Rationale: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), many of whom do not report daytime sleepiness. First-line treatment for symptomatic OSA is continuous positive airway pressure (CPAP), but its value in patients without daytime sleepiness is uncertain. Objectives: To determine the effects of CPAP on long-term adverse cardiovascular outcome risk in patients with CAD with nonsleepy OSA. Methods: This single-center, prospective, randomized, controlled, open-label, blinded evaluation trial was conducted between December 2005 and November 2010. 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). Measurements and Main Results: The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Median follow-up was 57 months. The incidence of the primary endpoint did not differ significantly in patients who did versus did not receive CPAP (18.1% vs. 22.1%; hazard ratio, 0.80; 95% confidence interval, 0.46–1.41; P = 0.449). Adjusted on-treatment analysis showed a significant cardiovascular risk reduction in those who used CPAP for ≥4 versus <4 hours per night or did not receive treatment (hazard ratio, 0.29; 95% confidence interval, 0.10–0.86; P = 0.026). Conclusions: 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. Clinical trial registered with www.clinicaltrials.gov (NCT 00519597).

The incidence of a cardiovascular disease (CVD) was explored in a consecutive sleep clinic cohort of 182 middle-aged men (mean age, 46.8 ± 9.3; range, 30–69 years in 1991) with or without obstructive sleep apnea (OSA). All subjects were free of hypertension or other CVD, pulmonary disease, diabetes mellitus, psychiatric disorder, alcohol dependency, as well as malignancy at baseline. Data were collected via the Swedish Hospital Discharge Register covering a 7-year period before December 31, 1998, as well as questionnaires. Effectiveness of OSA treatment initiated during the period as well as age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) at baseline, and smoking habits were controlled. The incidence of at least one CVD was observed in 22 of 60 (36.7%) cases with OSA (overnight oxygen desaturations of 30 or more) compared with in 8 of 122 (6.6%) subjects without OSA (p < 0.001). In a multiple logistic regression model, significant predictors of CVD incidence were OSA at baseline (odds ratio [OR] 4.9; 95% confidence interval [CI], 1.8–13.6) and age (OR 23.4; 95% CI, 2.7–197.5) after adjustment for BMI, SBP, and DBP at baseline. In the OSA group, CVD incidence was observed in 21 of 37 (56.8%) incompletely treated cases compared with in 1 of 15 (6.7%) efficiently treated subjects (p < 0.001). In a multiple regression analysis, efficient treatment was associated with a significant risk reduction for CVD incidence (OR 0.1; 95% CI, 0.0–0.7) after adjustment for age and SBP at baseline in the OSA subjects. We conclude that the risk of developing CVD is increased in middle-aged OSA subjects independently of age, BMI, SBP, DBP, and smoking. Furthermore, efficient treatment of OSA reduces the excess CVD risk and may be considered also in relatively mild OSA without regard to daytime sleepiness.

Previous studies of sleep and breathing suggest an independent association between coronary artery disease (CAD) and obstructive sleep apnoea (OSA) in middle-aged males and females. These studies, however, were criticized because they did not properly adjust for all important confounding factors. In order to better control for the impact of these confounders, a case-control study was performed, matching for age, sex and body mass index (BMI), and additionally adjusting for hypertension, hypercholesterolemia, diabetes mellitus and current smoking. A consecutive selection of 62 patients (44 males and 18 females, mean age 69 yrs, range 44-88 yrs) requiring intensive care for angina pectoris or myocardial infarction at the County Hospital of Skaraborg, Skovde, Sweden, as well as 62 age-, sex- and BMI- matched control subjects without history or signs of heart disease underwent an overnight sleep/ventilatory monitoring study. The time interval between discharge from the intensive care unit and the overnight study ranged between 4 and 21 months. OSA, defined as a Respiratory Disturbance Index (RDI) of > or =10 x h(-1), was present in 19 CAD patients but only in eight control subjects (p=0.017). Using a univariate logistic regression analysis, current smoking (odds ratio (OR) 8.1, 95% confidence interval (CI) 2.2-29.0), diabetes mellitus (OR 4.2, 95% CI 1.1-16.1) and OSA (OR 3.0, 95% CI 1.2-7.5), but not hypertension (OR 1.5, 95% CI 0.7-3.2) and hypercholesterolaemia (OR 1.8, 95% CI 0.7-4.1) were significantly correlated with CAD. In a multiple logistic regression model, current smoking (OR 9.8, 95% CI 2.6-36.5), diabetes mellitus (OR 4.2, 95% CI 1.1-17.1) and OSA (OR 3.1, 95% CI 1.2-8.3) all remained independently associated with CAD. In summary, these data suggest a high occurrence of obstructive sleep apnoea in middle-aged and elderly patients with coronary artery disease requiring intensive care, which should be taken into account when considering risk factors for coronary artery disease.

