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array:22 [ "pii" => "S0300289624002837" "issn" => "03002896" "doi" => "10.1016/j.arbres.2024.07.018" "estado" => "S200" "fechaPublicacion" => "2024-09-16" "aid" => "3634" "copyright" => "SEPAR" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:17 [ "pii" => "S0300289624003119" "issn" => "03002896" "doi" => "10.1016/j.arbres.2024.08.002" "estado" => "S200" "fechaPublicacion" => "2024-09-11" "aid" => "3641" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "edi" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">PRO/CON debate</span>" "titulo" => "Etiotypes in COPD: a pro/con debate" "tienePdf" => "en" "tieneTextoCompleto" => "en" "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1739 "Ancho" => 2508 "Tamanyo" => 318154 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Proposed taxonomy (Etiotypes) for COPD.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Reproduced with permission from GOLD. For further explanations, see text.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alvar Agusti, Marc Miravitlles" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Alvar" "apellidos" => "Agusti" ] 1 => array:2 [ "nombre" => "Marc" "apellidos" => "Miravitlles" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289624003119?idApp=UINPBA00003Z" "url" => "/03002896/unassign/S0300289624003119/v2_202409180432/en/main.assets" ] "itemAnterior" => array:16 [ "pii" => "S0300289612000968" "issn" => "03002896" "doi" => "10.1016/j.arbres.2012.02.017" "estado" => "S200" "fechaPublicacion" => "2013-05-08" "aid" => "621" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "ret" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 348 "formatos" => array:2 [ "HTML" => 82 "PDF" => 266 ] ] "en" => array:8 [ "idiomaDefecto" => true "titulo" => "WITHDRAWN: Respiratory Muscle Assessment in Predicting Extubation Outcome in Patients With Stroke" "tienePdf" => "en" "tieneTextoCompleto" => 0 "tieneResumen" => "en" "contieneResumen" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Antonio A.M. Castro, Felipe Cortopassi, Russell Sabbag, Luis Torre-Bouscoulet, Claudia Kümpel, Elias Ferreira Porto" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Antonio A.M." "apellidos" => "Castro" ] 1 => array:2 [ "nombre" => "Felipe" "apellidos" => "Cortopassi" ] 2 => array:2 [ "nombre" => "Russell" "apellidos" => "Sabbag" ] 3 => array:2 [ "nombre" => "Luis" "apellidos" => "Torre-Bouscoulet" ] 4 => array:2 [ "nombre" => "Claudia" "apellidos" => "Kümpel" ] 5 => array:2 [ "nombre" => "Elias Ferreira" "apellidos" => "Porto" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289612000968?idApp=UINPBA00003Z" "url" => "/03002896/unassign/S0300289612000968/v2_201305131254/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "The Effect of Obstructive Sleep Apnea on Subclinical Target Organ Damage in Patients With Resistant Hypertension" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Mireia Dalmases, Manuel Sánchez-de-la-Torre, Dolores Martinez, Olga Minguez, Rafaela Vaca, Lydia Pascual, Maria Aguilá, Esther Gracia-Lavedan, Ivan D. Benitez, Lucía Pinilla, Anunciación Cortijo, Clara Gort-Paniello, Ramon Bascompte Claret, Miguel Ángel Martinez-Garcia, Olga Mediano, Sofía Romero Peralta, Ana Maria Fortuna-Gutierrez, Paola Ponte Marquez, Luciano F. Drager, Mayara Cabrini, Juan Fernando Masa, Jaime Corral Peñafiel, Susana Vázquez, Jorge Abad, Francisco García-Rio, Raquel Casitas, Chi-Hang Lee, Ferran Barbé, Gerard Torres" "autores" => array:29 [ 0 => array:3 [ "nombre" => "Mireia" "apellidos" => "Dalmases" "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" ] ] ] 1 => array:3 [ "nombre" => "Manuel" "apellidos" => "Sánchez-de-la-Torre" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Dolores" "apellidos" => "Martinez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 3 => array:3 [ "nombre" => "Olga" "apellidos" => "Minguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Rafaela" "apellidos" => "Vaca" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "Lydia" "apellidos" => "Pascual" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 6 => array:3 [ "nombre" => "Maria" "apellidos" => "Aguilá" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 7 => array:3 [ "nombre" => "Esther" "apellidos" => "Gracia-Lavedan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 8 => array:3 [ "nombre" => "Ivan D." "apellidos" => "Benitez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 9 => array:3 [ "nombre" => "Lucía" "apellidos" => "Pinilla" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 10 => array:3 [ "nombre" => "Anunciación" "apellidos" => "Cortijo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 11 => array:3 [ "nombre" => "Clara" "apellidos" => "Gort-Paniello" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 12 => array:3 [ "nombre" => "Ramon" "apellidos" => "Bascompte Claret" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 13 => array:3 [ "nombre" => "Miguel Ángel" "apellidos" => "Martinez-Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 14 => array:3 [ "nombre" => "Olga" "apellidos" => "Mediano" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 15 => array:3 [ "nombre" => "Sofía" "apellidos" => "Romero Peralta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 16 => array:3 [ "nombre" => "Ana Maria" "apellidos" => "Fortuna-Gutierrez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 17 => array:3 [ "nombre" => "Paola" "apellidos" => "Ponte Marquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 18 => array:3 [ "nombre" => "Luciano F." "apellidos" => "Drager" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 19 => array:3 [ "nombre" => "Mayara" "apellidos" => "Cabrini" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 20 => array:3 [ "nombre" => "Juan Fernando" "apellidos" => "Masa" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] ] ] 21 => array:3 [ "nombre" => "Jaime" "apellidos" => "Corral Peñafiel" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] ] ] 22 => array:3 [ "nombre" => "Susana" "apellidos" => "Vázquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] ] ] 23 => array:3 [ "nombre" => "Jorge" "apellidos" => "Abad" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">m</span>" "identificador" => "aff0065" ] ] ] 24 => array:3 [ "nombre" => "Francisco" "apellidos" => "García-Rio" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] ] ] 25 => array:3 [ "nombre" => "Raquel" "apellidos" => "Casitas" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] ] ] 26 => array:3 [ "nombre" => "Chi-Hang" "apellidos" => "Lee" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">o</span>" "identificador" => "aff0075" ] ] ] 27 => array:3 [ "nombre" => "Ferran" "apellidos" => "Barbé" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 28 => array:4 [ "nombre" => "Gerard" "apellidos" => "Torres" "email" => array:1 [ 0 => "gtorres@gss.cat" ] "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">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:15 [ 0 => array:3 [ "entidad" => "Sleep Unit, Department of Pulmonary Medicine, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Group of Precision Medicine in Chronic Diseases, Hospital Nacional de Parapléjicos, IDISCAM, Department of Nursing, Physiotherapy and Occupational Therapy, Faculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital Universitari Arnau de Vilanova and Santa Maria, Group of Translational Research in Respiratory Medicine, IRB Lleida, Lleida, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Cardiology Department, Hospital Arnau de Vilanova, Centro de Investigación en Red en Enfermedades Cardiovasculares (CIBERCV), Lleida, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Hospital Universitario y Politécnico La Fe, Respiratory Department, Valencia, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Sleep Unit, Pneumology Department, Hospital Universitario de Guadalajara, Guadalajara, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Sleep Unit, Respiratory Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Internal Medicine, Emergency Department, Hypertension and Cardiovascular Risk Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Bellaterra, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Unidades de Hipertensão, Instituto do Coração (InCor) e Divisão de Nefrologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Hospital San Pedro de Alcantara, Respiratory Dept, Cáceres, Spain" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Hypertension and Vascular Risk Unit, Nephrology Department, Hospital del Mar, Parc de Salut Mar, IMIM, UAB-UPF, Barcelona, Spain" "etiqueta" => "l" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Respiratory Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain" "etiqueta" => "m" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Respiratory Department, Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "n" "identificador" => "aff0070" ] 14 => array:3 [ "entidad" => "Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore" "etiqueta" => "o" "identificador" => "aff0075" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0025" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 250 "Ancho" => 1333 "Tamanyo" => 47074 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Introduction</span><p id="par0020" class="elsevierStylePara elsevierViewall">Resistant hypertension (RH) is defined as blood pressure (BP) that remains above the goal despite the use of three different antihypertensive drugs, including a diuretic, prescribed at the optimal dose or as those that require four or more drugs to achieve BP control.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> Among all hypertensive patients, RH patients have the worst prognosis and have estimated rates of subclinical organ damage (SOD) and cardiovascular events 50% greater than those of patients with controlled hypertension.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">There is a high prevalence of obstructive sleep apnea (OSA) in patients with RH.