Tables
- 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.