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Rationale: Recent randomized controlled trials did not show cardiovascular benefits of continuous positive airway pressure (CPAP) in adults with coronary artery disease (CAD) and obstructive sleep apnea (OSA) in intention-to-treat analyses. It has been argued that exclusion of patients with OSA with excessive daytime sleepiness (EDS), who may be most likely to benefit from CPAP treatment, may be a reason for the null results. Objectives: We addressed 1 ) the effect of concomitant EDS on adverse outcomes in patients with CAD and OSA; and 2 ) whether the cardiovascular benefit of CPAP adherence differs between individuals with versus without EDS. Methods: This was a secondary analysis of the RICCADSA (Randomized Intervention with CPAP in CAD and Obstructive Sleep Apnea) trial, conducted in Sweden between 2005 and 2013. Data were analyzed from 155 patients with CAD with OSA (apnea-hypopnea index ⩾ 15/h) and EDS (Epworth Sleepiness Scale score ⩾ 10), who were allocated to CPAP and 244 patients without EDS (ESS < 10), who were randomized to CPAP or no CPAP. Patients who were allocated to no CPAP or were nonadherent (CPAP usage < 4 h/night) were compared with adherent patients (CPAP usage ⩾ 4 h/night) at 1-year follow-up. Inverse probability of treatment weighting was applied to mimic randomization of EDS. The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Results: The median follow-up was 52.2 months. The incidence of the primary endpoint did not differ significantly between the EDS versus no-EDS groups in the entire cohort. Within the adherent group, patients without EDS had a significantly decreased risk compared with patients with EDS (adjusted hazard ratio, 0.41; 95% confidence interval, 0.20-0.85; P  = 0.02). Conclusions: Adverse cardiovascular outcomes did not differ by degrees of EDS for patients with CAD with OSA who were untreated or nonadherent to treatment. CPAP use, at least 4 h/night, was associated with reduced adverse outcomes in participants without EDS. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).

Background: Anxiety and obstructive sleep apnea (OSA) coexist among adults with coronary artery disease (CAD) following revascularization. Continuous positive airway pressure (CPAP) is the first line treatment of OSA patients with daytime sleepiness. The current study evaluated the effect of CPAP on anxiety in CAD patients with nonsleepy OSA., Methods: Two hundred forty-four revascularized CAD patients with nonsleepy OSA (apnea-hypopnea index ≥15/h, Epworth Sleepiness Scale score <10) were randomly assigned to CPAP or no-CPAP between 2005 and 2010. Zung Self-rating Anxiety Scale (SAS) was administered at baseline and after 3 and 12 months with higher scores suggesting more anxiety., Results: A total of 208 patients with complete SAS scores at baseline and 12-month follow-up were included (CPAP, n = 103; no-CPAP, n = 105). In the intention-to-treat analysis, CPAP had no significant effect on the SAS scores. On-treatment analysis revealed a significant increase in the median of delta SAS score (+3.75) after three months among the participants using the device 2.8 h/day or more while there was a decline in the median of delta SAS score (-1.25) in the non-adherent or no-CPAP group (p = 0.031). The increase in the SAS score (+1.25) in the adherent group, and the decline (-1.25 points) in the non-adherent/no-CPAP group remained significant after one year (p = 0.011). Baseline SAS score predicted non-adherence [adjusted odds ratio 1.11; 95% confidence interval (CI) 1.04-1.18; p = 0.003], and there was an association between the increase in the SAS scores and accumulated CPAP hours/day [standardized β = 0.144 (95% CI 0.005-0.695), p = 0.047]., Conclusion: Our results suggest that anxiety should be considered in the management of CAD patients with nonsleepy OSA following revascularization., Clinical Trial Registration: NCT00519597., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We explored determinants of depressive mood in adults with coronary artery disease and obstructive sleep apnea and response to positive airway pressure treatment in sleepy and non-sleepy phenotypes. In this secondary analysis of the RICCADSA trial conducted in Sweden, 493 cardiac patients with obstructive sleep apnea (n = 386) or no obstructive sleep apnea (n = 107) with complete Epworth Sleepiness Scale and Zung Self-rating Depression Scale questionnaires were included. Sleepy (Epworth Sleepiness Scale ≥10) versus non-sleepy (Epworth Sleepiness Scale <10) patients with depressive mood (Zung Self-rating Depression Scale score ≥50) were evaluated after 3 and 12 months of positive airway pressure treatment. In all, 133 patients (27.0%) had depressive mood (29.3% of obstructive sleep apnea versus 18.7% of no obstructive sleep apnea; p = 0.029), with a higher percentage among the sleepy phenotype (36.9% versus 24.5%; p = 0.009). In multivariate analysis, depressive mood was significantly associated with female sex, body mass index and Epworth Sleepiness Scale. Among 97 obstructive sleep apnea patients with depressive mood at baseline, there was a significant reduction in the scores at follow-up both in the sleepy and non-sleepy patients allocated to positive airway pressure treatment, whereas no significant changes were observed in the untreated group (p = 0.033). The device use (hr/night) predicted improvement in mood (odds ratio, 1.33; 95% confidence interval, 1.10-1.61; p = 0.003) adjusted for age, female sex, body mass index, left ventricular ejection fraction, apnea-hypopnea index and delta Epworth Sleepiness Scale score. We conclude that obstructive sleep apnea was associated with depressive mood in adults with coronary artery disease. Treatment with positive airway pressure improved mood in both phenotypes, independent of the confounding factors., (© 2019 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Rationale: Obstructive sleep apnea (OSA) and depression are common among adults with coronary artery disease (CAD)., Objectives: To determine the impact of continuous positive airway pressure (CPAP) treatment on depression in adults with CAD and nonsleepy OSA., Methods: This was a secondary analysis of the RICCADSA (Randomized Intervention with CPAP in CAD and Sleep Apnea) trial, conducted in Sweden between 2005 and 2013. Adults with CAD and nonsleepy OSA (apnea-hypopnea index ≥15/h, and Epworth Sleepiness Scale <10 at baseline) and complete Zung Self-Rating Depression Scale (SDS) questionnaires at baseline, after 3 and 12 months, were included. Participants analyzed in their randomized arm were CPAP (n = 99) or no-CPAP (n = 104). Depression was defined as a Zung SDS score of 50 or greater. The primary outcome was the between-group difference in the absolute change in the SDS score from baseline., Results: No significant between-group differences were observed in SDS scores during follow-up in the entire study sample. Among the 56 participants with an SDS of 50 or greater at baseline (27.6%), the mean (±SD) baseline SDS was 55.0 (±5.5) in the CPAP group, and 53.9 (±4.0) in the no-CPAP group. In the CPAP group, SDS scores decreased at 3 months (47.2 ± 8.2) and 12 months (45.8 ± 7.6), but remained stable in the no-CPAP group at 3 months (53.1 ± 8.0) and 12 months (52.6 ± 8.1) (P = 0.01). The proportion with depression decreased from 30.3% at baseline to 16.2% after 3 months, and to 13.1% after 12 months in the CPAP group, from 25.0% at baseline to 23.1% after 3 months, and to 24.0% after 12 months in the no-CPAP group (P = 0.001). Moreover, there was an association between the duration of CPAP usage (h/night) and the longitudinal decline in SDS score (r = 0.46; P < 0.001). CPAP usage categories (3, 4, and 5 h/night) were significantly associated with improvement in SDS (odds ratio = 3.92, 4.45, and 4.89, respectively) in multivariate analyses adjusted for age, sex, body mass index, left ventricular ejection fraction, apnea-hypopnea index, and Epworth Sleepiness Scale at baseline., Conclusions: Among adults with depression, nonsleepy OSA, and CAD, 3 months of CPAP treatment improved depression scores. The improvement in mood persisted up to 12 months. An on-treatment adjusted analysis confirmed these findings. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).

