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(Chest. 2005;127:66-71.)
© 2005 American College of Chest Physicians

Accuracy of Monitoring for Sleep-Related Breathing Disorders in the Coronary Care Unit*

Margot A. Skinner, MPhEd; Mahbubur S. Choudhury, MB ChB; Sean D.R. Homan, MSc; Jan O. Cowan, MB ChB; Gerard T. Wilkins, MB ChB and D. Robin Taylor, MD

* From the Department of Medical and Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

Correspondence to: D. Robin Taylor, MD, Department of Medicine, Dunedin School of Medicine, PO Box 913, Dunedin, New Zealand; e-mail: robin.taylor{at}stonebow.otago.ac.nz


   Abstract
TOP
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
Study objectives: To evaluate the frequency of sleep-disordered breathing (SDB) in patients presenting with acute cardiovascular events.

Design: Repeat observational study.

Setting: Coronary care unit of a university hospital.

Patients: A total of 26 patients presenting with unstable angina, myocardial infarction, or left ventricular failure.

Measurements: Level 3 portable sleep study performed at the time of acute presentation (study 1; 26 patients) and again ≥ 6 weeks later (study 2; 18 patients).

Results: SDB (apnea-hypopnea index ≥ 15) was identified in 13 of 26 patients (50%) during study 1. One patient had central sleep apnea. Of the 18 who completed the two studies, SDB was confirmed in 10 of 18 patients (56%) during study 1 but in only 5 of 18 patients (28%) during study 2. All five of those patients had obstructive sleep apnea (OSA). Six patients were deemed to have false-positive results for SDB at follow-up, and one patient was deemed to have a false-negative result. Detailed analysis suggested that supine posture during study 1 may have contributed to the high false-positive rate, even though only three of six patients fulfilled the criteria for positional OSA.

Conclusions: SDB occurs commonly in patients presenting with an acute cardiovascular event. Consideration of the diagnosis of SDB is an important strategy for secondary prevention. However, our findings indicate that SDB abnormalities may be transient. Sleep studies to investigate SDB as a potential risk factor for cardiovascular morbidity should be carried out when the patient is clinically stable.

Key Words: cardiovascular risk • portable sleep monitoring • sleep apnea • sleep-disordered breathing


   Introduction
TOP
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
The relationship between obstructive sleep apnea (OSA) and cardiovascular disease is complex. Epidemiologic evidence indicates that OSA is an independent risk factor for cardiovascular morbidity.1 The prevalence of hypertension is increased in subjects with OSA in a dose-dependent manner.234 Similarly, the incidence of ischemic heart disease is increased with OSA, although the effect is more modest.5 Conversely, OSA is more common in stable patients presenting with ischemic heart disease6 and acute myocardial infarction (MI).7 More importantly, long-term outcomes following MI are worse in those who have OSA.78 For all of these reasons, making the diagnosis of OSA in patients with cardiovascular disease is important, particularly given that adequate management improves the control of BP,910 the prognosis for patients with congestive cardiac failure,1112 and the overall long-term mortality rate.13

In the acute clinical setting, there is a dynamic interaction between sleep-disordered breathing (SDB) and cardiovascular function. Apneic events result in increased sympathetic nervous system activity, increased systemic BP, reduced myocardial oxygen delivery, and decreased cardiac output.14 Even in healthy patients, ST-segment changes may be observed in association with prolonged apneas.15 There is a strong relationship between SDB and left ventricular dysfunction,16 probably because the hemodynamic consequences of obstructive apneas cause increased demand on the left ventricle.14 Patients with left ventricular dysfunction are more at risk for serious ventricular arrhythmias, although evidence for life-threatening arrhythmias with OSA is rather scant.17 On the other hand, left ventricular dysfunction is itself associated with abnormal breathing. Cheyne-Stokes respiration/central sleep apnea (CSA) occur in up to 40% of patients with congestive cardiac failure.18 This adds further complexity to the interpretation of any abnormal breathing that may be observed in patients with unstable cardiovascular function.

Against this background, there is a need for increased awareness of sleep apnea in patients presenting with acute cardiovascular illness. The possibility of OSA as a treatable risk factor may not previously have been considered. Even where it has, facilities for the adequate investigation of OSA are often extremely limited. Discharging a patient from the hospital with acute cardiovascular illness without a definitive diagnosis will delay appropriate intervention, and so the possibility of confirming OSA promptly would be an advantage. Recently, a reliable portable monitoring device that is suitable for the diagnosis of SDB outside the sleep laboratory has become available.19 Using this approach, we aimed to identify the frequency of OSA and other sleep-related breathing disorders in consecutive patients who were admitted to a coronary care unit (CCU). We reasoned that this would provide the basis for improved overall care by identifying and treating an important risk factor in a high-risk group of patients.


