Share
array:23 [ "pii" => "S2254887424000183" "issn" => "22548874" "doi" => "10.1016/j.rceng.2024.01.007" "estado" => "S300" "fechaPublicacion" => "2024-03-01" "aid" => "2167" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Clin Esp. 2024;224:123-32" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0014256524000225" "issn" => "00142565" "doi" => "10.1016/j.rce.2024.01.003" "estado" => "S300" "fechaPublicacion" => "2024-03-01" "aid" => "2167" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Clin Esp. 2024;224:123-32" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Impacto pronóstico de la enfermedad pulmonar obstructiva crónica y el asma bronquial en pacientes con insuficiencia cardiaca" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "123" "paginaFinal" => "132" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3159 "Ancho" => 1675 "Tamanyo" => 369819 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Curvas de Kaplan-Meier para supervivencia global (A), supervivencia libre de ingreso por insuficiencia cardiaca (B) y probabilidad acumulada de muerte cardiovascular o trasplante cardiaco (C) en los tres grupos a estudio.</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">EPOC: enfermedad pulmonar obstructiva crónica.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "E. Barge-Caballero, J. Sieira-Hermida, G. Barge-Caballero, D. Couto-Mallón, M.J. Paniagua-Martín, D. Enríquez-Vázquez, P.J. Marcos-Rodríguez, J. Rodríguez-Capitán, J.M. Vázquez-Rodríguez, M.G. Crespo-Leiro" "autores" => array:10 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Barge-Caballero" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Sieira-Hermida" ] 2 => array:2 [ "nombre" => "G." "apellidos" => "Barge-Caballero" ] 3 => array:2 [ "nombre" => "D." "apellidos" => "Couto-Mallón" ] 4 => array:2 [ "nombre" => "M.J." "apellidos" => "Paniagua-Martín" ] 5 => array:2 [ "nombre" => "D." "apellidos" => "Enríquez-Vázquez" ] 6 => array:2 [ "nombre" => "P.J." "apellidos" => "Marcos-Rodríguez" ] 7 => array:2 [ "nombre" => "J." "apellidos" => "Rodríguez-Capitán" ] 8 => array:2 [ "nombre" => "J.M." "apellidos" => "Vázquez-Rodríguez" ] 9 => array:2 [ "nombre" => "M.G." "apellidos" => "Crespo-Leiro" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2254887424000183" "doi" => "10.1016/j.rceng.2024.01.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887424000183?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256524000225?idApp=WRCEE" "url" => "/00142565/0000022400000003/v1_202403090624/S0014256524000225/v1_202403090624/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2254887424000225" "issn" => "22548874" "doi" => "10.1016/j.rceng.2024.02.004" "estado" => "S300" "fechaPublicacion" => "2024-03-01" "aid" => "2173" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Clin Esp. 2024;224:133-40" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Bibliometric analysis of the official journals of internal medicine societies in Europe" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "133" "paginaFinal" => "140" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis bibliométrico de las revistas oficiales de sociedades de medicina interna en Europa" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2837 "Ancho" => 1675 "Tamanyo" => 373850 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of impact metrics of European internal medicine journals during the 2012–2022 period.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">*Metrics refers to the impact factor (a) and CiteScore (b) in the categories of Internal Medicine (b1) and General Medicine (b2).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Liesa, J.M. Porcel" "autores" => array:2 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Liesa" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Porcel" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256524000377" "doi" => "10.1016/j.rce.2024.01.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256524000377?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887424000225?idApp=WRCEE" "url" => "/22548874/0000022400000003/v1_202403090824/S2254887424000225/v1_202403090824/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "123" "paginaFinal" => "132" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "E. Barge-Caballero, J. Sieira-Hermida, G. Barge-Caballero, D. Couto-Mallón, M.J. Paniagua-Martín, D. Enríquez-Vázquez, P.J. Marcos-Rodríguez, J. Rodríguez-Capitán, J.M. Vázquez-Rodríguez, M.G. Crespo-Leiro" "autores" => array:10 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Barge-Caballero" "email" => array:1 [ 0 => "Eduardo.barge.caballero@sergas.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Sieira-Hermida" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "G." "apellidos" => "Barge-Caballero" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "D." "apellidos" => "Couto-Mallón" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "M.J." "apellidos" => "Paniagua-Martín" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "D." "apellidos" => "Enríquez-Vázquez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 6 => array:3 [ "nombre" => "P.J." "apellidos" => "Marcos-Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 7 => array:3 [ "nombre" => "J." "apellidos" => "Rodríguez-Capitán" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 8 => array:3 [ "nombre" => "J.M." "apellidos" => "Vázquez-Rodríguez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 9 => array:3 [ "nombre" => "M.G." "apellidos" => "Crespo-Leiro" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Servicio de Cardiología, Complejo