Purpose: Daytime sleepiness, a frequent symptom of obstructive sleep apnea (OSA), can impact functional status. In patients with coronary artery disease (CAD) and concomitant OSA, the distinction between sleep-related functional impairment from underlying CAD versus OSA is unclear. This study evaluated the impact of OSA on sleep-related functional impairment in patients with CAD and compared the effect of 1-year continuous positive airway pressure (CPAP) use on change in impairment between those with and without excessive daytime sleepiness (EDS) and OSA. We hypothesized that sleep-related functional impairment is impacted by EDS independent of OSA in patients with CAD., Methods: One hundred five CAD patients without OSA and 105 with moderate-to-severe OSA from the RICCADSA trial were matched on disease severity and included in the current substudy. Of those with OSA, 80 were allocated to CPAP. Functional Outcomes of Sleep Questionnaire (FOSQ) score < 17.9 corresponded to sleep-related functional impairment., Results: Following revascularization, CAD patients with and without OSA frequently report sleep-related functional impairment (35% and 27.3%, respectively; p = .29). Moderate-to-severe OSA was not related to baseline FOSQ scores < 17.9 in regression analyses; EDS was (OR 4.82, 95% CI 2.12-11.0; p < .001). CPAP use significantly improved FOSQ scores from baseline to 1-year follow-up in OSA patients with EDS (17.2 ± 2.0 to 18.15 ± 1.7, p = .002) despite suboptimal adherence., Conclusions: Sleep-related functional impairment may be reflective of persistent EDS, independent of OSA. Diagnosing OSA and initiating treatment are worthwhile in individuals with CAD and EDS, as both are important to guide appropriate therapy in patients with CAD.

