Sleep Apnea and the Heart—the Singapore Experience
Epidemiology and CV Impact of Obstructive Sleep Apnea (OSA)
Singapore is a Southeast Asian country with a population of 5.3 million people, comprising predominantly of Chinese, Malay and Indian ethnic groups. Obstructive sleep apnea (OSA), a sleep breathing disorder characterized by recurrent upper airway collapse, is estimated to be prevalent in up to 15% of the Singapore general population.1 This estimate is significantly higher than the 1-5% prevalence estimates of OSA in Western populations.2
OSA is predominant in middle-aged, overweight Singaporean males, with the majority having moderate-to-severe OSA (AHI≥15). Similar to other Asian populations, it is observed that in Singapore, obesity is a relatively weaker risk factor for OSA compared to Caucasian populations.3 Taken together with the comparatively higher prevalence of OSA, it is hypothesized that local craniofacial characteristics, which may result in an anatomically narrow airway and a higher percentage of body fat, are important features in the increased predisposition of OSA in Asians.3
OSA has gained recognition as an important health concern in Singapore. The pathophysiological mechanisms of OSA, including oxidative stress, inflammation, hypercoagulability and endothelial dysfunction predispose patients with OSA to cardiovascular disease. It is established that untreated OSA is an independent predictor of future cardiovascular morbidities and mortality.4, 5 Of particular significance are the results from the Sleep heart health study, reporting OSA as a significant predictor of future major adverse cardiovascular events.6 The prevalence of OSA in patients with existing cardiovascular disease have been reported to be much higher than the general population. Existing studies report a 26% prevalence among coronary artery disease patients in Singapore who are at high risk of OSA.7 There is a need for a deeper understanding of the effects of OSA in cardiovascular disease patients for the diagnosis and management of OSA. In this article, we evaluate existing evidence relevant to this aspect in Singapore.
Prognosis of CVD Patients With OSA
There is an increasing focus on the implications of OSA in patients with coronary artery disease. In Singapore, it was observed that 65.7% of 120 patients presenting with acute myocardial infarction (AMI) had previously undiagnosed OSA (AHI > 15).8 The prevalence is consistent with clinical studies performed in the USA 9 and Portugal 10 that reported 66.4% and 43.1% of ACS patients had OSA (AHI > 10). However, a Japanese study reported a lower prevalence of 43% in a Japanese hospital when polysomnography was performed about two weeks after AMI onset.11
After 18 months follow up of the patient cohort, it was reported that severe OSA was an independent predictor of adverse events.12 Such patients with severe OSA have lower event-free survival rate and are 5.4 times more likely to suffer adverse events such as death, reinfarction, stroke, unplanned target vessel revascularization, and heart failure requiring hospitalization.
OSA is also associated with worse angiographic outcomes in patients with coronary artery disease. In a local study, the target vessel revascularization rate among patients with severe OSA was three times as high as those in the non-severe OSA group and that the late lumen loss of endothelial progenitor cell capturing stent was similar to that of bare metal stent.13
Advocating for More Effective OSA Screening
Earlier paragraphs have highlighted OSA as a growing health concern worldwide. However, some studies indicate that OSA remains highly underdiagnosed even in people with obesity or hypertension.14 According to a March 2011 ACC survey, 42% of cardiologists indicate a lack of satisfaction with the effectiveness of sleep apnea therapy as their primary barrier for referring patients to sleep centers and 29% believe the next barrier was the cost of a sleep study to the patient.
Perhaps one solution is to use a simple and validated screening tool such as the Berlin Questionnaire (BQ), Epworth Sleepiness Scale (ESS) and STOP-BANG questionnaire. The BQ contains 10 questions covering three categories including 1) snoring severity, 2) excessive daytime sleepiness, and 3) history of high blood pressure or obesity. The patient is instructed to answer questions to all three categories, and it is then scored by the physician or medical staff. The effectiveness of BQ is demonstrated by a number of studies which identified high risk OSA patients in different patient cohorts with prevalence ranging from 37.5% to 65%, including primary care setting, 15 acute coronary syndrome,16 recent myocardial infarction,17 cardiac rehabilitation,18 atrial fibrillation,19 and general cardiology service.7
Although screening questionnaires such as the BQ and ESS are relatively effective as OSA screening tools, the majority of these questions asked are non-specific symptoms which are highly present in CAD patients. As such, we set out to see if a clinical risk stratification tool (CHADS2 score) would have a role in clinical identification of OSA CAD patients.20 The CHADS2 score is a clinical prediction tool that characterizes the risk of thromboembolic stroke21 in patients with non-valvular atrial fibrillation, and is widely used to aid in long-term anticoagulation decisions. Patients are scored by adding up the points that correspond to factors of CHADS2. The factors include congestive heart failure, hypertension, age (at or above 75 years), diabetes mellitus and prior stroke. Each factor has been consistently reported to demonstrate an association with OSA in population-based epidemiological studies.22, 23 Using a different age cut-off of ≥65 years old because existing data shows a higher risk of OSA in people aged ≥65 24, the results showed that OSA patients had significantly higher CHA65DS2 scores than non-OSA patients (after adjusting for age, body mass index and clinical presentation). When compared to a patient with a CHA65DS2 score of 0, a patient with a CHA65DS2 score of one is 1.97 times more likely to have OSA. This risk increases to 2.85 times when CHA65DS2 score is at least two.
