TABLE 1

Overview of main findings from studies investigating effects on cardiovascular outcome of continuous positive airway pressure (CPAP) treatment in obstructive sleep apnoea (OSA) patients

First author [ref.]	Population characteristics	Definition and measurement of OSA	Design/total size for primary analysis	Groups/interventions	(Primary) outcome	Main result
Mil [97]	CAD ≥70% stenosis of a major carotid artery OSA (exclusion of predominant CSA/CSR not reported)	AHI ≥15 events·h⁻¹ In-lab PSG Symptoms consistent with OSA	Prospective, long-term observational cohort study, n=54	Treated OSA, n=25 (nasal CPAP n=21, surgery n=4); median follow-up 86 months Untreated OSA, n=29; median follow-up 90 months	MACCE (cardiovascular mortality, ACS, HF-related hospitalisation, repeat revascularisation)	HR 0.24 (0.09–0.62), treated versus untreated
Stradling [103]	OSA >1 year on CPAP Average compliance >4 h·night⁻¹ AHI <10 events·h⁻¹ on CPAP CSR excluded	ODI >20 events·h⁻¹ (4%) Oximetry during 4 nights off CPAP Previous OSA diagnosis with ODI >20 events·h⁻¹	Prospective, short-term, RCT, n=59	CPAP continuation, n=30 Sham CPAP, n=29 Duration 2 weeks	Blood markers of oxidative stress (MDA, lipid hydroperoxides, total anti-oxidant capacity, superoxide generation from mononuclear cells) Urinary F2-isoprostane Superoxide dismutase as a marker of hypoxic preconditioning	No significant change of blood markers of oxidative stress Urinary F2-isoprostane fell significantly by ∼30% Superoxide dismutase increased similarly
Thunström [102]	CAD OSA Non-sleepy (ESS <10) Predominantly central apnoeas with CSR excluded	AHI >15 events·h⁻¹ Home-based PG	Prospective, long-term RCT RCT arm of RICCADSA trial, n=220	CPAP, n=115 No CPAP, n=105 Follow-up 1 year	Change in circulating levels of inflammatory biomarkers from baseline to 1 year	Inflammatory biomarkers did not change significantly over time, except for IL-6 levels, which reduced to the same extent in the CPAP and no-CPAP groups
Peker [101]	CAD OSA/no OSA Sleepy (ESS ≥10) Predominantly central apnoeas with CSR excluded	AHI >15 events·h⁻¹ (no OSA: AHI <5 events·h⁻¹) In-lab PSG	Prospective, long-term observational cohort study Observational arm of RICCADSA trial, n=267	OSA with CPAP, n=155 No OSA, n=112 Median follow-up 57 months	MACCE (repeat revascularisation, MI, stroke and cardiovascular mortality)	Adjusted HR 0.96 (0.40–2.31), OSA with CPAP versus no OSA
Peker [100]	CAD OSA Non-sleepy (ESS <10) Predominantly central apnoeas with CSR excluded	AHI >15 events·h⁻¹ Home-based PG	Prospective, long-term RCT RCT arm of RICCADSA trial, n=244	CPAP, n=122 No CPAP, n=122 Median follow-up 57 months	MACCE (repeat revascularisation, MI, stroke and cardiovascular mortality)	Adjusted HR 0.62 (0.34–1.13), CPAP versus no CPAP
Lin [99]	MI OSA Including unspecified sleep apnoea	Sleep apnoea as defined by ICD-9-CM 780.51, 780.53, 780.57, 327.23 Partly validated against PSG	Prospective, long-term observational cohort study, n=207	Sleep apnoea diagnosis before MI: with CPAP, n=26; without CPAP, n=74 Sleep apnoea diagnosis after MI: with CPAP, n=33; without CPAP, n=60 Median follow-up 4.2 years	MACCE (repeat MI, repeat revascularisation, hospitalisation for IHD, or stroke)	Sleep apnoea diagnosis before MI: adjusted HR 0.79 (0.55–1.12), no CPAP versus CPAP Sleep apnoea diagnosis after MI: adjusted HR 1.48 (1.01–2.19), no CPAP versus CPAP