An increased incidence of cardiovascular disease has previously been reported in middle-aged males during a follow-up period of 7 yrs. The aim of the present study was to address the incidence of coronary artery disease (CAD) in a larger sample without any heart disease at baseline.The population comprised 308 snorers (245 males and 63 females) with a mean±sdage of 49.0±9.9 yrs in 1991. Data were collectedviathe Swedish Hospital Discharge Register, National Cause of Death Registry, clinical charts and questionnaires.Over 7 yrs, CAD was observed in 17 (16.2%) of 105 patients with obstructive sleep apnoea (OSA; overnight (6 h) oxygen desaturations ≥30 events) compared with 11 (5.4%) of 203 snorers without OSA. OSA diagnosis at baseline was associated with an increased risk of development of CAD in a multivariate model. In the OSA group, CAD was confirmed in 16 (24.6%) of 65 incompletely treated patients compared with one (3.9%) of 26 efficiently treated subjects. Efficient treatment of OSA reduced this risk.It is concluded that middle-aged sleep apnoeics are at high risk of developing coronary artery disease if they are not treated efficiently, which should be considered in cardiovascular disease prevention models.

Cardiovascular mortality was prospectively investigated in consecutive coronary artery disease (CAD) patients with versus without obstructive sleep apnea (OSA) during a follow-up period of 5 yr. An overnight sleep/ventilatory study was performed in patients requiring intensive care (n = 62, mean age 67.6 ± 10.4 yr, range 44 to 86) during a stable condition (New York Heart Association [NYHA] functional class I–II) 4 to 21 mo after discharge from the hospital. OSA, defined as a respiratory disturbance index (RDI) of 10/h or more was found in 19 patients (mean RDI 17.5 ± 8.3). Three OSA subjects who were successfully treated with continuous positive airway pressure (CPAP) during the observation period were excluded from the final analysis. There was no statistically significant difference (Fisher two-tailed exact test) between the OSA and non-OSA patient groups in terms of number of elderly subjects (age ⩾ 65 yr), gender, obesity (body mass index [BMI] ⩾ 30 kg/m2), smoking history, presence of hypertension, diabetes mellitus, hypercholesterolemia, or history of myocardial infarction at the study start. During the follow-up period, cardiovascular death occurred in six of 16 OSA patients (37.5%) compared with 4 (9.3%) in the non-OSA group (p = 0.018). The univariate predictors of cardiovascular mortality were RDI (p = 0.007), OSA (p = 0.014), age at baseline (p = 0.028), hypertension at baseline (p = 0.036), history of never-smoking (p = 0.031), and digoxin treatment during the follow-up period (p = 0.013). In a Cox multiple conditional regression model, RDI remained as an independent predictor of cardiovascular mortality (exp β = 1.13, 95% confidence interval [CI] 1.05 to 1.21, two-sided p < 0.001). We conclude that untreated OSA is associated with an increased risk of cardiovascular mortality in patients with CAD. Furthermore, it appears appropriate that RDI is taken into consideration when evaluating secondary prevention models in CAD.