Occurrence and Predictors of Obstructive Sleep Apnea ... - ATS Journals

ORIGINAL RESEARCH Occurrence and Predictors of Obstructive Sleep Apnea in a Revascularized Coronary Artery Disease Cohort Helena Glantz1,2, Erik Thunstrom ¨ 2, Johan Herlitz3, Bjorn ¨ Cederin4, Salmir Nasic5, Jan Ejdeback ¨ 6, and Yuksel ¨ Peker2,5,7 1 Department of Internal Medicine, Skaraborg Hospital, Lidkoping, ¨ Sweden; 2Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Center of Prehospital Care in Western Sweden, University College of Boras ˚ and Sahlgrenska University Hospital, Gothenburg, Sweden; and 4Department of Internal Medicine, 5Center for Research, Development, and Education, 6Department of Cardiology, and 7Sleep Medicine Unit, Skaraborg Hospital, Skovde, ¨ Sweden

Abstract Background: Knowledge about the prevalence of obstructive sleep apnea (OSA) in coronary artery disease (CAD) is insufficient. The aim of the current report was to evaluate the occurrence and predictors of OSA among revascularized patients with CAD within the framework of a randomized controlled trial (Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea [RICCADSA]), evaluating the impact of continuous positive airway pressure on cardiovascular outcomes in CAD patients with OSA. Material and Methods: All patients undergoing percutaneous coronary intervention or coronary artery bypass grafting between September 2005 and November 2010 (n = 1,291) were invited to participate. Anthropometrics and medical history were obtained, ambulatory sleep recording was performed, and all subjects completed the Epworth Sleepiness Scale (ESS) questionnaire. Results: In total, 662 patients participated in the sleep study. OSA, defined as an apnea–hypopnea index equal to or greater than

15/hour, was found among 422 (63.7%). The prevalence of hypertension was 55.9%; obesity (body mass index > 30 kg/m2), 25.2%; diabetes mellitus, 22.1%; and current smoking, 18.9%. The patients with CAD who did not participate in the study demonstrated an almost similar anthropometric and clinical profile compared with the studied group. The majority (61.8%) of the patients with OSA were nonsleepy (ESS score , 10). Patients with OSA had a higher prevalence of obesity, hypertension, diabetes mellitus, and history of atrial fibrillation, whereas current smoking was more common in the non-OSA group. Age, male sex, body mass index, and ESS score, but not comorbidities, were independent predictors of OSA. Conclusions: The occurrence of unrecognized OSA in this revascularized CAD cohort was higher than previously reported. We suggest that OSA should be considered in the secondary prevention protocols in CAD. Keywords: angioplasty; bypass; coronary disease; risk factors; sleep apnea

(Received in original form November 21, 2012; accepted in final form April 29, 2013 ) Supported by grants from the Swedish Research Council (521-2011-537); the Swedish Heart–Lung Foundation (20080592, 20090708, 20100664, and 20120568); the “Agreement concerning Research and Education of Doctors” of Vastra ¨ Gotalandsregionen ¨ (ALFGBG-11538 and ALFGBG-150801); research funds at Skaraborg Hospital (VGSKAS-4731, VGSKAS-5908, VGSKAS-9134, VGSKAS-14781, VGSKAS-40271, and VGSKAS-116431); the Skaraborg Research and Development Council (VGFOUSKB-46371 to H.G.); and the Heart Foundation of Karnsjukhuset, ¨ ResMed Foundation, ResMed Ltd, and ResMed Sweden AB. Author Contributions: H.G., E.T., J.H., J.E., and Y.P. designed research; H.G., E.T., B.C., and Y.P. conducted research; H.G., E.T., S.N., and Y.P. analyzed data; H.G., E.T., J.H., and Y.P. wrote the paper; Y.P. had primary responsibility for final content. All authors read and approved the final manuscript. Correspondence and requests for reprints should be addressed to Yuksel ¨ Peker, M.D., Ph.D., Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska Academy, University of Gothenburg and Sleep Medicine Unit, Skaraborg Hospital, SE 54185 Skovde, ¨ Sweden. E-mail: [email protected] Ann Am Thorac Soc Vol 10, No 4, pp 350–356, Aug 2013 Copyright © 2013 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201211-106OC Internet address: www.atsjournals.org