Lewis [98]	CAD or ≥3 CAD risk factors OSA ESS ≤15 Predominant CSA excluded HF excluded	AHI ≥15 events·h⁻¹ (max. 50 events·h⁻¹) Home-based sleep study	Prospective, short-term, RCT, n=318	CPAP, n=106 Nocturnal supplemental oxygen, n=106 Healthy lifestyle education, n=106 Duration 12 weeks	HRQoL (SF-36) Depression (PHQ-9)	CPAP improved vitality and mental status (SF-36) with greater improvement with higher levels of sleepiness (ESS ≥12) CPAP gave greater improvement in PHQ-9 scores compared with healthy lifestyle education
McEvoy [92]	CAD (51%) or cerebrovascular disease (49%) OSA ESS ≤15 NYHA III–IV HF excluded CSR excluded	ODI (4%) ≥12 events·h⁻¹ Home-based oximetry and nasal pressure	Prospective, long-term RCT, n=2687	CPAP plus standard of care, n=1346 Standard of care, n=1341 Mean follow-up 3.7 years	MACCE (death from cardiovascular causes, MI, stroke, or hospitalisation for unstable angina, HF, or transient ischaemic attack)	HR 1.10 (0.91–1.32) In CPAP-adherent subgroup, HR 0.80 (0.60–1.07), n=561 CPAP significantly reduced snoring and daytime sleepiness and improved HRQoL and mood
Buchner [93]	OSA 23.6% of patients with CAD Predominant CSA, CSR, hypoventilation syndromes or PLM excluded	AHI ≥5 events·h⁻¹ In-lab PSG	Prospective, long-term observational cohort study, n=449	Treated OSA, n=364 (CPAP n=296, BiPAP n=48, MAD n=20) Untreated OSA, n=85 Median follow-up 72 months	MACCE (death from MI or stroke, MI, stroke, and acute coronary syndrome requiring revascularisation procedures)	Adjusted HR 0.36 (0.21–0.62)
Weaver [95]	OSA Age max. 60 years HF excluded “Other sleep disorders” excluded	AHI ≥15 events·h⁻¹ In-lab PSG	Prospective, short-term, observational, “quasi-experimental” study, n=149	ESS, MSLT, FOSQ normalised on therapy (n=70/106, 30/85, 68/120) ESS, MSLT, FOSQ not normalised on therapy (n=36/106, 55/85, 52/120)	ESS MSLT FOSQ	Those who normalised on therapy used CPAP on average 1.1 (0.2–2.0), 1.1 (0.2–2.1), and 1.0 (0.2–1.8) h·night⁻¹ more than those who did not, for the ESS, MSLT and FOSQ, respectively
Marin [94]	OSA Men only	AHI of different severity levels In-lab PSG	Prospective, long-term, observational cohort study, n=1651	Healthy controls, n=264 Simple snorers, n=377 Untreated mild-to-moderate OSA, n=403 Untreated severe OSA, n=235 OSA plus CPAP, n=372 Mean follow-up 10 years	MACCE, fatal (MI, stroke) MACCE, non-fatal (MI, stroke, CABG, PTCA)	Incidence per 100 person-years of fatal and non-fatal MACCE, respectively: Higher in untreated severe OSA: 1.06 and 2.13 Untreated mild-to-moderate OSA: 0.55, p=0.02, and 0.89, p<0.0001 Simple snorers: 0.34, p=0.0006, and 0.58, p<0.0001 OSA plus CPAP: 0.35, p=0.0008, and 0.64, p<0.0001 Healthy controls: 0.3, p=0.0012, and 0.45, p<0.0001 Adjusted HR for untreated severe OSA: fatal MACCE 2.87 (1.17–7.51) and non-fatal MACCE 3.17 (1.12–7.51) versus healthy controls

CAD: coronary artery disease; CSA: central sleep apnoea; CSR: Cheyne–Stokes respiration; AHI: apnoea–hypopnoea index; PSG: polysomnography; MACCE: major adverse cardiac and cerebrovascular event; ACS: acute coronary syndrome; HF: heart failure; ODI: oxygen desaturation index; RCT: randomised controlled trial; MDA: malondialdehyde; ESS: Epworth Sleepiness Scale; PG: polygraphy; IL: interleukin; MI: myocardial infarction; ICD-9-CM: International Classification of Diseases, 9th Revision, Clinical Modification; IHD: ischaemic heart disease; HRQoL: health-related quality of life; SF-36: 36-item Short-Form Health Survey; PHQ-9: Patient Health Questionnaire-9; NYHA: New York Heart Association; PLM: periodic limb movements; BiPAP: bilevel positive airway pressure; MAD: mandibular advancement device; MSLT: multiple sleep latency test; FOSQ: Functional Outcomes of Sleep Questionnaire; CABG: coronary artery bypass graft surgery; PTCA: percutaneous transluminal coronary angioplasty.