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">4</span></a> OSA is associated with daytime symptoms, a decrease in quality of life and morbidity and mortality, mainly from cardiovascular alterations.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> It is well known that OSA produces hemodynamic changes, inflammation, oxidative stress, endothelial damage and atherosclerosis<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">5,6</span></a>; therefore, it can potentially produce SOD. Moreover, a dose–response association between OSA severity and BP measurements has been described, especially at night, which could also have an impact on the generation of SOD.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">SOD represents an intermediate stage in the continuum of cardiovascular disease, and it is considered a powerful marker of increased cardiovascular risk that can even predict the recurrence of cardiovascular events.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a> Early detection of SOD in patients with RH who are at high cardiovascular risk is crucial for implementing therapeutic strategies to stop disease progression and possibly favor its regression. Therefore, knowing whether other comorbid conditions frequent in RH patients, such as OSA, could have a synergistic effect on the induction of SOD could be important in the management of these patients, especially when this condition is potentially treatable.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Nevertheless, few studies have evaluated the prevalence of SOD in patients with RH and OSA and they are single-center studies with a cross-sectional design. The aim of this study was to assess the presence of SOD in a large cohort of RH patients with and without OSA, evaluate whether there is a dose–response association with OSA severity, identify the OSA profile associated with the presence of SOD and evaluate the effect of CPAP treatment.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Material and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Study Design and Population</span><p id="par0040" class="elsevierStylePara elsevierViewall">This is an ancillary study to the SARAH study (Long-Term Cardiovascular Outcomes in Patients with RH and OSA with or without Treatment with continuous positive airway pressure (CPAP)), a multicenter, international, prospective, observational cohort study (<a href="ctgov:NCT03002558">NCT03002558</a>) aimed at evaluating the impact of OSA and CPAP treatment on cardiovascular outcomes in patients with RH.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The study included subjects aged 18–75 years diagnosed with RH based on the American Heart Association guidelines<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> and confirmed by 24-h ambulatory blood pressure monitoring (ABPM). The exclusion criteria were RH secondary to other causes (endocrinological, treatment with nonsteroidal anti-inflammatory agents, immunosuppressants or cortisone, renal artery stenosis, intracranial tumors or aortic coarctation), life expectancy<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>1 year and current treatment with CPAP. The methodology of the SARAH trial is published elsewhere.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a> The ethics committee of each participating center approved the study protocol (Ethics Committee number CEIC-1547), and all participants provided informed consent.</p><p id="par0050" class="elsevierStylePara elsevierViewall">For the current study, we selected 503 participants in the SARAH study who had information on at least one of the SOD variables. See the study flow chart in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. Patients were followed once a year for three years.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Procedures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Baseline and Follow-Up Visits</span><p id="par0055" class="elsevierStylePara elsevierViewall">At the initial visit, data regarding sociodemographic characteristics, habits, comorbidities, medication, anthropometric measures and self-reported sleepiness (evaluated with the Epworth Sleepiness Scale (ESS)) were collected. Diabetes and dyslipidemia were determined by self-report, abnormal values in the blood sample analysis or medication use and confirmed by a doctor. Chronic obstructive pulmonary disease, coronary heart disease, heart failure and cerebrovascular diseases were identified by self-reports or medication and confirmed by a doctor or a hospital report. At baseline, we performed a sleep study, 24-h ABPM and an evaluation of SOD. At the follow-up visits, anthropometric measurements, 24-h ABPM and blood samples were collected.