Obstructive sleep apnea (OSA) and coronary artery disease (CAD) are common health problems (1, 2). OSA is characterized by intermittent episodes of complete or partial upper airway collapse (apnea/ hypopnea) during sleep with large negative oscillations in intrathoracic pressure followed by recurrent hypoxemia (3). OSA 350

is generally defined as five or more apneas– hypopneas per hour of sleep (i.e., the apnea–hypopnea index [AHI]) based on polysomnography (PSG) (4). The classification of OSA severity comprises both the AHI and the degree of daytime sleepiness. Applying a cutoff level of an AHI of 15, regardless of daytime sleepiness,

the OSA prevalence was 9% in men and 4% in women in a middle-aged general population (1). Information regarding the prevalence of OSA in CAD cohorts is unfortunately scarce. In a review, including 11 small studies with a total number of 776 patients, the mean prevalence of OSA was reported to be 42% (5).

AnnalsATS Volume 10 Number 4 | August 2013

ORIGINAL RESEARCH Mechanical revascularization, in terms of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), has been an important task for the health care community (6). Despite the advances in medical treatment and revascularization techniques, the risk of repeat revascularization, myocardial infarction, and cardiovascular mortality is still considerable within the first years after mechanical intervention (7, 8). Among factors contributing to adverse outcomes in these patients, many traditionally recognized risk factors are considered but, to date, OSA is still a neglected condition. In the current cross-sectional report, we aimed to address the occurrence and predictors of OSA among revascularized patients with CAD within the framework of a randomized controlled trial (Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea [RICCADSA]), evaluating the impact of continuous positive airway pressure (CPAP) treatment on cardiovascular outcomes in CAD patients with OSA (9).

Sweden). The trial was registered with ClinicalTrials.gov (NCT 00519597).

Methods

Cardiorespiratory Polygraphy at Home

Study Population

The portable, limited sleep study performed with the Embletta PDS (portable digital system) device (Embla, Broomfield, CO), consisted of the following: (1) nasal pressure detector using nasal cannulas/pressure transducer system, recording the square root of pressure as an index of flow; (2) thoracoabdominal movement detection through two XactTrace inductive belts with respiratory inductive plethysmography (RIP) technology; (3) finger pulse oximeter detecting heart rate and oxyhemoglobin saturation (SpO2); and (4) body position and movement detection. The patient’s sleep time was estimated on the basis of self-reporting as well as the pattern of body movement during the study. Patients with an estimated sleep time of less than 4 hours were offered a new home-based sleep study. Apneas were defined as an almost complete (> 90%) cessation of airflow. Hypopneas were defined as a reduction in thoracoabdominal movement of at least 50% and/or in the nasal pressure amplitude of at least 50% for at least 10 seconds (11). In addition, the total number of significant oxyhemoglobin desaturations (drop by at least 4% from the

The health care system for the management of patients with CAD requiring mechanical revascularization in Skaraborg County, western Sweden has been described in detail elsewhere (9), and the patient log for the RICCADSA trial is illustrated in Figure 1. In brief, all consecutive patients with CAD (n = 1,291) who had newly (, 6 mo) undergone PCI or CABG between September 29, 2005 and November 7, 2010 were asked to participate in the trial via the coronary artery outpatient clinics at the Skaraborg Hospital in Skövde and Lidköping. Anthropometrics and medical history were documented for the whole cohort. Excluding 32 patients with a known OSA diagnosis and treatment, a total number of 1,259 subjects were eligible for the study. Among those, 662 agreed to undergo an ambulatory, polygraphic cardiorespiratory sleep study at home and completed an Epworth Sleepiness Scale (ESS) questionnaire. The study complied with the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of the Medical Faculty of the University of Gothenburg (Gothenburg,

