Manuel Sánchez-de-la-Torre1, Abdelnaby Khalyfa2, Alicia Sánchez-de-la-Torre1, Montserrat Martinez-Alonso1, Miguel Ángel Martinez-García3, Antonia Barceló4, Patricia Lloberes5, Francisco Campos-Rodriguez6, Francisco Capote7, Maria José Diaz-de-Atauri8, Maria Somoza9, Mónica González10, Juan-Fernando Masa11, David Gozal12, Ferran Barbé13. 1. 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. 2. 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. 3. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain. 4. 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. 5. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario Vall Hebrón, Barcelona, Spain. 6. Respiratory Department, Hospital Universitario Valme, Sevilla, Spain. 7. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain. 8. Respiratory Department, Hospital Universitario 12 de Octubre, Madrid, Spain. 9. Respiratory Department, Consorcio Sanitario de Terrassa, Barcelona, Spain. 10. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 11. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain. 12. Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Pritzker School of Medicine, University of Chicago, Chicago, Illinois. 13. 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.
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. OBJECTIVES: The aim of this study was to identify plasma miRNA profiles that predict blood pressure responses to CPAP treatment. METHODS:Cardiovascular system-focused circulating miRNAexpression 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).
RCT Entities:
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. OBJECTIVES: 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).