TABLE VII.A.3.

Association between myocardial ischemia, coronary artery disease, and OSA

Study	Year	LOE	Study design	Study groups	Clinical endpoints	Conclusion
Sorajia et al.664	2008	2b	Cross-sectional	202 consecutive patients with no history of coronary disease who underwent electron-beam CT within 3 years of polysomnography between March 1991 and December 2003 were included. OSA was defined by an apnea hypopnea index (AHI)>or =5 events/h, and patients were grouped by quartiles of AHI severity.	Evaluated the association between OSA and the presence of subclinical coronary disease assessed by coronary artery calcification (CAC).	In patients without clinical coronary disease, the presence and severity of OSA is independently associated with the presence and extent of CAC.
Franklin et al.668	1995	2b	Prospective cohort	10 consecutive men with severely disabling angina pectoris and nocturnal angina on at least two nights per week for at least 1 month.	Overnight recordings of nasal and oral airflow, abdominal and chest movements, oxygen saturation, body position, electrocardiogram, electro-oculograms, electroencephalograms, and submental electromyogram were registered.	Results show a relation between nocturnal angina pectoris and sleep apnea.
Mooe et al.669	2000	3b	Observational study	132 men and 94 women	Overnight sleep study and Holter recording to examine disordered breathing (oxyhemoglobin desaturations > or = 4% and apnea-hypopneas), heart rates, and ST-segment depressions (> or = 1 mm, > or = 1 min).	Episodes of nocturnal myocardial ischemia are common in patients with angina pectoris. However, a temporal relationship between sleep-disordered breathing and myocardial ischemia is present only in a minority of the patients, but occurs more frequently in men and in more severely disordered breathing.
Kuniyoshi et al.666	2008	2b	Prospective cohort	92 patients with MI for which the time of onset of chest pain was clearly identified. The presence of OSA was determined by overnight polysomnography.	Evaluate the day-night variation of acute myocardial infarction in patients with obstructive sleep.	The diurnal variation in the onset of MI in OSA patients is strikingly different from the diurnal variation in non-OSA patients. Patients with nocturnal onset of MI have a high likelihood of having OSA. These findings suggest that OSA may be a trigger for MI.
Xie et al.675	2016	2b	Prospective study	112 patients without a prior diagnosis of sleep apnea underwent comprehensive polysomnography within a median of 7 days after MI. Patients were followed up at 6-monthly intervals (±2 weeks) for 48 months.	Investigate the effects of OSA on prognosis after MI, and to determine which specific measures of OSA severity best predicted outcomes.	Nocturnal hypoxemia in OSA is an important predictor of poor prognosis for patients after MI.
Nakashima et al.644	2015	2b	Prospective cohort	Patients with acute MI and followed over time.	The main study outcome measures were cardiac death, recurrence of ACS, and re-admission for heart failure. Major adverse cardiac events (MACEs) were defined as composite end points of individual clinical outcomes.	Moderate-to-severe OSA increased the risk of ACS and the incidence of PCI for progressive lesions. Increased plaque vulnerability might be related to these clinical manifestations.
Shah et al.652	2010	3b	Observational cohort study	1436 enrolled patients, 1024 (71%) had an apnea hypopnea index > or = 5.	Study aimed to determine whether obstructive sleep apnea independently increases the risk of coronary events, including death from cardiovascular causes.	Obstructive sleep apnea increases the risk of coronary events or death from cardiovascular causes.
Lee et al.670	2011	2b	Prospective cohort	120 patients underwent an overnight sleep study during index admission for STEMI.	Determine the effect of severe obstructive sleep apnea (OSA) on long-term outcomes after myocardial infarction.	42% of the patients admitted with STEMI have undiagnosed severe OSA. Severe OSA carries a negative prognostic impact for this group of patients. It is associated with a lower event-free survival rate at 18-month follow-up.
Lee et al.671	2016	2b	Prospective study	Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Median follow-up of 1.9 years.	Hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention.	OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention.
