sleep. " "fecha" => "1999" "volumen" => "22" "paginaInicial" => "667" "paginaFinal" => "689" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10450601" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib42" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Hypopnea in sleep-disordered breathing in adults. Sleep. 2001; 24:469-70." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Hypopnea in sleep-disordered breathing in adults." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Meoli AL" 1 => "Casey KR" 2 => "Clark RW" 3 => "Coleman JA" 4 => "Fayle RW" 5 => "Troell RJ" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Sleep. " "fecha" => "2001" "volumen" => "24" "paginaInicial" => "469" "paginaFinal" => "470" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11403531" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib43" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Novel cardiovascular risk markers in depression: no association between depressive symptoms and osteoprotegerin or adiponectin in persons at high risk for sleep apnea. J Affect Disord. 2013; 145(3):400-4." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Novel cardiovascular risk markers in depression: no association between depressive symptoms and osteoprotegerin or adiponectin in persons at high risk for sleep apnea." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Einvik G" 1 => "Flyybjerg A" 2 => "Hrubos-Strom H" 3 => "Randby A" 4 => "Frystyk J" 5 => "Bierre M" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jad.2012.05.065" "Revista" => array:6 [ "tituloSerie" => "J Affect Disord. " "fecha" => "2013" "volumen" => "145" "paginaInicial" => "400" "paginaFinal" => "404" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22862888" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib44" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study. Eur J Endocrinol. 2008; 158(3):353-9." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Gannage-Yared MH" 1 => "Yaghi C" 2 => "Habre B" 3 => "Khalife S" 4 => "Noun R" 5 => "Germanos-Haddad M" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/EJE-07-0797" "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol. " "fecha" => "2008" "volumen" => "158" "paginaInicial" => "353" "paginaFinal" => "359" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18299469" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib45" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Similar to adiponectin, serum levels of osteoprotegerin are associated with obesity in healthy subjects. Metabolism. 2011; 60(7):994-1000." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Similar to adiponectin, serum levels of osteoprotegerin are associated with obesity in healthy subjects." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Ashley DT" 1 => "O'Sullivan EP" 2 => "Davenport C" 3 => "Devlin N" 4 => "Crowley RK" 5 => "McCaffrey N" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.metabol.2010.10.001" "Revista" => array:6 [ "tituloSerie" => "Metabolism. " "fecha" => "2011" "volumen" => "60" "paginaInicial" => "994" "paginaFinal" => "1000" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21087777" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib46" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease. Bone. 2011; 48(5):1005-14." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Pobeha P" 1 => "Ukropec J" 2 => "Skyba P" 3 => "Ukropcova B" 4 => "Joppa P" 5 => "Kurdiova T" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Bone. " "fecha" => "2011" "volumen" => "48" "paginaInicial" => "1005" "paginaFinal" => "1014" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib47" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat. Horm Metab Res. 2013; 45(4):308-13." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Frederiksen L" 1 => "Glintborg D" 2 => "Hojlund K" 3 => "Hougaard DM" 4 => "Brixen K" 5 => "Rasmussen LM" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-0032-1323647" "Revista" => array:6 [ "tituloSerie" => "Horm Metab Res. " "fecha" => "2013" "volumen" => "45" "paginaInicial" => "308" "paginaFinal" => "313" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22918704" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib48" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Body composition and plasma levels of inflammatory biomarkers in COPD. Eur Respir J. 2010; 36(5):1027-33." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Body composition and plasma levels of inflammatory biomarkers in COPD." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Eagan TM" 1 => "Aukrust P" 2 => "Ueland T" 3 => "Hardie JA" 4 => "Johannessen A" 5 => "Mollnes TE" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00194209" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J. " "fecha" => "2010" "volumen" => "36" "paginaInicial" => "1027" "paginaFinal" => "1033" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20413541" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib49" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Bone mineral density in patients with obstructive sleep apnea syndrome. Sleep Breath. 2013; 17(1):339-42." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Bone mineral density in patients with obstructive sleep apnea syndrome." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Uzkeser H" 1 => "Yildirim K" 2 => "Aktan B" 3 => "Karatay S" 4 => "Kaynar H" 5 => "Araz O" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11325-012-0698-y" "Revista" => array:6 [ "tituloSerie" => "Sleep Breath. " "fecha" => "2013" "volumen" => "17" "paginaInicial" => "339" "paginaFinal" => "342" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22467193" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib50" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Link between obstructive sleep apnea and increased bone resorption in men. Osteoporos Int. 2008; 19(8):1185-92." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Link between obstructive sleep apnea and increased bone resorption in men." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Tomiyama H" 1 => "Okazaki R" 2 => "Inoue D" 3 => "Ochiai H" 4 => "Shijna K" 5 => "Takata Y" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00198-007-0556-0" "Revista" => array:6 [ "tituloSerie" => "Osteoporos Int. " "fecha" => "2008" "volumen" => "19" "paginaInicial" => "1185" "paginaFinal" => "1192" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18224268" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib51" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Obstructive sleep apnea is associated with preserved bone mineral density in healthy elderly subjects. Sleep. 2013; 36(10):1509-15." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Obstructive sleep apnea is associated with preserved bone mineral density in healthy elderly subjects." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Sforza E" 1 => "Thomas T" 2 => "Barthelemy JC" 3 => "Collet P" 4 => "Roche F." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5665/sleep.3046" "Revista" => array:6 [ "tituloSerie" => "Sleep. " "fecha" => "2013" "volumen" => "36" "paginaInicial" => "1509" "paginaFinal" => "1515" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24082310" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib52" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Osteoprotegerin is associated with cardiovascular risk in hypertension and/or diabetes. Eur J Clin Invest. 2012; 42(5):548-56." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Osteoprotegerin is associated with cardiovascular risk in hypertension and/or diabetes." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Blazquez-Medela AM" 1 => "Garcia-Ortiz L" 2 => "Gomez-Marcos MA" 3 => "Recio-Rodriguez JI" 4 => "Sanchez-Rodriguez A" 5 => "Lopez-Novoa JM" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2362.2011.02619.x" "Revista" => array:6 [ "tituloSerie" => "Eur J Clin Invest. " "fecha" => "2012" "volumen" => "42" "paginaInicial" => "548" "paginaFinal" => "556" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22050177" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib53" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Serum osteoprotegerin concentration is associated with carotid atherosclerotic plaque in patients with rheumatoid arthritis. Mod Rheumatol. 2012. [Epub ahead of print]" "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Serum osteoprotegerin concentration is associated with carotid atherosclerotic plaque in patients with rheumatoid arthritis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Asanuma YF" 1 => "Shimada Y" 2 => "Kouzu N" 3 => "Yokota K" 4 => "Nakajima K" 5 => "Sato K" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Mod Rheumatol. " "fecha" => "2012" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib54" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Bioelectrical phase angle and impedance vector analysis—clinical relevance and applicability of impedance parameters. Clin Nutr. 2012; 31(6):854-61." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Bioelectrical phase angle and impedance vector analysis—clinical relevance and applicability of impedance parameters." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Norman K" 1 => "Stobaus N" 2 => "Pirlich M" 3 => "Bosy-Westphal A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clnu.2012.05.008" "Revista" => array:6 [ "tituloSerie" => "Clin Nutr. " "fecha" => "2012" "volumen" => "31" "paginaInicial" => "854" "paginaFinal" => "861" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22698802" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib55" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Relation of phase angle tertiles with blood adipocytokines levels, insulin resistance and cardiovascular risk factors in obese women patients. Eur Rev Med Pharmacol Sci. 2010; 14:521-6." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Relation of phase angle tertiles with blood adipocytokines levels, insulin resistance and cardiovascular risk factors in obese women patients." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "de Luis DA" 1 => "Aller R" 2 => "Romero E" 3 => "Duenas A" 4 => "Perez Castrillon JL." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Rev Med Pharmacol Sci. " "fecha" => "2010" "volumen" => "14" "paginaInicial" => "521" "paginaFinal" => "526" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20712259" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib56" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J. 2007; 29:156-78." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Mc Nicholas WT" 1 => "Bonsigore MR." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00027406" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J. " "fecha" => "2007" "volumen" => "29" "paginaInicial" => "156" "paginaFinal" => "178" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17197482" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib57" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link. Eur Respir J. 2009; 33:1467-84." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Lavie L" 1 => "Lavie P." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00086608" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J. " "fecha" => "2009" "volumen" => "33" "paginaInicial" => "1467" "paginaFinal" => "1484" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19483049" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib58" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome. Thorax. 2009; 64:631-6." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Ryan S" 1 => "Taylor CT" 2 => "Mc Nicholas WT." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2008.105577" "Revista" => array:6 [ "tituloSerie" => "Thorax. " "fecha" => "2009" "volumen" => "64" "paginaInicial" => "631" "paginaFinal" => "636" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19561283" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08732159/0000002100000005/v0_201604141143/X0873215915364922/v0_201604141143/en/main.assets" "Apartado" => array:4 [ "identificador" => "18133" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Artigos originais" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/08732159/0000002100000005/v0_201604141143/X0873215915364922/v0_201604141143/en/320v21n05a90436492pdf001.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0873215915364922?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 4 | 11 |
| 2024 October | 35 | 32 | 67 |
| 2024 September | 45 | 27 | 72 |
| 2024 August | 79 | 39 | 118 |
| 2024 July | 54 | 41 | 95 |
| 2024 June | 49 | 33 | 82 |
| 2024 May | 35 | 30 | 65 |
| 2024 April | 28 | 33 | 61 |
| 2024 March | 35 | 24 | 59 |
| 2024 February | 33 | 28 | 61 |
| 2024 January | 24 | 18 | 42 |
| 2023 December | 22 | 31 | 53 |
| 2023 November | 31 | 33 | 64 |
| 2023 October | 27 | 38 | 65 |
| 2023 September | 22 | 32 | 54 |
| 2023 August | 16 | 19 | 35 |
| 2023 July | 23 | 22 | 45 |
| 2023 June | 18 | 14 | 32 |
| 2023 May | 59 | 26 | 85 |
| 2023 April | 43 | 21 | 64 |
| 2023 March | 92 | 20 | 112 |
| 2023 February | 81 | 27 | 108 |
| 2023 January | 23 | 23 | 46 |
| 2022 December | 56 | 12 | 68 |
| 2022 November | 98 | 51 | 149 |
| 2022 October | 61 | 34 | 95 |
| 2022 September | 56 | 28 | 84 |
| 2022 August | 47 | 41 | 88 |
| 2022 July | 42 | 51 | 93 |
| 2022 June | 24 | 35 | 59 |
| 2022 May | 39 | 38 | 77 |
| 2022 April | 25 | 43 | 68 |
| 2022 March | 36 | 61 | 97 |
| 2022 February | 29 | 36 | 65 |
| 2022 January | 25 | 42 | 67 |
| 2021 December | 25 | 42 | 67 |
| 2021 November | 39 | 33 | 72 |
| 2021 October | 25 | 33 | 58 |
| 2021 September | 16 | 42 | 58 |
| 2021 August | 14 | 27 | 41 |
| 2021 July | 18 | 21 | 39 |
| 2021 June | 19 | 30 | 49 |
| 2021 May | 22 | 32 | 54 |
| 2021 April | 73 | 108 | 181 |
| 2021 March | 80 | 26 | 106 |
| 2021 February | 58 | 30 | 88 |
| 2021 January | 25 | 23 | 48 |
| 2020 December | 22 | 15 | 37 |
| 2020 November | 41 | 26 | 67 |
| 2020 October | 36 | 16 | 52 |
| 2020 September | 40 | 27 | 67 |
| 2020 August | 52 | 23 | 75 |
| 2020 July | 74 | 20 | 94 |
| 2020 June | 51 | 22 | 73 |
| 2020 May | 55 | 16 | 71 |
| 2020 April | 36 | 12 | 48 |
| 2020 March | 44 | 16 | 60 |
| 2020 February | 35 | 17 | 52 |
| 2020 January | 38 | 22 | 60 |
| 2019 December | 58 | 29 | 87 |
| 2019 November | 57 | 24 | 81 |
| 2019 October | 50 | 28 | 78 |
| 2019 September | 62 | 26 | 88 |
| 2019 August | 164 | 15 | 179 |
| 2019 July | 186 | 21 | 207 |
| 2019 June | 196 | 23 | 219 |
| 2019 May | 177 | 16 | 193 |
| 2019 April | 182 | 24 | 206 |
| 2019 March | 206 | 10 | 216 |
| 2019 February | 231 | 9 | 240 |
| 2019 January | 202 | 24 | 226 |
| 2018 December | 124 | 6 | 130 |
| 2018 November | 45 | 3 | 48 |
| 2018 October | 86 | 9 | 95 |
| 2018 September | 18 | 8 | 26 |
| 2018 August | 37 | 25 | 62 |
| 2018 July | 34 | 17 | 51 |
| 2018 June | 53 | 17 | 70 |
| 2018 May | 87 | 11 | 98 |
| 2018 April | 113 | 22 | 135 |
| 2018 March | 40 | 16 | 56 |
| 2018 February | 7 | 7 | 14 |
| 2018 January | 14 | 21 | 35 |
| 2017 December | 24 | 15 | 39 |
| 2017 November | 23 | 26 | 49 |
| 2017 October | 17 | 12 | 29 |
| 2017 September | 17 | 14 | 31 |
| 2017 August | 17 | 10 | 27 |
| 2017 July | 10 | 14 | 24 |
| 2017 June | 15 | 14 | 29 |
| 2017 May | 20 | 19 | 39 |
| 2017 April | 10 | 2 | 12 |
| 2017 March | 12 | 3 | 15 |
| 2017 February | 6 | 4 | 10 |
| 2017 January | 11 | 6 | 17 |
| 2016 December | 6 | 9 | 15 |
| 2016 November | 10 | 6 | 16 |
| 2016 October | 4 | 3 | 7 |
| 2016 September | 6 | 2 | 8 |
| 2016 August | 8 | 7 | 15 |
| 2016 July | 12 | 12 | 24 |
| 2016 April | 20 | 10 | 30 |
| 2016 March | 19 | 19 | 38 |
| 2016 February | 13 | 16 | 29 |
| 2016 January | 35 | 22 | 57 |
| 2015 December | 48 | 47 | 95 |
| 2015 November | 74 | 52 | 126 |
| 2015 October | 105 | 60 | 165 |
| 2015 September | 134 | 113 | 247 |
Show all