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Sleep Evaluation</span><p id="par0060" class="elsevierStylePara elsevierViewall">A sleep test consisting of either respiratory polygraphy or polysomnography was performed on all included subjects. All the studies were performed in accredited sleep units with certified technicians and somnologists. Sleep studies were performed using different types of devices according to their availability at each center. The majority of the studies were performed using Embletta sleep monitor. The rest of the studies were performed using Compumedics E-Profusion 3.4, Sibelmed Exea Serie 5, Philips Respironics Alice 6 LDx, Somnomedics Somnoscreen plus Version 2.7.0 or ApneaLink Resmed. Apnea was defined as an absence or reduction of airflow ≥90% lasting ≥10<span class="elsevierStyleHsp" style=""></span>s. Hypopnea was defined as a reduction in airflow (30–90%) lasting<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>s associated with an oxygen desaturation index (ODI)<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>4% or arousal. The apnea–hypopnea index (AHI) was defined as the number of apnea and hypopnea events per hour of recording or sleep, depending on the study (polygraphy or polysomnography, respectively). CT90 was defined as the percentage of time with an oxygen saturation<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>90%. According to the AHI, participants were classified as non-OSA (AHI<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>15/h) or OSA (AHI<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>15/h). The OSA diagnosis and treatment recommendations were based on guidelines.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> CPAP titration was conducted by means of automated equipment following previously described methods.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> After titration, patients continued treatment with fixed CPAP. Good compliance with CPAP treatment was defined as the use of ≥4<span class="elsevierStyleHsp" style=""></span>h/night.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Blood Pressure Monitoring</span><p id="par0065" class="elsevierStylePara elsevierViewall">Office BP and 24-h ABPM measurements were performed according to the guidelines.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> Based on the 24-h ABPM results, those subjects with a 24-h mean BP that remained above the target (average SBP<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>130<span class="elsevierStyleHsp" style=""></span>mmHg, average DBP<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>80<span class="elsevierStyleHsp" style=""></span>mmHg or both) despite the use of three antihypertensive drugs at full dose (one of which should be a diuretic) or those patients treated with ≥4 antihypertensive medications regardless of the BP values obtained during the 24-h ABPM were included. The devices used to perform the 24-h ABPM were Spacelabs 90207/90217A devices (Spacelabs Inc.), Mortara Ambulo 2400, Microlife WatchBP (Microlife AG), and Dyna-MAPA (Cardios Sistemas Coml. Indl. Ltda.).</p><p id="par0070" class="elsevierStylePara elsevierViewall">All participants maintained their prescribed antihypertensive treatment during the measurements. Compliance with antihypertensive treatment was considered when subjects retrieved from the pharmacy<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>80% of their prescribed medications.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a> In addition, all patients underwent Morisky–Green and Hayness–Sackect test at each follow-up visit.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Subclinical Organ Damage Assessment</span><p id="par0075" class="elsevierStylePara elsevierViewall">The evaluation of SOD at baseline was not compulsory in the SARAH study; therefore, it was performed at the discretion of the physician. During the follow-up, only blood analyses were performed; therefore, only data on the estimated glomerular filtration rate (eGFR) were available. SOD was evaluated as follows:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Cardiac damage:</span> Left ventricular mass (LVM), left atrial diameter (LAD), posterior wall and interventricular septum were evaluated following the American Society of Echocardiography recommendations.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a> Left ventricular hypertrophy (LVH) was defined as an LVM<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>115<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> in men and >95<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> in women. Left atrial enlargement (LAE) was considered when the LAD was >2.3<span class="elsevierStyleHsp" style=""></span>cm/m<span class="elsevierStyleSup">2</span>. Atrial fibrillation (AF) was diagnosed when the patient had a previous history, received antiarrhythmic treatment or was observed via electrocardiography.</p></li><li class="elsevierStyleListItem" id="lsti0025"><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Renal damage</span>: Kidney function was evaluated based on eGFR and/or albuminuria in accordance with the International Kidney Disease guidelines.