Definition of the Baseline Clinical Characteristics

The baseline anthropometrics, smoking habits, and medical history for the whole population were obtained from the medical records after mechanical revascularization. Body mass index (BMI) was calculated according to the formula body weight divided by height squared, and obesity was defined as a BMI of at least 30 kg/m2 (10). Information regarding known concomitant diseases at baseline, including hypertension and diabetes, was based on self-reported and/or physician-diagnosed conditions. As almost all revascularized patients with CAD were taking lipidlowering medication, regardless of blood lipid values, hyperlipidemia was not considered in the baseline comorbidity evaluation. More detailed information about the severity of the CAD, the angiographic findings, the type of the mechanical intervention (PCI or CABG), as well as the baseline medications was obtained for the cohort undergoing sleep study.

Glantz, Thunstrom, ¨ Herlitz, et al.: Obstructive Sleep Apnea in Coronary Artery Disease

immediately preceding baseline) was scored, and the oxygen desaturation index was calculated as the number of significant desaturations per hour of estimated sleep. Events with a reduction in thoracoabdominal movement of at least 30% and/or in the nasal pressure amplitude of at least 30% for at least 10 seconds were also scored as hypopneas if there was a significant desaturation (> 4%). OSA was defined as an AHI of at least 15 per hour of the total recording time. In case of newly assessed polygraphic investigation with another similar system (Breas SC20; Breas Medical AB, Mölnlycke, Sweden) among patients with CAD who were referred after mechanical revascularization to the sleep medicine unit by cardiologists, unaware of the RICCADSA trial, the baseline recordings were scored according to the given criteria as described previously. All baseline-screening recordings were scored by the same observer (Y.P.). Overnight PSG in Hospital

All CAD patients with an OSA diagnosis on the first screening investigation with the Embletta system underwent unattended overnight PSG in hospital, using a computerized recording system (Embla A10; Embla), for the comparison between sleepy versus nonsleepy OSA phenotypes as one of the secondary analyses (9). The PSG system included sleep monitoring through three-channel electroencephalography (EEG [C4/A1, C3/A2, CZ/A1]), twochannel electrooculography (EOG), onechannel submental electromyography (EMG), bilateral tibial EMG, and two-lead electrocardiography in addition to the cardiorespiratory channels as described previously for the Embletta system. PSG recordings were scored on the basis of 30-second epochs according to the Rechtschaffen and Kales criteria (12) by an observer blinded to the clinical data and baseline screening results from the previous Embletta recordings. Epworth Sleepiness Scale

Excessive subjective daytime sleepiness was assessed by ESS (13), the most widely used index to measure subjective sleepiness in OSA. The ESS consists of eight questions for evaluating the chance of dozing off under eight situations in the past month. Each item is scored from 0 to 3 (0, would never doze; 1, slight chance of dozing; 2, 351

ORIGINAL RESEARCH their 95% CIs. A paired t test was used for comparison of AHI by PG versus PSG for the OSA group included in the randomized controlled trial (RCT) arm. All statistical tests were two-sided, and a P value less than 0.05 was considered significant. Statistical analysis was performed with the Statistical Package for Social Sciences, version 20.0 for the Windows system (SPSS Inc., Chicago, IL).