   Patients and Methods
TOP
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Consecutive patients admitted to the Coronary Care Unit of Dunedin Hospital between April 1 and May 31, 2003, were invited to participate as soon as their clinical status had been satisfactorily stabilized. Inclusion criteria were as follows: diagnosis of unstable angina; acute MI; and left ventricular or congestive cardiac failure. Exclusion criteria were as follows: known diagnosis of OSA or other sleep-related disorder; or requiring ongoing supplementary oxygen therapy at the time of the proposed sleep study (this precluded airflow measurements using thermistors). All patients completed the Epworth sleepiness scale (ESS) questionnaire.20 Height and weight were recorded.

Two overnight sleep studies were performed. The first was carried out in the CCU or in the adjacent cardiology ward using a portable diagnostic device (Embletta; Flaga Medical Devices; Reykjavik, Iceland). The device is suitable for use both in hospital and at home, and it has been validated against full polysomnography.19 In that investigation, the apnea-hypopnea index (AHI) per hour in bed differed on average by a mean (± SD) of 3 ± 9 events per hour from the AHI per hour in bed that was obtained from a synchronous full polysomnography, with an overall tendency for the underestimation of AHI using the portable diagnostic device. The parameters measured were as follows: nasal and oral airflow using two appropriately placed thermistors; thoracoabdominal movements via two piezoelectric bands; pulse oximetry using a finger probe; snoring episodes detected via a vibration sensor placed anterior to the sternomastoid muscle; and continuous actigraphy to monitor and record body position. In cases in which narcotic analgesics, sedatives, or hypnotic drugs had been used during the previous 12 h, the study was deferred until these were no longer required for at least 12 h. A second identical overnight study was performed in the patient’s home at least 6 weeks after discharge from the hospital or, if necessary, at a later time when the patient’s clinical status was deemed to be stable. This was to confirm the repeatability of the findings obtained during the hospital-based study.

Outputs from the portable diagnostic device were scored manually by two sleep laboratory technicians without knowledge of the clinical characteristics of the patient. Using the manually scored data, the AHI (events per hour) was computed using a computer program (Somnologica; Flaga Medical Devices). Apneas were defined as the complete cessation of airflow, and hypopneas were defined as a reduction in thoracoabdominal movement of > 50%, each for ≥ 10 s. Central and obstructive apneas were distinguished by the presence or absence of thoracoabdominal movements during an apnea. The AHI was calculated as the number of respiratory events per hour of recording time in bed, with the start of recording being the point at which respiration settled to a rhythmic, stable pattern. The end of the recording time was either the waking time recorded by the subject or the point at which the thoracoabdominal tracings became disturbed, which was consistent with wakefulness. An AHI of ≥ 15 events per hour was considered to be clinically significant.21

The sleep habits, daytime sleepiness, activity, snore symptoms, general health, and medication use for the subject were recorded using standardized questionnaires including the following: the ESS20; the functional outcomes of sleep questionnaire22; the Medical Outcomes Study 36-item short form23; and the Scottish Sleep Health Survey.24 The questionnaires were administered at the time of enrollment into the study and were repeated in those subjects who underwent a second study.

The study was approved by the Otago Ethics Committee, and each patient gave written informed consent. At the end of the study, individual results were communicated to each patient and, where appropriate, treatment was offered.

Statistical Analysis
Descriptive statistics were obtained for each of the primary end points and are reported as group means with SDs or ranges. The t tests and {chi}2 test were used where appropriate.


   Results
TOP
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
There were 101 admissions to the CCU during the designated study period, of which 41 met the diagnostic criteria for inclusion in the study. Twelve patients declined to participate. Twenty-nine patients underwent the first sleep study (study 1), but complete data were available for only 26 patients. The remaining three patients were either intolerant of monitoring procedures2 or experienced chest pain during the study night.1 The final CCU admission diagnosis was MI in 14 patients (complicated by left ventricular failure in 2 patients), unstable angina in 11 patients, and isolated left ventricular failure in only 1 patient. The second sleep study (study 2) was carried out in 18 patients (69%) after a mean interval of 74 ± 5 days (range, 38 to 106 days). Of those eight patients who withdrew between the first and second studies, two patients were deceased, two were unwell with unrelated illnesses, and three declined to participate further, indicating that they had no problems with sleep. One subject was unavailable for follow-up.