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a> Microalbuminuria was defined as albuminuria between 30 and 300<span class="elsevierStyleHsp" style=""></span>mg/g creatinine, and proteinuria was defined as albuminuria<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>mg/g in 24<span class="elsevierStyleHsp" style=""></span>h. Alterations should be confirmed in two blood or urine analyses separated by at least 6 months. Kidney damage was defined as an eGFR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and/or an albumin/creatinine ratio<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mg/mmol.</p></li><li class="elsevierStyleListItem" id="lsti0030"><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Vascular disease</span>: The intima-media thickness (IMT) was evaluated by carotid ultrasound following the American Society of Echocardiography recommendations.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a> An increased IMT was defined as an IMT<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.9<span class="elsevierStyleHsp" style=""></span>mm protuberant in the lumen. Peripheral arterial disease was defined by an ankle-brachial index (ABI)<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.9.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a></p></li></ul></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical Analyses</span><p id="par0095" class="elsevierStylePara elsevierViewall">Descriptive statistics were used to determine the characteristics of the study population. The normality of the distributions was assessed by the Shapiro–Wilk test. Normally distributed continuous data were summarized using the mean (standard deviation), and nonnormally distributed continuous data using the median (25th percentile; 75th percentile). Categorical data were summarized using frequencies (percentages). The clinical and sociodemographic characteristics of the patients were compared between the OSA and non-OSA groups using <span class="elsevierStyleItalic">t</span> tests (or equivalent nonparametric tests) or Chi-square tests for quantitative and categorical variables, respectively. SOD parameters were compared among the OSA and non-OSA groups using linear models for continuous variables, tobit regression for truncated variables and logistic regression for dichotomous variables. Unadjusted models and adjusted for confounding factors (age, sex, BMI, alcohol consumption and smoking status) were constructed. The dose–response relationship between the outcomes and the severity of OSA was evaluated using generalized additive models for parameters that showed significant differences between study groups after adjusting for confounding factors. Furthermore, a linear mixed model was fitted to compare the eGFR during follow-up visits (baseline, one year and three years) between OSA patients and non-OSA patients. Patients with OSA who were receiving CPAP treatment were excluded. Patient status was included in the model as a random effect, and study group, visit and their interaction were included as fixed effects. Finally, the eGFR during follow-up visits was assessed according to CPAP adherence (<4 or ≥4<span class="elsevierStyleHsp" style=""></span>h/day) in patients receiving CPAP treatment. Patient status was included in the model as a random effect, and study group, visit and their interaction were included as fixed effects. The level of statistical significance was set at 0.05. All analyses were performed using the statistical software R-project (version 4.1.1).</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Cohort Characteristics</span><p id="par0100" class="elsevierStylePara elsevierViewall">In total, 503 subjects with RH were included. The main sociodemographic and clinical characteristics of the population are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Briefly, the median (IQR) age was 64.0 (57.0–69.0) years, the participants were predominantly male (67.8%), and the median body mass index (BMI) was 31.5<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> (28.4–34.9). The most prevalent comorbidities were hypercholesterolemia (48.4%) and diabetes mellitus (45.9%). A total of 87.6% of the included subjects took ≥4 antihypertensive drugs. Related to the type of antihypertensive drugs, 94.4% take thiazides and loop diuretics, 84.5% calcium channel blockers and 70.6% angiotensin II receptor blockers. No significant differences in antihypertensive treatment were observed between the groups (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Regarding OSA parameters, the median (IQR) AHI was 15.5 (7.90–31.5)<span class="elsevierStyleHsp" style=""></span>events/h, and the median 4%-ODI was 13.0 (6.10–26.8)<span class="elsevierStyleHsp" style=""></span>events/h. The median CT90 was 13.0% (2.20–36.2), and the median ESS was 6 (4–10). The prevalence of OSA (defined as an AHI<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>events/h) was 51.4%. With regard to OSA severity, 24.2% had moderate OSA, and 27.2% had severe OSA. CPAP treatment was indicated in 193 subjects and the mean CPAP compliance at 1-year follow-up was 5.28 (3.95–6.71)<span class="elsevierStyleHsp" style=""></span>h/night, without significant changes during the follow-up period.