Results Baseline Clinical Characteristics of the Whole Cohort

In all, 1,291 patients underwent PCI or CABG during the recruitment period (Figure 1). Among them, 32 patients had an already known OSA, of whom 18 were treated with CPAP. Thus, 1,259 patients were eligible for the trial, of whom 662 (52.7%) agreed to participate in the sleep study. As shown in Table 1, the patients with CAD who chose not to participate were slightly older, and the proportion of women as well as that of patients undergoing CABG was higher compared with that in the screened group. However, there were no statistically significant differences between the groups regarding BMI, obesity, current smoking, and comorbidities other than less lung disease, which was more frequent in the screened group. Figure 1. Patient log demonstrating the study cohort and the various subgroups. AHI = apnea– hypopnea index; CABG = coronary artery bypass grafting; CAD = coronary artery disease; CPAP = continuous positive airway pressure; CSA = central sleep apnea; CSR = Cheyne-Stokes respiration; OSA = obstructive sleep apnea; PCI = percutaneous coronary intervention; RICCADSA = Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea.

moderate change of dozing; 3, high chance of dozing). The range of ESS score is from 0 to 24. Excessive daytime sleepiness was defined as the ESS score of at least 10 (9). Group Allocation

Group allocation was based on the results of ambulatory cardiorespiratory polygraphy (PG) and the ESS questionnaire (Figure 1). Statistics

Descriptive statistics are given as means 6 SD and categorical variables as numbers (percentages). The 95% confidence interval (CI) was calculated for prevalence of OSA according to normality approximation. For the baseline cross-sectional variables, differences in means between patients with 352

CAD undergoing sleep study versus no sleep study were analyzed by Student t test, and the chi-squared test was used to compare categorical variables. For comparison of means between OSA, borderline OSA, and non-OSA groups, the one-way analysis of variance test was applied with post-hoc Bonferroni analysis. Moreover, age, sex, BMI, obesity, and comorbid conditions were included in a logistic regression model to test the association with OSA in the cohort. The significant variables that correlated with OSA in the univariate analyses were included in a multivariate logistic regression model, and corrected odds ratios (ORs) were calculated from the regression coefficients. All ORs are presented with

Baseline Clinical Characteristics of the Patients Undergoing Cardiorespiratory Sleep Study

Among the 662 patients (mean age, 64.1 6 8.7; range, 37–83 yr; 15.7% women) undergoing cardiorespiratory PG (659 by Embletta, 3 by Breas SC20), 422 (63.7%; 95% CI, 60.1–67.4%) had OSA according to the given criteria, and 118 patients (17.8%; 95% CI, 14.9–20.7%) did not have OSA. The remaining 101 patients (15.3%; 95% CI, 12.5–18.0%) demonstrated borderline OSA, and 21 (3.2%; 95% CI, 1.8–4.5%) had predominantly CSA/CSR (central sleep apnea/Cheyne-Stokes respiration) (Figure 1). The time interval between the mechanical intervention and cardiorespiratory sleep study ranged between 1 and 176 days (mean interval, 61.0 6 31.8 d). As illustrated in Figure 2, when adding OSA to the traditionally recognized risk factors for CAD, OSA was the most frequent (63.8%) followed in order of frequency by hypertension (56.7%), obesity (25.2%), diabetes mellitus


ORIGINAL RESEARCH Table 1. Demographic and clinical characteristics of entire study population Variable

Age, yr BMI, kg/m2 Obesity, % Male sex, % Current smokers, % Lung disease, % CABG at inclusion, % Hypertension, % Atrial fibrillation, % Diabetes mellitus, % Stroke, % Depression, %

Sleep Study Performed (n = 662) 64.1 6 8.7 28.0 6 4.0 25.2 84.3 20.1 9.1 24.0 56.7 17.9 22.2 7.2 4.9

No Sleep Study (n = 597) 66.8 6 9.2 27.5 6 4.2 22.1 76.9 23.9 5.8 30.8 55.2 18.8 24.4 7.3 3.9

P Value* ,0.001 0.061 0.198 ,0.001 0.117 0.024 0.007 0.592 0.679 0.362 0.951 0.420

Definition of abbreviations: BMI = body mass index; CABG = coronary artery bypass grafting. *Continuous variables are expressed as means 6 SD, statistics by unpaired Student t test. Comparison of groups was done by chi-squared test.