Hospitalario Universitario de A Coruña (CHUAC), Instituto de Investigación Biomédica de A Coruña (INIBIC), Servicio Galego de Saúde (SERGAS), A Coruña, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Dirección Asistencial y Servicio de Neumología, Complejo Hospitalario Universitario de A Coruña (CHUAC), Instituto de Investigación Biomédica de A Coruña (INIBIC), Servicio Galego de Saúde (SERGAS), A Coruña, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND), Universidad de Málaga, Málaga, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Universidad de A Coruña (UDC), A Coruña, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Impacto pronóstico de la enfermedad pulmonar obstructiva crónica y el asma bronquial en pacientes con insuficiencia cardiaca" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4167 "Ancho" => 2126 "Tamanyo" => 560009 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0100" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curves for overall survival (panel 1A), survival free of admission due to heart failure (panel 1B), and cumulative probability of cardiovascular death or heart transplant (panel 1C) in the three study groups. COPD: chronic obstructive pulmonary disease.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Patients with heart failure (HF) often have a significant number of comorbidities that determine their clinical presentation and prognosis and condition their therapeutic management. Among the associated pathologies, bronchopulmonary diseases such as chronic obstructive pulmonary disease (COPD) and bronchial asthma are particularly relevant.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Around 20% of patients with HF may have COPD,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> the prevalence of which increases with age. The coexistence of COPD and HF is a diagnostic challenge, given that the clinical presentation of both diseases usually overlaps, as well as a therapeutic challenge.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The presence of COPD in patients with HF is associated with more marked symptoms, difficulties in treatment optimization, and a worse prognosis.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In patients with HF, the prevalence of bronchial asthma is lower than that of COPD, but it still may exceed 5%.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> In these individuals, the presence of bronchial asthma has been associated with less use of beta-blockers.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> Its possible prognostic impact is unclear, since there are few published studies and their results are contradictory.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Most of the information in the literature on the clinical and prognostic implications of bronchopulmonary disease in patients with HF comes from population studies in which the clinical follow-up and therapeutic management are heterogeneous. However, it is possible that the unfavorable impact of these associated diseases could be mitigated in a context of specialized care. This study aimed to evaluate the impact of COPD and bronchial asthma on the treatment optimization and prognosis of patients with HF followed-up on and treated in a Cardiology Department HF unit.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study description</span><p id="par0025" class="elsevierStylePara elsevierViewall">A retrospective, observational study was conducted based on a historical cohort of patients with a previous HF diagnosis who were referred to the HF unit of the <span class="elsevierStyleItalic">Complejo Hospitalario Universitario de A Coruña</span> Cardiology Department between January 2010 and June 2022. The care protocol and outcomes of the program have previously been reported.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The information presented in this manuscript was obtained from the SiMon® software tool, a medical record management program developed at this institution. This application includes a registry of data on patients with HF referred to the unit that is prospectively updated by research support staff periodically.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The study protocol was approved by the Clinical Research Ethics Committee of La Coruña-Ferrol. Informed consent for inclusion in the registry was requested from the patient.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables</span><p id="par0040" class="elsevierStylePara elsevierViewall">For this study, data on clinical variables, additional tests, therapeutic management, and adverse clinical outcomes during follow-up were gathered.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Bronchial asthma or COPD were considered to be diagnosed if they were recorded in the patient's medical record. No <span class="elsevierStyleItalic">a posteriori</span> diagnostic reclassification was performed and no further additional tests were requested to actively search for bronchopulmonary disease.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Follow-up and adverse clinical outcomes</span><p id="par0050" class="elsevierStylePara elsevierViewall">Patient follow-up started from the first visit to the HF unit until the date of death or heart transplant or, otherwise, until June 2023.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Adverse clinical outcomes included all-cause mortality and the composite outcome of all-cause death or hospitalization due to HF on the one hand and death due to cardiovascular causes or heart transplant on the other. For the analysis of the composite outcome of all-cause death or hospitalization due to HF, hospitalization in order to perform heart transplant was counted as an episode of hospitalization due to HF.