The demographic details for the study population at entry are shown in Table 1 . Fifteen of the 26 patients (58%) had a history of hypertension. SDB (ie, AHI, ≥ 15) was identified in 13 of 26 patients (50%) at the time of study 1. These figures were even greater using less rigorous criteria to define SDB (Table 2 ). A diagnosis of OSA was made in 12 patients (46%). One patient had CSA. Following study 2, the diagnosis of SDB was confirmed in only 5 of 18 patients (28%); all 5 patients had OSA. Six of the 18 patients (33%) in whom SDB was diagnosed during study 1 were shown not to have SDB at study 2 (Table 3 ). One patient with a negative result during study 1 received a diagnosis of SDB during study 2. Among those six patients who had a false-positive result in study 1, the mean percentage of time spent in the supine position fell significantly between the study 1 and study 2 (p = 0.019). However, only three of these six patients met the formal criteria for a diagnosis of positional OSA during study 1.25 Detailed sleep study data for the 18 patients who completed both studies are contained in Table 2. In these 18 patients, the mean percentage of time spent in the supine position fell from 33.1 ± 25.0% to 19.2 ± 17.9% (difference not significant).


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  		Table 1.. Demographic Details*

 

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  		Table 2.. Sleep Study Data Obtained Immediately After Study 1 and Study 2

 

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  		Table 3.. Sleep Study Data Obtained From Six Patients With False-Positive Results Who Completed Two Studies and Fulfilled Criteria for SDB at Study 1 but not at Study 2*

 
Clinical follow-up was arranged for all patients with SDB confirmed at study 2. Two patients received treatment with continuous positive airway pressure, and in the remainder it was recommended that continuous positive airway pressure should be commenced in the future either if the patient’s cardiac status deteriorated, if hypertension became difficult to stabilize, or if daytime hypersomnolence developed.

An analysis of the results for ESS scores did not reveal any consistent relationship between the ESS score and the AHI. Only 4 of 26 patients (16%) with a diagnosis of SDB during study 1 had an ESS score of ≥ 10. Outcomes from the other standardized questionnaires were unremarkable apart from the Medical Outcomes Study 36-item short form mental health scores that were obtained during study 2, which were consistent with the results obtained with MI.23


   Discussion
TOP
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
The results of this observational study confirm that SDB is common in a highly selected group of at-risk patients who are admitted to the CCU. Using very conservative criteria for diagnosis, 12 patients (46%) were shown to have OSA and 1 had CSA at the time of their acute presentation. However, the results of the follow-up investigation showed that in a significant number of patients, the findings were transient and could not be repeated. A final diagnosis of SDB was confirmed in 5 of 26 patients (19% of the original study group). Using less stringent criteria (ie, AHI, ≥ 5), these figures were significantly greater, as follows: 19 of 26 patients (73%) at baseline qualified for a diagnosis of SDB; and 15 of 18 patients (83%) on the repeat study night qualified for a diagnosis of SDB. Given the high prevalence of SDB using these latter thresholds, it is probably wiser to arrive at a diagnosis and to offer treatment based on the more rigorous criteria.

Our results have important practical implications. Identifying and treating risk factors that are known to influence long-term outcomes in patients with cardiovascular disease are important aspects of secondary prevention. Arguably, this should be done as early as possible when patients are in contact with clinical staff whose awareness of these risk factors is high and in a setting where facilities for prompt investigation are more likely to be available. However, based on our findings, attempting to diagnose SDB early in patients with acute cardiovascular presentations should be approached with caution. Our results indicate that casual observations made in the acute setting by clinical staff need not necessarily be indicative of an ongoing problem, and performing sleep studies shortly after admission to the CCU may be wasteful of very limited resources, given the high rate of false-positive diagnoses (6 of 18 diagnoses; 33%).