(22.1%), current smoking (20.1%), and pulmonary disease (9.1%). The majority of the patients with OSA (n = 262; 61.2%) were nonsleepy, and 163 patients (24.6% of the entire study population) had severe OSA (AHI > 30/h). Baseline Clinical Characteristics of the Groups

As shown in Table 2, patients with OSA were slightly older, included more men, and had a higher prevalence of obesity, hypertension, diabetes, and history of atrial fibrillation than the patients with borderline OSA and patients without OSA, whereas current smoking was more common in the

non-OSA group. There were no significant differences between the groups regarding other comorbidities. The use of b-blocking agents, diuretics, and calcium channel as well as angiotensin II antagonists was more common among the patients with OSA compared with the non-OSA group (post-hoc Bonferroni analysis). Angiotensin-converting enzyme inhibitors and lipid-lowering agents did not differ significantly between the groups. Regarding the anticoagulants, warfarin use was more common among the patients with OSA, and aspirin/clopidogrel use was more common in the non-OSA group (Table 2).

Figure 2. Occurrence of obstructive sleep apnea and the traditionally recognized risk indicators for coronary artery disease. OSA = obstructive sleep apnea.


As shown in Table 3, univariate variables associated with OSA in this cohort were age, male sex, BMI, obesity, ESS score, excessive daytime sleepiness, hypertension, and diabetes, whereas current smoking was inversely correlated with OSA. In a multivariate logistic regression analysis, age, male sex, BMI, and ESS score were significantly related with OSA, but hypertension and diabetes mellitus were not; the inverse relationship between current smoking and OSA was not significant in multivariate. Overnight PSG

All patients with OSA (n = 399) underwent unattended overnight PSG in hospital 5 to 146 days after the baseline cardiorespiratory PG (mean interval, 34.9 6 23.0 d). Five PSG recordings were not valid because of technical failure. For the remaining 394 patients, the mean total sleep time was 380.6 6 92.3 minutes, recorded by the PSG device, and the mean estimated total sleep time was 420.9 6 64.8 minutes, recorded by the cardiorespiratory PG (P , 0.001). The mean AHI values were 40.6 6 23.4/hour by PSG and 29.9 6 14.6/hour by PG (P , 0.001).

Discussion We found that among revascularized patients with CAD, unrecognized OSA was highly prevalent, and the majority of these patients did not report daytime sleepiness. Overall, two-thirds of these patients had OSA, which was higher than other known risk indicators for CAD such as hypertension, diabetes, and current smoking in this cohort. Moreover, patients with OSA demonstrated a more severe comorbidity profile as compared with CAD patients without OSA. In a review (5) including 11 small studies with a total number of 776 patients with CAD, the mean prevalence of OSA defined as an AHI of at least 10/hour was 42%, the majority based on PSG. Regarding the mechanically revascularized patients with CAD, Yumino and coworkers found OSA among 57% of 89 consecutive patients with acute coronary syndrome, treated by PCI (14). The cutoff value of AHI was chosen as 10/hour for OSA diagnosis in that cohort, based on a cardiorespiratory PG. Thus, the prevalence of OSA was much higher in our cohort than previously reported among the patients with CAD, although a higher cutoff level (AHI > 15/h) was used. 353

ORIGINAL RESEARCH Table 2. Characteristics of study population undergoing overnight sleep recording Variable

Age, yr AHI, no./h ODI, no./h ESS score BMI, kg/m2 Obesity, % Male sex, % Current smokers, % Lung disease, % CABG at inclusion, % Hypertension, % Atrial fibrillation, % Diabetes mellitus, % Stroke, % Depression, % Medications b-Blockers, % Diuretics, % Calcium antagonists, % ACE inhibitors, % AT2 antagonists, % Lipid-lowering agents, % Aspirin, % Clopidogrel, % Warfarin, % SSRI, %

