title: Precision Medicine in Patients With Resistant Hypertension and Obstructive Sleep Apnea: Blood Pressure Response to Continuous Positive Airway Pressure Treatment.
abstract: BACKGROUND
  In patients with resistant hypertension (RH) and obstructive sleep apnea (OSA), the blood pressure response to continuous positive airway pressure (CPAP) treatment is highly variable and could be associated with differential micro-ribonucleic acid (miRNA) profiles. Currently, no available methods exist to identify patients who will respond favorably to CPAP treatment.
  
  
  OBJECTIVE
  The aim of this study was to identify plasma miRNA profiles that predict blood pressure responses to CPAP treatment.
  
  
  METHODS
  Cardiovascular system-focused circulating miRNA expression was evaluated in plasma samples using an 84-miRNA array among patients with RH and OSA at baseline and after 3 months of adherent CPAP use. Pathway analysis and miRNA target gene enrichment were performed in silico. Plasma levels of peptides and hormones related to cardiovascular function were also measured.
  
  
  RESULTS
  The OSA responder group exhibited blood pressure decreases exceeding the observed median (>4.5 mm Hg) after CPAP, which were not present in the nonresponder group (≤4.5 mm Hg) (p < 0.01). Three miRNAs provided a discriminatory predictive model for such a favorable blood pressure response to CPAP (area under the curve: 0.92; p = 0.01). Additionally, CPAP treatment significantly altered a total of 47 plasma miRNAs and decreased aldosterone-to-renin ratios in the responder group (p = 0.016) but not in the nonresponder group.
  
  
  CONCLUSIONS
  A singular pre-CPAP treatment cluster of 3 plasma miRNAs predicts blood pressure responses to CPAP treatment in patients with RH and OSA. CPAP treatment is accompanied by changes in cardiovascular system-related miRNAs that may potentially influence the risk for cardiovascular disease among patients with OSA and RH. (Effect of Continuous Positive Airway Pressure [CPAP] Treatment in the Control of Refractory Hypertension; NCT00616265).
authors: Respiratory Department, Hospital Universitari Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors: Manuel
authors: M
authors: Sánchez-de-la-Torre
authors: Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Pritzker School of Medicine, University of Chicago, Chicago, Illinois; Department of Pediatrics, University of Chicago, Chicago, Illinois.
authors: Abdelnaby
authors: A
authors: Khalyfa
authors: Respiratory Department, Hospital Universitari Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors: Alicia
authors: A
authors: Sánchez-de-la-Torre
authors: Respiratory Department, Hospital Universitari Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors: Montserrat
authors: M
authors: Martinez-Alonso
authors: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Miguel Ángel
authors: MÁ
authors: Martinez-García
authors: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Clinic Analysis and Respiratory Services, Hospital Universitari Son Espases, Institut de Investigacio, Palma de Mallorca, Balears, Spain.
authors: Antonia
authors: A
authors: Barceló
authors: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario Vall Hebrón, Barcelona, Spain.
authors: Patricia
authors: P
authors: Lloberes
authors: Respiratory Department, Hospital Universitario Valme, Sevilla, Spain.
authors: Francisco
authors: F
authors: Campos-Rodriguez
authors: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain.
authors: Francisco
authors: F
authors: Capote
authors: Respiratory Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors: Maria José
authors: MJ
authors: Diaz-de-Atauri
authors: Respiratory Department, Consorcio Sanitario de Terrassa, Barcelona, Spain.
authors: Maria
authors: M
authors: Somoza
authors: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors: Mónica
authors: M
authors: González
authors: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain.
authors: Juan-Fernando
authors: JF
authors: Masa
authors: Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.
authors: David
authors: D
authors: Gozal
authors: Respiratory Department, Hospital Universitari Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain. Electronic address: febarbe.lleida.ics@gencat.cat.
authors: Ferran
authors: F
authors: Barbé
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001795:Blood Pressure Determination; D016000:Cluster Analysis; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010349:Patient Compliance / Q000706:statistics & numerical data; D018570:Risk Assessment; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000150:complications / Q000628:therapy*; D013030:Spain; D017749:Total Quality Management; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D035683:MicroRNAs
keywords: cardiovascular disease; miRNA; personalized medicine; sleep apnea