Qu et al.672	2018	1a	Meta-analysis of prospective cohort studies	7 studies including 2465 patients.	Followed up with patients after PCI, and evaluated their overnight sleep patterns within 1 month for major adverse cardiac events (MACEs) as primary outcomes including cardiac death, non-fatal myocardial infarction (MI), and coronary revascularization and secondary outcomes including re-admission for heart failure and stroke.	In patients after PCI, OSA appears to increase the risk of cardiac death, non-fatal MI, and coronary revascularization.
Xie et al.676	2018	2b	Prospective study	112 post-myocardial infarction patients.	Investigate whether excessive daytime sleepiness (EDS) would be an independent prognostic factor after myocardial infarction.	EDS may be an independent prognostic factor of adverse outcome in post-myocardial infarction patients with moderate to severe sleep-disordered breathing.
Gottlieb et al.641	2010	1b	Prospective longitudinal epidemiological study	1927 men and 2495 women > or = 40 years of age and free of coronary heart disease and heart failure at the time of baseline polysomnography were followed up for a median of 8.7 years.	Objective of this study was to assess the relation of obstructive sleep apnea to incident coronary heart disease and heart failure in a general community sample of adult men and women.	Obstructive sleep apnea is associated with an increased risk of incident heart failure in community-dwelling middle-aged and older men; its association with incident coronary heart disease in this sample is equivocal.
Schwarz et al.663	2015	1b	Systematic review and meta-analysis	Systematic review and meta-analysis evaluating RCTs on the effect of CPAP on endothelial function in OSA, assessed by flow-mediated dilatation (FMD) and other validated techniques. Eight RCTs comparing the effects of therapeutic CPAP versus subtherapeutic CPAP (or no intervention) on endothelial function involving 245 OSA patients were included in the systematic review.	Assess the effect CPAP therapy on endothelial function in patients with OSA.	In patients with OSA, CPAP therapy improves endothelial function significantly and to a clinically important extent.
Phillips et al.661	2012	2b	Randomized crossover trial	28 patients received therapeutic or placebo CPAP, each for 2 months with a 1 month washout between treatments. After each treatment period, a 24 h coagulation study was conducted.	Plasminogen activator inhibitor-1 (PAI-1), D-dimer, fibrinogen, von Willebrand Factor (vWF), factor VIII (FVIII), factor VII (FVII), and factor V (FV) were determined at seven time points over the day and night.	CPAP may reduce cardiovascular in OSA, in part through reducing risk of thrombosis.
Milleron et al.658	2004	1a	Long-term prospective study	Studied 54 patients (mean age 57.3 ± 10.1 years) with both CAD (> or = 70% coronary artery stenosis) and OSA (apnea-hypopnoea index > or = 15). In 25 patients, OSA was treated with continuous positive airway pressure (n = 21) or upper airway surgery (n = 4); the remaining 29 patients declined treatment for their OSA.	A composite of cardiovascular death, acute coronary syndrome, hospitalization for heart failure, or need for coronary revascularization.	Treatment of OSA in CAD patients is associated with a decrease in the occurrence of new cardiovascular events, and an increase in the time to such events.
Wu et al.674	2015	2b	Prospective study	390 patients with OSA who had undergone PCI.	Impact of OSA treatment with CPAP on percutaneous coronary intervention (PCI) outcomes.	Untreated moderate–severe OSA was independently associated with a significant increased risk of repeat revascularization after PCI. CPAP treatment reduced this risk.
Peker et al.673	2016	1b	Randomized controlled trial	Consecutive patients with newly revascularized CAD and OSA (apnea hypopnea index ≥15/h) without daytime sleepiness (Epworth Sleepiness Scale score <10) were randomized to auto-titrating CPAP (n = 122) or no positive airway pressure (n = 122).	Determine the effects of CPAP on long-term adverse cardiovascular outcome risk in patients with CAD with nonsleepy OSA.	Routine prescription of CPAP to patients with CAD with nonsleepy OSA did not significantly reduce long-term adverse cardiovascular outcomes in the intention-to-treat population. There was a significant reduction after adjustment for baseline comorbidities and compliance with the treatment.