OSA (n = 422)

Borderline OSA (n = 101)

64.6 6 8.2 29.8 6 14.4 17.9 6 13.9 8.1 6 4.1 28.9 6 4.0 33.2 86.3 17.6 8.3 26.8 61.6 19.2 25.4 7.9 5.2

62.9 6 8.2 8.9 6 2.1 4.3 6 2.0 7.4 6 3.8 26.9 6 3.9 14.9 84.2 23.2 7.1 23.8 49.5 18.6 16.3 5.2 4.1

90.3 22.0 20.2 43.8 14.8 94.9 88.6 57.2 8.8 5.4

84.5 14.4 17.5 40.2 10.3 96.9 96.9 67.0 3.1 3.1

Non-OSA (n = 118)

6 9.6 6 1.3 6 1.3 6 2.9 6 3.0 6.8 77.1 27.7 12 7 16.9 47.5 10.3 14.4 6.8 5.3

61.7 3.0 1.6 5.7 25.5

79.5 9.9 11.6 39.3 7.1 90.1 96.4 69.6 2.7 4.5

P Value* 0.002 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 0.055 0.050 0.266 0.088 0.006 0.081 0.013 0.636 0.907 0.006 0.008 0.111 0.618 0.070 0.076 0.003 0.024 0.022 0.647

Definition of abbreviations: ACE = angiotensin-converting enzyme; AHI = apnea–hypopnea index; AT2 = angiotensin II; BMI = body mass index; CABG = coronary artery bypass grafting; ESS = Epworth Sleepiness Scale; ODI = oxygen desaturation index; OSA = obstructive sleep apnea; SSRI = selective serotonin reuptake inhibitor. *Continuous variables are expressed as means 6 SD, statistics by unpaired Student t test. Comparison of groups was done by one-way analysis of variance with post hoc Bonferroni analysis.

The cardiovascular risk indicators such as obesity, hypertension, and diabetes were more prevalent among patients with CAD and OSA compared with patients with CAD without OSA. Moreover, CABG as well as a history of atrial fibrillation was more common, and the use of cardiovascular drugs was significantly higher among the patients with OSA, reflecting a more severe CAD profile. It should be emphasized that the patients without OSA were not a healthy control group, as they all had CAD, and current smoking was more common in the non-OSA group compared with the subjects with OSA. We found that age, male sex, BMI, and excessive daytime sleepiness were independently associated with a high prevalence of OSA. This is in agreement with results from studies in the general population and sleep clinic cohorts (1). The relationship between OSA and hypertension as well as diabetes seems to be of limited importance in a multivariate model among patients with already established CAD. 354

The major limitation of the current report is that nearly half of the patients with CAD who were eligible for the sleep study chose not to participate. The main reasons for declining were long journeys, in-hospital procedures, and lack of sleep complaints, or being too tired after the mechanical revascularization. Lack of sleep complaints might be interpreted as low probability of having OSA. However, this seems not to be the case for patients with CAD, as almost two-thirds of the OSA group did not report significant sleep complaints. Indeed, subjective tiredness after the mechanical revascularization might also mask excessive daytime sleepiness and symptomatic OSA. As there were no statistically significant differences between the screened and nonscreened groups regarding BMI, obesity, current smoking, and comorbidities other than less prevalent lung disease in the screened group, we think that our sleep study cohort was relatively representative of the revascularized patients with CAD during the inclusion period in

this region. Another limitation was the group allocation, which was based on cardiorespiratory sleep studies in comparison with PSG. However, the cutoff value for AHI (15/h) chosen for OSA diagnosis was previously shown to be reliable for the Embletta system (15) used in the current trial. The subjects with AHI 5.0–14.9, here described as borderline OSA, can therefore also be defined as patients with mild OSA (16). These subjects were handled according to the clinical routines and were not included in the RCT arm. Although we had PSG recordings before the start of RCT in the protocol, this was mainly planned for the further evaluation of sleepy versus nonsleepy OSA phenotypes. As the scoring of the PSGs was done subsequently during the follow-up period by an independent observer blinded to the baseline PG results, we chose not to redefine the group allocation. The differences in the absolute AHI values may reflect night-to-night variability, the range of the time interval