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Categorical variables are shown as percentages and continuous variables as mean and standard deviation. The chi-square test was used to compare categorical variables between groups and Student’s t test, analysis of variance, and the Kruskal-Wallis tests were used, where appropriate, to compare quantitative variables.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The time to the different adverse clinical outcomes evaluated in the study was analyzed using the Kaplan-Meier test while the univariate comparison between groups was performed using the log-rank test.</p><p id="par0070" class="elsevierStylePara elsevierViewall">A multivariate Cox regression was used to control for the effect of potential confounding factors on the statistical association between presence of COPD or bronchial asthma and incidence of the adverse clinical outcomes assessed in the study. Variables with >10% missing values were not taken into consideration in the multivariate analysis.</p><p id="par0075" class="elsevierStylePara elsevierViewall">A multivariate backward stepwise analysis was designed with an elimination criterion of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05. The first stage included covariates that were considered potential confounding factors based on their known association with the prognosis of patients with HF and/or their asymmetrical distribution among the subgroups of patients with COPD, bronchial asthma, or absence of bronchopathy. They included the year of initial consultation, time since HF diagnosis, age, sex, hypertension, diabetes mellitus, tobacco use, alcohol use disorder (>40 g/day), previous admission due to HF, ischemic heart disease, previous neoplasm, peripheral artery disease, implantable defibrillator, NYHA functional class, signs of congestion, hemoglobin, bilirubin, NT-proBNP, heart rate, systolic blood pressure, LVEF, glomerular filtration rate, beta-blocker use, mineralocorticoid receptor antagonist use, renin-angiotensin-aldosterone system inhibitor use, sodium-glucose cotransporter-2 inhibitor use, and loop diuretic use. The final models resulting from this backward stepwise selection process were used to estimate hazard ratios (HR) for each of the adverse clinical outcomes assessed in patients with COPD and patients with bronchial asthma compared to the reference category of patients without bronchopathy.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The statistical analysis was performed with SPSS 25. A significance level of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 was established for all comparisons.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Study population</span><p id="par0085" class="elsevierStylePara elsevierViewall">The sample studied included 2577 patients with a HF diagnosis consecutively referred to the unit between January 2010 and June 2022. Of them, 698 (27.1%) were women. The mean age of the sample was 63.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.1 years. In total, 1935 (75.1%) patients had a left ventricular ejection fraction (LVEF) ≤40%, 295 (11.4%) had a LVEF 41%–49%, and 329 (12.8%) had a LVEF<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>50%. One thousand thirty-nine (40.3%) patients had previously been hospitalized due to HF.</p><p id="par0090" class="elsevierStylePara elsevierViewall">In the first visit, 251 (9.7%, 95% confidence interval (CI)<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8.6%–10.9%) patients with HF also had a previous diagnosis of COPD and 96 (3.7%, 95% CI<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3%–4.5%) had a previous diagnosis of bronchial asthma.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Clinical characteristics</span><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows a comparison of the baseline clinical characteristics of the study patients categorized into three groups according to presence of COPD or bronchial asthma or absence of bronchopulmonary disease. There were significant differences between the study groups in regard to numerous clinical variables of interest.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Patients with COPD had a higher prevalence of tobacco use, alcohol use disorder, previous hospitalization due to HF, and peripheral arterial disease. Furthermore, they had a higher mean age and a longer mean duration of HF. The group of patients with bronchial asthma had a higher prevalence of females and a lower prevalence of ischemic heart disease and myocardial infarction. This group also had the highest proportion of patients referred to the HF unit in the most recent period (2018–2022).</p><p id="par0105" class="elsevierStylePara elsevierViewall">The groups of patients with COPD or bronchial asthma had a higher prevalence of New York Heart Association (NYHA) functional class III or IV and signs of congestion. In addition, the group of patients with COPD had the highest mean basal heart rate, the highest prevalence of atrial fibrillation or flutter and intraventricular conduction disorders, and the longest mean QRS complex duration of the three study groups. They also had the lowest glomerular filtration rate and the highest plasma uric acid levels.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The mean LVEF was similar in patients with COPD or asthma or absence of chronic bronchopulmonary disease. The LVEF was ≤40% in 68 (70.8%) patients with asthma, 194 (77.3%) patients with COPD, and 1678 (75.2%) patients without bronchopathy (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.505).