{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:17:40Z","timestamp":1793726260960,"version":"4.6.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01HL153874"],"award-info":[{"award-number":["R01HL153874"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R01HL153874"],"award-info":[{"award-number":["R01HL153874"]}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (\u0394HR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Here, in this post hoc analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment \u0394HR is associated with greater CPAP-related protection against adverse cardiovascular outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\u0394HR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea\u2013hypopnea index\u2009\u2a7e\u200915 events\/h] with Epworth Sleepiness Scale score\u2009&amp;lt;\u200910; n \u00a0CPAP:n \u00a0control\u2009=\u2009113:113; male, 85%; age, 66\u2009\u00b1\u20098 [mean\u2009\u00b1\u2009SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by \u0394HR (treatment-by-\u0394HR interaction).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The CPAP-related reduction in risk increased progressively with increasing pretreatment \u0394HR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in \u0394HR; P\u2009&amp;lt;\u20090.05). This means that in patients with a \u0394HR of 1 SD above the mean (i.e., 10 beats\/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) (P\u2009&amp;lt;\u20090.05), but no significant risk reduction was estimated in patients with a mean \u0394HR (6 beats\/min; CPAP risk reduction, 16% [\u221253% to 54%]; P\u2009=\u20090.6).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the \u0394HR. Specifically, patients with higher \u0394HR exhibit greater cardiovascular benefit from CPAP therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202111-2608oc","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T10:55:08Z","timestamp":1652784908000},"page":"767-774","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":100,"title":["Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4986-4753","authenticated-orcid":false,"given":"Ali","family":"Azarbarzin","sequence":"first","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0488-9778","authenticated-orcid":false,"given":"Andrey","family":"Zinchuk","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, and Sleep Medicine, Yale Medicine, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wellman","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Labarca","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Vena","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gell","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovico","family":"Messineo","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"},{"name":"Adelaide Institute for Sleep Health, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"White","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8812-8751","authenticated-orcid":false,"given":"Daniel J.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"},{"name":"Medical Service, VA Boston Healthcare System, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Redline","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y\u00fcksel","family":"Peker","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Pulmonary Medicine, Koc University, Istanbul, Turkey"},{"name":"Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Clinical Sciences, Respiratory Medicine, and Allergology, Faculty of Medicine, Lund University, Lund, Sweden; 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