ORIGINAL RESEARCH Table 3. Baseline variables associated with obstructive sleep apnea in study population*

Univariate analysis Age Male sex BMI Obesity Current smoking ESS Excessive daytime sleepiness Hypertension Diabetes mellitus Multivariate analysis Age Male sex BMI Current smoking ESS Hypertension Diabetes mellitus

OR

95% CI

P Value

1.02 1.53 1.23 4.23 0.62 1.12 3.57 1.71 1.89

1.00–1.04 0.99–2.37 1.17–1.30 2.63–6.81 0.42–0.93 1.07–1.17 2.34–5.45 1.23–2.39 1.23–2.91

0.035 0.053 ,0.001 ,0.001 0.022 ,0.001 ,0.001 0.001 0.004

1.06 1.89 1.24 0.91 1.10 1.29 1.21

1.03–1.08 1.12–3.18 1.17–1.32 0.56–1.46 1.04–1.16 0.88–1.89 0.73–2.00

0.000 0.018 0.000 0.687 0.001 0.192 0.463

Definition of abbreviations: BMI = body mass index; CI = confidence interval; ESS = Epworth Sleepiness Scale; OR = odds ratio; OSA = obstructive sleep apnea. *Study population: n = 641.

between baseline PG and PSG investigations, the difference between total sleep time by PSG and the estimated total sleep time by PG, as well as the definition of hypopneas by PSG versus cardiorespiratory PG. One might also argue that there was a lack of a control group without CAD, which could have given us information on the relative increase in OSA in our study population. However, in a previous case– control study from the same county, the prevalence of OSA was 12.9% among the otherwise healthy subjects individually matched for age, sex, and BMI with the patients with CAD (17). On the basis of the cardiorespiratory PG recordings, we found that two-thirds of the patients had OSA. It should be noted that the primary aim of this trial was not to

evaluate the prevalence of OSA but to address the impact of CPAP treatment on cardiovascular outcomes in a revascularized CAD cohort. In other words, there might be an overrepresentation of subjects with snoring, which is a common symptom of OSA. However, all patients were informed that participation and follow-up were available even for those patients not having OSA. About one-third of patients with OSA in this CAD cohort had excessive daytime sleepiness as defined by an ESS score of at least 10. As compared with the general population, this number is relatively high but still low compared with the sleep clinic cohorts (16). It might also be argued that the Multiple Sleep Latency Test (18), which is commonly used as an objective sleepiness test in well-established sleep clinics, would

References 1 Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230–1235. 2 Smith SC Jr, Benjamin EJ, Bonow RO, Braun LT, Creager MA, Franklin BA, Gibbons RJ, Grundy SM, Hiratzka LF, Jones DW, et al. AHA/ ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. J Am Coll Cardiol 2011;58:2432–2446.

be more accurate in classifying sleepy versus nonsleepy patients with OSA. However, this test is time-consuming and not feasible to run for large-scale cardiac populations. Both OSA and CAD are common health problems, and mechanical revascularization has been an important task for the health care community (6). Among factors contributing to adverse outcomes in these patients, traditionally recognized risk factors are considered, but OSA is still a neglected condition in the literature, except in a few studies (14, 19). However, as also stated by the American Heart Association/American College of Cardiology, there is a paucity of data for a causal role of OSA in adverse outcomes in cardiac patients (20). In this context, our baseline report, suggesting that OSA is more prevalent than hypertension, obesity, diabetes, and current smoking among revascularized patients with CAD, is of clinical importance. OSA is a treatable condition but only few are considered for diagnostic investigation for OSA and subsequent treatment with CPAP, as also illustrated in this entire population (Figure 1). In summary, there seem to be enough data from this cross-sectional report for cardiologists to at least consider OSA as a confounding factor in studies addressing the impact of various treatment protocols such as lipidlowering agents and bare-metal versus drug-eluting stents in revascularized CAD cohorts. We believe that the cardiology field should consider the screening of CAD patients with regard to OSA, and enter OSA into the secondary prevention models. n Author disclosures are available with the text of this article at www.atsjournals.org.