</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Therapeutic management</span><p id="par0115" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the pharmacological treatment as well as treatment with implantable devices in the three study groups at the initial visit and during follow-up in the HF unit.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">In the first visit, the group of patients without bronchopathy had the highest rate of beta-blockers prescribing (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) and previous defibrillator implantation (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.011) of the three study groups, with no significant differences with respect to other treatments.</p><p id="par0125" class="elsevierStylePara elsevierViewall">During follow-up in the HF unit, beta-blockers were prescribed in 2098 (94.1%) patients without bronchopathy, 225 (89.6%) patients with COPD, and 84 (87.5%) patients with bronchial asthma (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002). Sodium-glucose cotransporter-2 inhibitors were prescribed in 854 patients (38.3%) without bronchopathy, 88 (35.1%) patients with COPD, and 48 (50%) patients with asthma (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.036). No significant differences were observed among the groups in regard to other prescriptions.</p><p id="par0130" class="elsevierStylePara elsevierViewall">In total, 647 (29.0%) patients without bronchopathy, 51 (20.3%) patients with COPD, and 20 (20.8%) patients with bronchial asthma had a defibrillator during follow-up (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004) whereas 199 (8.9%) patients without bronchopathy, 15 (6.0%) patients with COPD, and 6 (6.3%) patients with bronchial asthma had a resynchronizer device (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.204).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Follow-up and adverse clinical outcomes</span><p id="par0135" class="elsevierStylePara elsevierViewall">Patients were followed-up on for a median time of 1493 days (interquartile range 752–2585 days). During that period, 777 (30.1%) patients died and 155 (6%) had a heart transplant. In addition, 830 (32.2%) patients required hospitalization due to HF.</p><p id="par0140" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the Kaplan-Meier curves for the cumulative probability of survival (panel 1A), survival free of hospitalization due to HF (panel 1B), and death due to cardiovascular causes or heart transplant (panel 1C) in patients with COPD or bronchial asthma or absence of bronchopathy. For the three outcomes analyzed, the log-rank test showed a significantly worse outcome in the group of patients with COPD compared to the group of patients without bronchopathy (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 for the three outcomes), with no significant differences between the group of patients with bronchial asthma and the group of patients without bronchopathy (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05 for the three outcomes).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Multivariate analysis</span><p id="par0145" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows a summary of the HRs estimated using the Cox multivariate regression method for each of the three adverse clinical outcomes evaluated in the study in patients with COPD or asthma compared to the reference group of patients without bronchopathy.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">The presence of COPD was independently associated with a significantly increased risk of all-cause death (adjusted HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.64, 95% CI 1.33–2.02), all-cause death or hospitalization due to HF (adjusted HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.47, 95% CI 1.22–1.76), and cardiovascular death or heart transplant (adjusted HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.39, 95% CI 1.08–1.79).</p><p id="par0155" class="elsevierStylePara elsevierViewall">The presence of bronchial asthma was not shown to have a significant impact on the risk of any of the three adverse events analyzed (HR for all-cause death<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.98, 95% CI 0.63–1.53; HR for death or hospitalization due to HF<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1, 95% CI 0.72–1.39; HR for cardiovascular death or heart transplant<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.36, 95% CI 0.88–2.11).</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Causes of death</span><p id="par0160" class="elsevierStylePara elsevierViewall">During follow-up, 127 (50.6%) patients with COPD, 22 (22.9%) patients with bronchial asthma, and 628 (28.2%) patients without bronchopathy died. It was possible to identify a cause of death in all cases except 1 (0.8%) death of a patient with COPD and 13 (2.1%) deaths in patients without bronchopathy. The list of the causes of death in each group is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">Cardiovascular causes of death, especially HF and sudden death, were the most common in all three groups, accounting for 75 (59.1%) deaths in patients with COPD, 15 (68.1%) deaths in patients with bronchial asthma, and 394 (62.7%) deaths in patients without bronchopathy.