Singapore's Approach to OSA
Singapore is not spared from the insidious rising incidence of OSA. From an economic viewpoint, the majority of OSA patients comes from the economically-productive middle-aged segment of the local population. And from a medical viewpoint, OSA has several cardiovascular complications (e.g. arrhythmias, pulmonary hypertension, myocardial infarction, heart failure, systemic hypertension). We also highlighted the association of OSA is with a worse prognosis for patients who have co-morbid cardiovascular diseases.
One way to start is to address the under-diagnosis of OSA. Cardiologists in local practice can be encouraged to use screening questionnaires (such as the BQ or STOP-BANG) or a validated clinical prediction rule (CHA65DS2 score) to guide patient referrals for a sleep study. Such a focused approach would make more effective use of sleep studies. In the war against OSA, the goal is to achieve early diagnosis, start targeted treatment and improve long-term patient outcomes.
- Puvanendran K, Goh KL. From snoring to sleep apnea in a Singapore population. Sleep Res Online 1999;2:11-4.
- Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea – a population health perspective. Am J Respir Crit Care Med 2002;165:1217-39.
- Lim LL, Tham KW, Fook-Chong SMC. Obstructive Sleep Apnoea in Singapore: Polysomnography Data From a Tertiary Sleep Disorders Unit. Ann Acad Med Singapore 2008;37:629-36
- Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005;365:1046-53.
- Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study. Ann Intern Med 2012;156:115–22.
- Shahar E, Whitney CW, Redlne 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(1), 19-25.
- Loo G., et al, Screening of hospitalized patients at high risk of obstructive sleep apnea in general cardiology service, Int J Cardiol 2012, doi:10.1016/j.ijcard.2012.06.072
- Lee CH, Khoo SM, Tai BC et al. Obstructive sleep apnea in patients admitted for acute myocardial infarction. Prevalence, predictors, and effect on microvascular perfusion. Chest 2009;135(6), 1488-1495.
- Mehra R, Principe-Rodriguez K, Kirchner HL, Strohl KP. Sleep apnea in acute coronary syndrome: high prevalence but low impact on 6-month outcome. Sleep Med 2006;7(6), 521-528.
- Areias V, Romero J, Cunha K et al. Sleep apnea-hypopnea syndrome and acute coronary syndrome – an association not to forget. Rev. Port. Pneumol 2012; 18(1), 22-28.
- Nakashima H, Katayama T, Takagi C, et al. Obstructive sleep apnoea inhibits the recovery of left ventricular function in patients with acute myocardial infarction. Eur Heart J 2006; 27:2317–2322
- Lee CH, Khoo SM, Chan MY et al. Severe Obstructive Sleep Apnea and Outcomes Following Myocardial Infarction. Journal of Clinical Sleep Medicine 2011, Vol. 7, No. 6:616-621
- Low AF, Lee CH, Teo SG, et al. Effectiveness and safety of the Genous endothelial progenitor cell-capture stent in acute ST-elevation myocardial infarction. Am J Cardiol 2011;108:202-5.
- Fuhrman C, Fleury B, Nguyên XL, Delmas M-C, Symptoms of sleep apnea syndrome: High prevalence and underdiagnosis in the French population, Sleep Medicine, Volume 13, Issue 7, August 2012, Pages 852-858, ISSN 1389-9457.
- Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med 1999;131:485–91.
- Jesus EV, Dias-Filho EB, Mota Bde M, et al. Suspicion of obstructive sleep apnea by Berlin Questionnaire predicts events in patients with acute coronary syndrome. Arq Bras Cardiol 2010;95:313–20.
- Sert Kuniyoshi FH, Zellmer MR, Calvin AD, et al. Diagnostic accuracy of the Berlin Questionnaire in detecting sleep-disordered breathing in patients with a recent myocardial infarction. Chest 2011;140:1192–7.
- Sharma S, Parker AT. Prevalence of obstructive sleep apnea in a patient population undergoing cardiac rehabilitation. J Cardiopulm Rehabil Prev 2011;31:188–92.
- Chilukuri K, Dalal D, Marine JE, et al. Predictive value of obstructive sleep apnoea assessed by the Berlin Questionnaire for outcomes after the catheter ablation of atrial fibrillation. Europace 2009;11:896–901.
- Loo G, et al, Relationship between CHA65DS2 score and obstructive sleep apnea (CHA65DS2 and OSA), Int J Cardiol 2013, http://dx.doi.org/10.1016/j.ijcard.2013.07.221
- Gage BF, van Walraven C, Pearce L, et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 2004;110:2287–92.
- Somers VK, White DP, Amin R, 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. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 2008;118:1080–111.
- Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA 2004;291:2013–6.
- Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc 2008;5:136–43.
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