There are a number of possible reasons for the high false-positive diagnosis rate (ie, patients with either a truly false-positive diagnosis or alternatively patients who have transient SDB for whatever reason). First, acute cardiovascular pathology may itself result in abnormal breathing during sleep, notably with a tendency to central apnea events. Overall, our results did not indicate a significant change in the frequency of central apneas (18 apneas), but in the group of patients who were deemed to have a false-positive diagnoses, the mean frequency of central apnea events fell from 12.5 ± 21.0 to 1.2 ± 2.3 events per hour (difference not significant). An alternative explanation is that patients are more likely to lie supine in the CCU setting compared to their own home because of the need for additional instrumentation (eg, ECG leads). In those subjects with a positive diagnosis at the time of study 1, the time spent in the supine position in the CCU study was significantly greater than that during the later domiciliary study (study 2) [Table 3]. Certain drugs (eg, narcotic analgesics and hypnotic/anxiolytic agents) may affect breathing while asleep, and these are commonly used in the CCU. As far as possible, every effort was made in our study to control for this possible confounder, but it remains possible that the transient SDB was drug-related. Last, the effects of sleep deprivation and/or fragmented sleep on the first night of CCU admission may have resulted in rapid eye movement rebound and a potential increase in recorded respiratory events on the subsequent study night in some patients. This could not be assessed fully in our study with only limited monitoring.

The frequency of SDB in our study population (AHI ≥ 15 at the acute stage, 13 of 26 patients [50%]; AHI ≥ 15 at follow-up, 5 of 18 patients [28%]) is similar to that reported elsewhere among high-risk patients.17262728 In the report by Mooe et al,17 37% of patients with severe angina pectoris had an AHI of ≥ 5 events per hour. Earlier, Saito et al27 reported that 100% of 49 patients with acute MI had apneas, and Hung et al26 reported that 36% of male patients studied within 1 to 8 weeks following an MI had OSA. In these earlier studies, the exact timing of investigation in relation to cardiac events and/or coronary angiography was either not stated,26 was variable,28 or occurred within 6 days of hospital discharge.27 Thus, the validity of the findings in these investigations is not known, and for reasons that are similar to our own study, it may be that either transient SDB or a false-positive diagnosis was being reported. The apparently high prevalence of SDB in each of these studies comprising patients with cardiovascular disease, including the present one, is higher than that in the "normal" population.29 However, this may also be a function of age. Only nine of our patients were aged < 65 years, and it is known that in persons who are > 65 years of age the frequency of SDB ranges from 24 to 42%.3031

In conclusion, SDB occurs commonly in patients presenting with an acute cardiovascular event, and considering the diagnosis of SDB in patients in this high-risk group is an important strategy for secondary prevention. However, our findings indicate that, when investigated in the short term, sleep-related breathing abnormalities are often transient. For this reason, sleep studies to investigate SDB as a potential risk factor for cardiovascular morbidity should be carried out when the patient is clinically stable.


   Acknowledgements
 
We are grateful to ResMed Ltd (North Ryde, NSW, Australia) for providing the Embletta recording equipment for the duration of the study.


   Footnotes
 
Abbreviations: AHI = apnea-hypopnea index; CCU = coronary care unit; CSA = central sleep apnea; ESS = Epworth sleepiness scale; MI = myocardial infarction; OSA = obstructive sleep apnea; SDB = sleep-disordered breathing

The study was supported by the Otago Respiratory Research Trust and the Dunedin Heart Unit Trust.

Received for publication March 11, 2004. Accepted for publication July 22, 2004.