</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0170" class="elsevierStylePara elsevierViewall">This work analyzed the prevalence and prognostic impact of COPD and bronchial asthma in a prospective cohort of patients with HF referred to a specialized Cardiology Department clinical unit between January 2010 and June 2022. The results indicate that both diseases are relatively common in these individuals and their presence is associated with some differences in their clinical profile, therapeutic management, and prognosis. The presence of COPD was independently associated with shorter survival whereas the presence of bronchial asthma was not shown to have a significant prognostic impact.</p><p id="par0175" class="elsevierStylePara elsevierViewall">In unselected populations of patients with HF, the prevalence of COPD is around 20%<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> while the prevalence of bronchial asthma may exceed 5%.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> However, in this study, which was based on a cohort of patients with HF referred to a specialized Cardiology Department unit, a prevalence of COPD of 9.7% and a prevalence of bronchial asthma of 3.7% were observed. Several reasons may explain this apparent discordance in the data on the prevalence of bronchopulmonary disease, which is especially marked in the case of COPD. First, the assignment of a COPD or bronchial asthma diagnosis in this study was made based on presence of the diagnosis in the patient's medical record; there was no active search strategy for these diseases. Therefore, it is possible that some of the milder cases might have gone unnoticed. Second, the study has a selection bias due to the type of patient who is preferentially referred to cardiology department HF programs. These patients are generally younger and have fewer comorbidities than patients with HF attended to in other departments, such as an internal medicine department.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The overrepresentation of the reduced LVEF HF phenotype in this cohort, and also among patients with bronchopulmonary disease, is further evidence of this. Other authors have observed a high prevalence of the preserved LVEF HF phenotype among patients with bronchial asthma<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> or COPD.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">In this cohort, patients with HF and COPD or bronchial asthma had some differential clinical characteristics compared to patients without bronchopathy. As in other series,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> patients with COPD were more frequently male, had an older mean age, and, consequently, a longer duration of HF at the first visit to the specialized clinic. Furthermore, they had a greater prevalence of atrial fibrillation or flutter and a higher prevalence of coronary and peripheral artery disease, which may be related to their age and high prevalence of tobacco use.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Both the presence of COPD and bronchial asthma were associated with more advanced NYHA functional classes and greater prevalence of physical signs of congestion. Patients with COPD had additional signs of severity, such as worse renal function, higher plasma uric acid levels, a higher resting heart rate, a higher prevalence of intraventricular conduction disturbances, and longer QRS complexes. This more severe clinical picture of HF is consistent with previous studies. Indeed, it has been observed that patients with HF and COPD have worse performance parameters on a cardiopulmonary stress test as well as more marked adverse ventricular remodeling than patients with HF without COPD.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The underuse of beta-blockers in patients with HF and COPD or bronchial asthma is a constant in previous studies<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,5,6</span></a> and this work is no exception. In this cohort, the frequency of beta-blocker prescribing in patients with COPD or asthma was higher than what has been reported by other authors.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,5,6</span></a> But even so, it was lower than what has been observed in patients with HF without bronchopulmonary disease. In these patients, caution regarding beta-blocker use is due to the possibility of aggravating the bronchopulmonary disease. However, the available evidence indicates that in patients with bronchopathy and a consolidated cardiovascular indication for beta-blockers, the treatment benefits outweigh the risks, since it is associated with greater survival<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and even with a lower incidence of respiratory decompensation.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> For this reason, the presence of COPD or bronchial asthma is not currently considered a contraindication for starting beta-blockers—preferably cardioselective beta-blockers—with close clinical observation to anticipate the onset of adverse effects.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Another striking result of this study is the relatively higher rate of sodium-glucose cotransporter-2 inhibitors prescribing in patients with bronchial asthma. This may be related to the higher relative proportion of patients with bronchial asthma who were referred to the HF unit in the most recent period and who, therefore, had the opportunity to receive this drug class once its therapeutic indication had become consolidated.