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Male sex, BMI and ABPM parameters, especially nighttime BP values, were greater in the OSA group than in the non-OSA group. Conversely, there were no differences in the number or type of drugs used between the groups.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Subclinical Organ Damage at Baseline</span><p id="par0115" class="elsevierStylePara elsevierViewall">The SOD parameters were compared between the OSA and non-OSA groups. The evaluation of vascular disease (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>91) revealed that 47.7% of the participants presented increased IMT in the carotid territory, and 15.4% had peripheral arterial disease. There were no statistically significant differences in vascular diseases (neither in carotid nor in peripheral arterial territories) between the groups (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">With regard to cardiac damage (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>191), the mean (SD) of LVM was 119.5 (47.7)<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> in men and 108.4 (30.3)<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> in women, and LVH was observed in 47.2% of men and 65.2% of women. The mean LAD was 2.23 (0.36)<span class="elsevierStyleHsp" style=""></span>cm/m<span class="elsevierStyleSup">2</span>, and 40.4% of patients presented with LAE. Moreover, 10% of the participants had AF. There were no statistically significant differences in cardiac parameters between OSA and non-OSA patients (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><p id="par0125" class="elsevierStylePara elsevierViewall">Regarding kidney parameters (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>452), patients had a mean (SD) eGFR of 73.9 (18.2)<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>. We observed lower values of eGFR in participants with OSA than in those without OSA, with an adjusted effect of −8.42<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> (−13.26, −3.57; <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). The albumin–creatinine ratio was also greater in participants with OSA than in those without OSA, with an adjusted OR (95% CI) of 0.35 (0.00, 0.70; <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.05). The presence of kidney damage was greater in subjects with OSA than in those without OSA, with an adjusted OR (95% CI) of 1.85 (1.13, 3.03; <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). Proteinuria was also slightly greater in the OSA group, although differences did not reach statistical significance after adjusting for confounding factors. For microalbuminuria, no significant differences were detected between the non-OSA and OSA groups after adjusting for confounding factors (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><p id="par0130" class="elsevierStylePara elsevierViewall">The eGFR showed a linear dose–response relationship with OSA severity measured by the AHI (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Specifically, the ODI was the respiratory parameter that was strongly associated with the eGFR (<span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0026) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Evolution of the Glomerular Filtration Rate</span><p id="par0135" class="elsevierStylePara elsevierViewall">The change in eGFR over time according to the presence of OSA was analyzed after excluding patients who underwent CPAP treatment. A longitudinal model showed that the eGFR decreased slightly at the three-year follow-up, with a change (95% CI) from the baseline of −3.12 (−7.58; 1.33)<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>. Compared with the non-OSA group, the OSA group had a mean difference (95% CI) in the eGFR of −7.07<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> (−11.40, −2.79, <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0013) at baseline. These differences were sustained throughout the follow-up, but there were no differences in the evolution trend (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>A). In patients with CPAP, adherence to CPAP treatment was significantly associated with the eGFR at the one-year follow-up, which persisted at three years and was lower in noncompliers (mean differences of −8.21<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> [−13.51, −2.90, <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>B).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">The study showed that patients with RH and OSA do not present differences in vascular or cardiac damage but present worse kidney function than subjects without OSA. Lower eGFR values were observed in OSA patients, with a dose–response relationship with OSA severity. Moreover, the study showed that the ODI is the OSA parameter that has a greater association with the eGFR and indicated that there is an association between adherence to CPAP treatment and kidney function, with lower eGFR in noncompliant subjects.</p><p id="par0145" class="elsevierStylePara elsevierViewall">These results are in line with studies describing a decrease in the eGFR in patients with OSA and an increased risk of kidney disease.