   References
TOP
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Shamsuzzaman, AS, Gersh, BJ, Somers, VK (2003) Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 290,1906-1914[Abstract/Free Full Text]
  2. Nieto, FJ, Young, TB, Lind, BK, et al Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study: Sleep Heart Health Study. JAMA 2000;283,1829-1836[Abstract/Free Full Text]
  3. Peppard, PE, Young, T, Palta, M, et al Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342,1378-1384[Abstract/Free Full Text]
  4. Young, T, Peppard, P Sleep-disordered breathing and cardiovascular disease: epidemiologic evidence for a relationship. Sleep 2000;23,S122-S126[ISI][Medline]
  5. Shahar, E, Whitney, CW, Redline, S, et al Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 2001;163,19-25[Abstract/Free Full Text]
  6. Hayashi, M, Fujimoto, K, Urushibata, K, et al Nocturnal oxygen desaturation correlates with the severity of coronary atherosclerosis in coronary artery disease. Chest 2003;124,936-941[CrossRef][ISI][Medline]
  7. Peker, Y, Hedner, J, Kraiczi, H, et al Respiratory disturbance index: an independent predictor of mortality in coronary artery disease. Am J Respir Crit Care Med 2000;162,81-86[Abstract/Free Full Text]
  8. Mooe, T, Franklin, KA, Holmstrom, K, et al Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med 2001;164,1910-1913[Abstract/Free Full Text]
  9. Logan, AG, Tkacova, R, Perlikowski, SM, et al Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex. Eur Respir J 2003;21,241-247[Abstract/Free Full Text]
  10. Hla, KM, Skatrud, JB, Finn, L, et al The effect of correction of sleep-disordered breathing on BP in untreated hypertension. Chest 2002;122,1125-1132[CrossRef][ISI][Medline]
  11. Sin, DD, Logan, AG, Fitzgerald, FS, et al Effects of continuous positive airway pressure on cardiovascular outcomes in heart failure patients with and without Cheyne-Stokes respiration. Circulation 2000;102,61-66[Abstract/Free Full Text]
  12. Kaneko, Y, Floras, JS, Usui, K, et al Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 2003;348,1233-1241[Abstract/Free Full Text]
  13. He, J, Kryger, MH, Zorick, FJ, et al Mortality and apnea index in obstructive sleep apnea: experience in 385 male patients. Chest 1988;94,9-14[CrossRef][ISI][Medline]
  14. Leung, RS, Bradley, TD Sleep apnea and cardiovascular disease. Am J Respir Crit Care Med 2001;164,2147-2165[Free Full Text]
  15. Hanly, P, Sasson, Z, Zuberi, N, et al ST-segment depression during sleep in obstructive sleep apnea. Am J Cardiol 1993;71,1341-1345[CrossRef][ISI][Medline]
  16. Fung, JW, Li, TS, Choy, DK, et al Severe obstructive sleep apnea is associated with left ventricular diastolic dysfunction. Chest 2002;121,422-429[CrossRef][ISI][Medline]
  17. Mooe, T, Franklin, KA, Wiklund, U, et al Cardiac rhythm in patients with sleep-disordered breathing and coronary artery disease. Scand Cardiovasc J 2000;34,272-276[Medline]
  18. Sin, DD, Fitzgerald, F, Parker, JD, et al Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med 1999;160,1101-1106[Abstract/Free Full Text]
  19. Dingli, K, Coleman, EL, Vennelle, M, et al Evaluation of a portable device for diagnosing the sleep apnoea/hypopnoea syndrome. Eur Respir J 2003;21,253-259[Abstract/Free Full Text]
  20. Johns, MW A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14,540-545[ISI][Medline]
  21. Engleman, HM, Martin, SE, Kingshott, RN, et al Randomised placebo controlled trial of daytime function after continuous positive airway pressure (CPAP) therapy for the sleep apnoea/hypopnoea syndrome. Thorax 1998;53,341-345[Abstract/Free Full Text]
  22. Weaver, TE, Laizner, AM, Evans, LK, et al An instrument to measure functional status outcomes for disorders of excessive sleepiness. Sleep 1997;20,835-843[ISI][Medline]
  23. Ware, JE, Jr, Sherbourne, CD The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992;30,473-483[ISI][Medline]
  24. Engleman, HM, Kingshott, RN, Wraith, PK, et al Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1999;159,461-467[Abstract/Free Full Text]
  25. Cartwright, RD Effect of sleep position on sleep apnea severity. Sleep 1984;7,110-114[ISI][Medline]
  26. Hung, J, Whitford, EG, Parsons, RW, et al Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336,261-264[CrossRef][ISI][Medline]
  27. Saito, T, Yoshikawa, T, Sakamoto, Y, et al Sleep apnea in patients with acute myocardial infarction. Crit Care Med 1991;19,938-941[ISI][Medline]
  28. Mooe, T, Franklin, KA, Wiklund, U, et al Sleep-disordered breathing and myocardial ischemia in patients with coronary artery disease. Chest 2000;117,1597-1602[Medline]
  29. Young, T, Palta, M, Dempsey, J, et al The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328,1230-1235[Abstract/Free Full Text]
  30. Ancoli-Israel, S, Kripke, DF Prevalent sleep problems in the aged. Biofeedback Self Regul 1991;16,349-359[CrossRef][ISI][Medline]
  31. Partinen, M, Telakivi, T Epidemiology of obstructive sleep apnea syndrome. Sleep 1992;15,S1-S4[ISI][Medline]



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TIME-COURSE OF SLEEP DISORDERED BREATHING IN PATIENTS WITH ACUTE CORONARY SYNDROMES
Ahmed S BaHammam, FRCP, FCCP, et al.
Chest Online, 26 May 2005 [Full text]
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