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">In this study, a lower frequency of implantable defibrillator implantation was observed in patients with HF and COPD or asthma compared to patients without bronchopulmonary disease. The available evidence supports the efficacy of this therapy in patients with COPD,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> but these individuals have an increased risk of infectious complications<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and pneumothorax <a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>. Moreover, the presence of COPD is independently associated with shorter survival in patients with defibrillators.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The apparent underuse of prophylactic defibrillators in patients with HF and COPD in this study could be related to the different clinical profile of this subgroup: these patients are older, have a greater number of comorbidities, and more advanced HF status. This would result in a less favorable risk-benefit ratio for the therapy.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The reasons that may underlie the relatively low rate of prophylactic defibrillator implantation in patients with HF and bronchial asthma are less clear. This may be the result of the lower relative prevalence of patients with a reduced LVEF HF phenotype in this subgroup, which is the only phenotype for whom this therapy has a clear indication.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In this study, patients with HF and COPD had shorter overall survival, shorter survival free of hospitalization due to HF, and a higher incidence of the composite outcome of cardiovascular death or heart transplant than patients without bronchopulmonary disease. The association between the presence of COPD and an adverse prognosis was maintained in the multivariate models designed to control for possible confounding biases arising from differences in the clinical profile and treatment of these patients. This supports the notion that COPD is a true independent prognostic factor in this population. Other authors have identified similar associations between the presence of COPD and increased risk of all-cause death,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,5,20</span></a> death due to cardiovascular causes,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,20</span></a> and hospitalization due to HF.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> It should be noted that, as in patients without bronchopulmonary disease, cardiovascular causes of death—especially refractory HF and sudden death—were predominant in patients with HF and COPD in this cohort, while noncardiovascular causes such as infections and neoplasms were in the minority. Overall, the results suggest that in patients with HF, the coexistence of COPD not only hinders treatment optimization, but may also contribute to unfavorable progress of HF itself. There is also a pathophysiological basis that supports this hypothesis,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> since it is known that the ventilatory dysfunction, gas exchange abnormalities, and pulmonary hyperinflation characteristic of COPD induce pathological changes in the morphology and size of the heart chambers, hypertrophy, and eccentric ventricular remodeling. This favors the emergence of hemodynamic alterations such as reduced ejection volume and cardiac output; increased systemic and pulmonary artery stiffness; and, in advanced stages, right ventricular failure.</p><p id="par0210" class="elsevierStylePara elsevierViewall">This study did not demonstrate a significant association between the presence of bronchial asthma and prognosis in patients with HF. In both the unadjusted and adjusted analyses, patients with HF and bronchial asthma had an overall survival, HF hospitalization-free survival, and incidence of the composite outcome of cardiovascular death or heart transplant that was comparable to patients without bronchopulmonary disease. In a small Japanese study based on a cohort of 191 patients with HF and without COPD, with a clinical profile different from that of this cohort, with a high prevalence of HF with preserved LVEF and a low rate of beta-blocker prescribing, the presence of bronchial asthma was indeed associated with an increase in all-cause mortality.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> However, in a large cohort of more than 200,000 patients hospitalized due to HF in England and Wales, only the presence of COPD, but not the presence of asthma, was associated with increased in-hospital mortality.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Beyond its potential implications on treatment optimization, it is possible that bronchial asthma’s lack of a clear repercussion on the prognosis of patients with HF is due to its episodic nature and limited impact on cardiovascular function.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Limitations</span><p id="par0215" class="elsevierStylePara elsevierViewall">This study has some limitations arising from its observational nature. The clinical setting in which the study was conducted, namely a HF unit, likely led to selection bias, given the profile of patients referred to these programs. These patients are usually younger, have a higher prevalence of ischemic heart disease and reduced LVEF, and have fewer comorbidities than patients in the general population with HF. For this reason, the external validity of these observations is not guaranteed. In addition, the diagnoses of COPD and bronchial asthma were made exclusively based on their annotation in the patient's medical record. They were not retrospectively reconsidered nor was there an active search for them. The data source used was a routine clinical practice registry; it was not specifically designed for this study. This has resulted in the absence of some information that may be of interest, such as data on the pharmacological treatment of bronchopulmonary disease or respiratory function parameters. Finally, the possibility of confounding biases that could persist despite the multivariate adjustments made, especially in terms of unmeasured clinical characteristics, must be acknowledged.