3 Turgut Celen Y, Peker Y. Cardiovascular consequences of sleep apnea. II. Cardiovascular mechanisms. Anadolu Kardiyol Derg 2010;10:168–175. 4 American Academy of Sleep Medicine (AASM). International classification of sleep disorders. Westchester, PA: AASM; 2005. 5 Hedner J, Franklin K, Peker Y. Coronary artery disease and sleep apnea. In: Kryger MH, Roth TT, Dement WT, editors. Principles and practice of sleep medicine, 5th ed. Philadelphia, PA: Elsevier; 2011. pp. 1393–1399. 6 Bravata DM, Gienger AL, McDonald KM, Sundaram V, Perez MV, Varghese R, Kapoor JR, Ardehali R, Owens DK, Hlatky MA. Systematic review: the comparative effectiveness of percutaneous coronary interventions and coronary artery bypass graft surgery. Ann Intern Med 2007;147:703–716.


355

ORIGINAL RESEARCH 7 Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Stahle ˚ E, Feldman TE, van den Brand M, Bass EJ, et al.; SYNTAX Investigators. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961–972. 8 Kappetein AP, Feldman TE, Mack MJ, Morice MC, Holmes DR, Stahle ˚ E, Dawkins KD, Mohr FW, Serruys PW, Colombo A. Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial. Eur Heart J 2011;32:2125–2134. 9 Peker Y, Glantz H, Thunstrom ¨ E, Kallryd A, Herlitz J, Ejdeback ¨ J. Rationale and design of the Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnoea—RICCADSA trial. Scand Cardiovasc J 2009;43:24–31. 10 National Heart, Lung, and Blood Institute, National Institutes of Health. Clinical Guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. Obes Res 1998;6:51S–209S. 11 American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22:667–689. 12 Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Bethesda, MD: U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health; 1968. 13 Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991;14:540–545.

356

14 Yumino D, Tsurumi Y, Takagi A, Suzuki K, Kasanuki H. Impact of obstructive sleep apnea on clinical and angiographic outcomes following percutaneous coronary intervention in patients with acute coronary syndrome. Am J Cardiol 2007;99:26–30. 15 Dingli K, Coleman EL, Vennelle M, Finch SP, Wraith PK, Mackay TW, Douglas NJ. Evaluation of a portable device for diagnosing the sleep apnoea/hypopnoea syndrome. Eur Respir J 2003;21: 253–259. 16 Celen YT, Peker Y. Cardiovascular consequences of sleep apnea. I. Epidemiology. Anadolu Kardiyol Derg 2010;10:75–80. ˚ Bende M. An 17 Peker Y, Kraiczi H, Hedner J, Loth ¨ S, Johansson A, independent association between obstructive sleep apnoea and coronary artery disease. Eur Respir J 1999;14:179–184. 18 Wise MS. Objective measures of sleepiness and wakefulness: application to the real world? J Clin Neurophysiol 2006;23:39–49. 19 Cassar A, Morgenthaler TI, Lennon RJ, Rihal CS, Lerman A. Treatment of obstructive sleep apnea is associated with decreased cardiac death after percutaneous coronary intervention. J Am Coll Cardiol 2007;50:1310–1314. 20 Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, et al. Sleep apnea and cardiovascular disease. An American Heart Association/ American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing Council. Circulation 2008;118: 1080–1111.