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a> OSA is a risk factor for decreased eGFR in patients with hypertension, hypertrophic cardiomyopathy, diabetic kidney disease and in patients without comorbidities,<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">19–21</span></a> with an effect similar to simple hypertension and an additive effect in RH patients.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> We observed a mild reduction in the eGFR, which is consistent with previous studies demonstrating discrete reductions in kidney function.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> The eGFR found in our study, even in the group without OSA, was slightly lower than that described in elderly subjects with OSA from the general population,<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a> suggesting that RH patients may be especially vulnerable to renal damage.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">25</span></a> The relationship between renal damage and OSA could be bidirectional, and we cannot exclude that a decrease in eGFR could produce fluid overload and favor OSA.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> The albumin–creatinine ratio was also greater in subjects with OSA than in those without OSA and proteinuria was slightly greater in the OSA group than in the control group, but these differences did not reach statistical significance after adjusting for confounding factors. Our results are in line with previous studies describing increases in albuminuria in patients with OSA<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> and relating them to OSA severity<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> and as far as we are concerned, these increases have not been previously described in subjects with RH.</p><p id="par0150" class="elsevierStylePara elsevierViewall">The ODI was the sleep parameter that was strongly associated with the eGFR in patients with RH. The kidney medulla is known to be particularly sensitive to hypoxia,<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> and OSA-related hypoxia has been associated with kidney disease<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a> and glomerular filtrate loss.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> Hypertension produces renal damage through glomerular hypertension and hyperfiltration, and hypoxia mainly affects renal damage at the tubulointerstitial level; therefore, both diseases could have an additive effect.</p><p id="par0155" class="elsevierStylePara elsevierViewall">The eGFR at baseline was lower in OSA patients than in non-OSA patients, and if not treated, it decreased slightly throughout the three-year follow-up, but there were no differences in the evolution trend between the groups. The decline in the eGFR found in our study was greater than previously reported in a healthy young cohort,<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a> probably related to the vulnerability of the RH itself to deterioration of renal function. Our results are in agreement with those of Canales et al., who did not observe differences in kidney function trajectory during follow-up but contradict those of other studies.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a> As the follow-up in our study lasted three years, we cannot exclude the possibility that differences could be found over a longer follow-up period because our cohort included a high-risk group (RH patients with an abnormal eGFR at baseline and comorbidities). In subjects receiving CPAP treatment, the results revealed an association between CPAP adherence and the eGFR at the one-year follow-up that persisted at three years, with lower values in noncompliers. Although the effect of OSA treatment on kidney function is not completely clear,<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> our results are in accordance with studies showing that CPAP treatment could improve renal function<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">35,36</span></a> and be related to adherence.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">We did not find differences in cardiac or vascular damage between OSA and non-OSA groups. LVH and carotid atherosclerosis have been previously described, while findings related to LAE and arterial stiffness are less conclusive.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> Previous studies included mainly patients without CV diseases or simple hypertension; therefore, differences in the results could be explained, at least in part, by the heterogeneity in the populations in terms of hypertension phenotype and blood pressure control and also related to differences in OSA severity. There are only two studies in RH subjects that reported a greater incidence of LVH in individuals with moderate/severe OSA than in individuals with no/mild OSA.