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusions</span><p id="par0220" class="elsevierStylePara elsevierViewall">This study, based on a cohort of 2577 patients with HF attended to in a specialized Cardiology Department clinical unit between January 2010 and June 2022, shows that the coexistence of bronchopulmonary disease (bronchial asthma or COPD) is associated with differences in the clinical profile, treatment, and prognosis of these individuals. In this cohort, patients with HF and bronchial asthma or COPD received beta-blocker therapy and prophylactic defibrillators less frequently than patients without bronchopulmonary disease. The presence of COPD, but not bronchial asthma, was identified as an independent predictor of an adverse prognosis.</p><p id="par0225" class="elsevierStylePara elsevierViewall">Further studies will be necessary in the future to deepen the understanding of the underlying pathophysiological mechanisms in patients with HF and bronchopulmonary disease in order to individualize their clinical management.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of interest</span><p id="par0230" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest related to this publication.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Funding</span><p id="par0235" class="elsevierStylePara elsevierViewall">Some of the authors of the manuscript are members of the CB16/11/00425 group of the <span class="elsevierStyleItalic">Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares</span> (CIBERCV) of the Carlos III Institute of Health.</p><p id="par0240" class="elsevierStylePara elsevierViewall">The study has not received any specific funding other than what the group receives annually for its participation in this thematic network.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres2103835" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Purpose" ] 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" => "xpalclavsec1792943" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1792942" "titulo" => "Abbreviations" ] 3 => array:3 [ "identificador" => "xres2103834" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Propósito" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1792941" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study description" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Variables" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Follow-up and adverse clinical outcomes" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 7 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Clinical characteristics" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Therapeutic management" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Follow-up and adverse clinical outcomes" ] 4 => array:2 [ "identificador" => "sec0060" "titulo" => "Multivariate analysis" ] 5 => array:2 [ "identificador" => "sec0065" "titulo" => "Causes of death" ] ] ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Limitations" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflicts of interest" ] 12 => array:2 [ "identificador" => "sec0090" "titulo" => "Funding" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2024-01-03" "fechaAceptado" => "2024-01-15" "PalabrasClave" => array:2 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1792943" "palabras" => array:5 [ 0 => "Heart failure" 1 => "Prognosis" 2 => "Treatment" 3 => "COPD" 4 => "Bronchial asthma" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1792942" "palabras" => array:6 [ 0 => "COPD" 1 => "LVEF" 2 => "HR" 3 => "HF" 4 => "95% CI" 5 => "NYHA" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1792941" "palabras" => array:5 [ 0 => "Insuficiencia cardiaca" 1 => "Pronóstico" 2 => "Tratamiento" 3 => "EPOC" 4 => "Asma" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox’s methods. Median follow-up was 1493 days.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>89.6%; asthma<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>87.5%; no bronchopathy<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>94.1%; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002) and SGLT2 inhibitors (COPD<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>35.1%; asthma<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>50%; no bronchopathy<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>38.3%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20.3%; asthma<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20.8%; no broncopathy<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>29%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004).</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">COPD was independently associated with increased risk of all-cause mortality (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.64; 95% CI 1.33–2.02), all-cause death or HF admission (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.47; 95% CI 1.22–1.76) and cardiovascular death or heart transplantation (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.39; 95% CI 1.08–1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">COPD, but not asthma, is an adverse independent prognostic factor in patients with HF.