Background: Excessive daytime sleepiness is a frequent symptom of obstructive sleep apnea (OSA) and has been proposed as a motivator for adherence to continuous positive airway pressure (CPAP) therapy. However, excessive daytime sleepiness is absent in many patients with coronary artery disease (CAD) and concomitant OSA. We evaluated long-term use of CPAP and predictors of CPAP use in nonsleepy and sleepy OSA patients from a CAD cohort., Hypothesis: Long-term CPAP use is lower in CAD patients with nonsleepy OSA vs sleepy OSA., Methods: Nonsleepy (Epworth Sleepiness Scale [ESS] score < 10) OSA patients randomized to CPAP (n = 122) and sleepy (ESS ≥10) OSA patients offered CPAP (n = 155) in the RICCADSA trial in Sweden were included in this substudy. The median follow-up was 4.8 years for the main trial, with a predefined minimum follow-up of 2 years., Results: The probability of remaining on CPAP at 2 years was 60% in nonsleepy patients and 77% in sleepy patients. Multivariate analyses indicated that age and hours of CPAP use per night at 1 month were independently associated with long-term CPAP use in nonsleepy patients. In the sleepy phenotype, body mass index, acute myocardial infarction at baseline, and hours of CPAP use per night at 1 month were predictors of long-term CPAP use., Conclusions: Long-term use of CPAP is likely to be challenging for CAD patients with nonsleepy OSA. Early CPAP use is an important predictor of continued long-term use of CPAP, so optimizing patients' initial experience with CPAP could promote adherence., (© 2017 Wiley Periodicals, Inc.)

Sleep apnea and obesity are strongly associated, and both increase the risk for coronary artery disease. Several cross-sectional studies have reported discrepant results regarding the role obesity plays in the relation between sleep apnea and coronary artery calcium (CAC), a marker of subclinical coronary disease. The aim of the present study was to investigate the association between sleep apnea and the presence of CAC in a community cohort of middle-aged men and women without preexisting cardiovascular disease, stratified by body mass index (<30 vs ≥30 kg/m(2)). Participants underwent electron-beam computed tomography to measure CAC and underwent home sleep testing for sleep apnea. The presence of CAC was defined as an Agatston score >0. Sleep apnea was analyzed categorically using the apnea-hypopnea index. The sample was composed of primarily men (61%) and Caucasians (56%), with a mean age of 61 years. The prevalence of CAC was 76%. In participants with body mass indexes <30 kg/m(2) (n = 139), apnea-hypopnea index ≥15 (vs <5) was associated with 2.7-fold odds of having CAC, but the effect only approached significance. Conversely, in participants with body mass indexes ≥30 kg/m(2), sleep apnea was not independently associated with CAC. In conclusion, sleep apnea is independently associated with early atherosclerotic plaque burden in nonobese patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Study Objectives: Sleep apnea has been implicated as an independent risk factor for atherosclerotic coronary artery disease (CAD). An association between the severity of sleep apnea and total cholesterol levels has previously been reported. However, the association with small dense low density lipoprotein (LDL) cholesterol concentration (subclass B), one of the strongest predictors of atherosclerosis, is unknown. We examined the relationship between sleep apnea and LDL subclass B, considering body size., Methods: This is a cross-sectional observational cohort of participants enrolled in a cardiovascular health study. Sleep apnea was assessed with a validated portable monitor. Lipid panels included total cholesterol, triglycerides, high density lipoprotein cholesterol, LDL cholesterol, and LDL subclasses A, B, and A/B. Sleep apnea was analyzed categorically using the apnea hypopnea index (AHI)., Results: A total of 519 participants were evaluated. Mean age was 58.7 ± 7.4 years; BMI was 29.6 ± 5.7; 65% were female; 59% were Caucasian, and 37% were African American. Among participants with abnormal waist circumference by ATP III criteria, moderate to severe sleep apnea (AHI ≥ 25) was not independently associated with LDL subclass B. In contrast, among participants with normal waist circumference, moderate to severe sleep apnea was associated with 4.5-fold odds of having LDL subclass B., Conclusions: Sleep apnea is independently associated with an atherogenic phenotype (LDL subclass B) in non-obese individuals. The association between sleep apnea and LDL subclass B in those with normal waist circumference may account, in part, for the increased risk of atherosclerosis and subsequent vascular events.

Background: Short and less efficient sleep may be risk factors for atherosclerosis. Few studies have investigated the associations between sleep characteristics and early cardiovascular disease (CVD) risk., Objective: Evaluate the associations between coronary artery calcification (CAC) and Framingham risk score profile with sleep characteristics in middle-aged men and women with no history of diagnosed myocardial infarction, interventional cardiology procedures, stroke, diabetes, or sleep disorders., Method: 224 participants enrolled in an epidemiological study of disparities in CVD risk were recruited for a 9-night assessment of sleep, with 2 nights of polysomnography (PSG) and 9 nights of actigraphy and sleep diaries. Of the 224 participants, 110 had high/moderate Framingham risk scores and 114 had low scores; 195 had computed tomography measures of CAC., Results: Individuals who had any CAC or higher Framingham risk scores had elevated apnea/hypopnea index (AHI) values, independent of age, race, and gender. The AHI association with CAC was nonsignificant in analyses adjusting for body mass index (BMI). Those with higher Framingham risk score profiles had shorter PSG sleep duration and less percent stage 3-4 and delta power sleep. High blood pressure and left ventricular hypertrophy were related to AHI and sleep duration, independent of BMI. Neither sleep duration nor efficiency was associated with CAC., Conclusions: CAC was not associated with AHI, independent of BMI in a community-based sample of middle-aged men and women. Framingham risk score profiles were related to poor sleep. Sleep duration may not be related to early plaque burden in relatively healthy individuals.