<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">39,40</span></a> In contrast with our study, the majority of subjects included were women, and the differences could be related to a differential effect depending on sex, as suggested by the greater proportion of LVH observed in women than in men in our study. Moreover, the incidence of LVH in those studies was slightly greater than in our study, even in patients without OSA, probably related to more severe RH and OSA or longer RH than did patients in our cohort.</p><p id="par0165" class="elsevierStylePara elsevierViewall">The main strength of our study is that this is the first multicentric and international study with a longitudinal design evaluating SOD in different territories in a large and well-characterized cohort of patients with RH and OSA. Second, unlike other studies, OSA diagnosis was based on sleep studies instead of questionnaires; therefore, the accuracy of diagnosis and classification is greater. Third, analyses were adjusted for adequate confounding factors.</p><p id="par0170" class="elsevierStylePara elsevierViewall">This study has some limitations. First, the results should not be generalized to subjects with less severe hypertension. Second, the evaluation of SOD was not compulsory, not all patients had all the parameters available at baseline, and only blood analysis data were available at follow-up. Therefore the vascular and cardiac evaluation may have been underpowered to detect differences in SOD. Third, the assessment of the compliance with the antihypertensive treatment was based on the retrieval of the prescribed medication from pharmacy and the Morisky–Green and Hayness–Sackect test, methods that although being widely accepted, are not so accurate than counting the number of doses taken by the patient in each control visit. Forth, we cannot exclude a healthier user bias in patients with good adherence to CPAP treatment. Fifth, for the study design, cause-effect relationship remains unproven. Sixth, we have no data on residual AHI in treated patients.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0175" class="elsevierStylePara elsevierViewall">Our study suggested that OSA may contribute to worsen kidney function in patients with RH, observing a dose–response association with OSA severity. Moreover, greater values of eGFR were detected in those with good CPAP adherence. Therefore, the results highlight the importance of assessing OSA in RH patients with eGFR reduction, even if the reduction is mild, and indicate that in RH patients diagnosed with OSA, stricter control of renal function may be needed. Due to the exploratory nature of the study, future studies are needed to determine the effect of CPAP treatment on the eGFR in RH patients.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding Information</span><p id="par0180" class="elsevierStylePara elsevierViewall">This work was supported by <span class="elsevierStyleGrantSponsor" id="gs1">Instituto de Salud Carlos III</span>, grant <span class="elsevierStyleGrantNumber" refid="gs1">PI16/00489</span>, <span class="elsevierStyleGrantNumber" refid="gs1">PI21/00337</span>, and the <span class="elsevierStyleGrantSponsor" id="gs2">Spanish Respiratory Society</span>. F.B is supported by <span class="elsevierStyleGrantSponsor" id="gs3">ICREA Academia program</span>.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Authors’ Contributions</span><p id="par0185" class="elsevierStylePara elsevierViewall">M.D., F.B., and G.T. had full access to all the data in the study, and G.T. takes responsibility for (is the guarantor) the content of the manuscript, including the data and analysis. M.S., G.T. and F.B. contributed to the study concept and design, data analysis and interpretation, drafting of the manuscript, and critical revision of the manuscript. M.D. contributed to the study concept, coordination of the data acquisition, data analysis, interpretation and writing of the manuscript. E.G.-L. and I.D.B. participated in the study design, performed the statistical analysis and participated in manuscript preparation. All the authors participated in data acquisition, data interpretation, reviewed the article, and approved its submission to Archivos de Bronoconeumología.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Role of Sponsors</span><p id="par0190" class="elsevierStylePara elsevierViewall">The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflicts of Interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare not to have any conflicts of interest that may be considered to influence directly or indirectly the content of the manuscript.</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Artificial Intelligence Involvement</span><p id="par0200" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres2241920" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres2241919" "titulo" => "Highlights" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 2 => array:3 [ "identificador" => "xres2241918" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0025" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusions" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1875680" "titulo" => "Keywords" ] 4 => array:2 [