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Propósito</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Analizar el impacto de la enfermedad pulmonar obstructiva crónica (EPOC) y el asma bronquial sobre el manejo terapéutico y el pronóstico de los pacientes con insuficiencia cardiaca (IC).</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Análisis de la información contenida en un registro clínico de pacientes remitidos a una unidad especializada de IC entre enero de 2010 y junio de 2022. Se comparó su perfil clínico, tratamiento y pronóstico en base a la presencia de EPOC o asma bronquial. El análisis de supervivencia se realizó mediante los métodos de Kaplan-Meier y Cox. La mediana de seguimiento fue de 1493 días.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 2577 pacientes, de los cuales 251 (9,7%) presentaban EPOC y 96 (3,7%) asma bronquial. Observamos diferencias significativas entre los tres grupos con respecto a la prescripción de betabloqueantes (EPOC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>89,6%; asma<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>87,5%; no broncopatía<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>94,1%; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,002) e inhibidores del cotransportador de sodio-glucosa tipo 2 (EPOC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>35,1%; asma<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>50%; no broncopatía<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>38,3%; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,036). Además, los pacientes con patología bronquial recibieron con menor frecuencia un desfibrilador (EPOC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20,3%; asma<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20,8%; no broncopatía<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>29%; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,004).</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La presencia de EPOC se asoció de forma independiente con mayor riesgo de muerte por cualquier causa (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1,64; IC 95% 1,33–2,02), muerte u hospitalización por IC (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1,47; IC 95% 1,22–1,76) y muerte cardiovascular o trasplante cardiaco (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1,39; IC 95% 1,08–1,79) en comparación con la ausencia de broncopatía. La presencia de asma bronquial no se asoció a un impacto significativo sobre los desenlaces analizados.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">La EPOC, pero no el asma bronquial, es un factor pronóstico adverso e independiente en pacientes con IC.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Propósito" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4167 "Ancho" => 2126 "Tamanyo" => 560009 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0100" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curves for overall survival (panel 1A), survival free of admission due to heart failure (panel 1B), and cumulative probability of cardiovascular death or heart transplant (panel 1C) in the three study groups. COPD: chronic obstructive pulmonary disease.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1009 "Ancho" => 1675 "Tamanyo" => 92910 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0105" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Distribution of causes of death during long-term follow-up in the three study groups. COPD: chronic obstructive pulmonary disease.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0110" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">LVDD: left ventricular diastolic diameter. LVSD: left ventricular systolic diameter. COPD: chronic obstructive pulmonary disease. LVEF: left ventricular ejection fraction. GGT: gamma-glutamyl transferase. AST: aspartate aminotransferase. ALT: alanine aminotransferase. HF: heart failure. NT-proBNP: N-terminal fraction of brain natriuretic propeptide. NYHA: New York Heart Association. PASP: pulmonary artery systolic pressure. TAPSE: tricuspid annular plane systolic excursion. IU: international units.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No bronchopathy(<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2230) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">COPD(<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>251) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bronchial asthma(<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>96) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Year of initial consultation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.013 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2010–2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">530 (23.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 (22.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (10.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2014–2017 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">689 (30.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 (35.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (32.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2018–2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1011 (45.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">104 (41.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55 (57.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous medical history \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" tit