Affiliations: Edmonton, AB, Canada
Dr. Sin is Assistant Professor of Medicine, University of Alberta.
Correspondence to: Don D. Sin, MD, FCCP, 2E4.29 Walter C. Mackenzie Centre, University of Alberta, Edmonton, AB, Canada T6G 2B7; e-mail: email@example.com
Increasingly, sleep-disordered breathing (SDB) is recognized as an important risk factor for coronary atherosclerosis and heart disease. Several large epidemiologic studies1–2
have demonstrated that SDB increases the risk of heart disease by approximately twofold to fourfold, independent of other risk factors. While the exact mechanisms responsible for this association are largely unknown, there is credible evidence to indicate SDB can increase systemic BP3–4
and sympathetic drive.5–
It may also elevate circulating levels of fibrinogen6–
and C-reactive protein,7–
triggering a cascade of events that eventually leads to thrombus formation in the coronary vasculature. Treatment of SDB, usually with continuous positive airway pressure, leads to significant improvements in these physiologic parameters.8
Despite these data, there are still major gaps in knowledge. In this issue of CHEST (see page 936), Hayashi and coworkers present intriguing new information that provides additional support for the role of SDB in the pathogenesis of atherosclerosis. They performed nocturnal pulse oximetry on 59 consecutive patients with coronary artery disease who were admitted to the hospital for coronary angiography. They found that patients with an elevated nocturnal oxygen desaturation index (ODI) had a higher clot burden than those with a normal ODI. More importantly, they observed this relationship to be “dose dependent,” such that those with the highest ODI had the largest clot burden while those with the lowest ODI had the lowest clot burden. Traditional risk factors such as hyperlipidemia and hypertension contributed very little to the model, after adjustments for ODI. Indeed, in their analysis, ODI by itself explained 13% of the variations in the Gensini score (p = 0.005), suggesting that events leading to nocturnal oxyhemoglobin desaturation are powerfully related to atherosclerosis. This carefully conducted epidemiologic study, therefore, suggests a “biological” gradient between (severity of) SDB and atherosclerotic burden among individuals with heart disease. This work adds to a growing body of literature supporting a causal link between SDB and ischemic heart disease.
The work by Hayashi and coworkers, however, raises some important questions; they used ODI to detect SDB, which assumed that apneas and hypopneas during sleep were responsible for the dips in oxyhemoglobin saturation in their cohort. However, the concordance between ODI and apnea-hypopnea indexes (AHIs) is far from perfect. In one report,9–
ODI had a sensitivity of only 51% and a specificity of 90% in identifying patients with SDB (defined by an AHI of ≥ 15 on polysomnography). In another study,10–
the sensitivity was < 50%, and the correlation coefficient between AHI and ODI was only 0.58, indicating only a modest association. In other studies,11–13
ODIs have been demonstrated to have moderate-to-high sensitivity but poor specificity in identifying patients with sleep apnea. False-positive findings were especially prominent among individuals with airflow obstruction.13
Given the suboptimal concordance between ODI and AHI, there is some uncertainty as to whether the patients with elevated ODI in the study by Hayashi and coworkers had obstructive sleep apnea. This doubt is further fueled by the observation that most of these patients were elderly and had normal or near-normal body mass indexes. Although individuals with normal body weight can acquire obstructive sleep apnea, it would be extremely unusual (and, indeed, unlikely) that obstructive sleep apnea would be found in > 70% of nonobese patients, as reported by Hayashi and coworkers.
Could some of the patients with elevated ODI in the study by Hayashi and coworkers have had central sleep apnea or Cheyne-Stokes respiration (CSA-CSR)? CSA-CSR has been reported to be common in patients with ischemic heart disease but, in most cases, such patients have evidence of left ventricular systolic dysfunction.14
In the study by Hayashi and coworkers, the patients had well-preserved left ventricular systolic function. Moreover, they only had a modest elevation in brain natriuretic peptide levels, making it unlikely that these patients had CSA-CSR.
In the study by Hayashi and coworkers, over half of the patients were current or former smokers. The average cigarette exposure time per patient was 23 to 27 pack-years, raising the possibility that some patients may have had impairments in lung function from obstructive airways disease. Although patients had normal daytime oxyhemoglobin saturation, this by no means precludes the possibility of subclinical obstructive airways disease. Patients with reduced lung function may have normal oxyhemoglobin saturations during wakefulness, but nocturnally they may experience significant dips in their oxyhemoglobin saturation even in the absence of discernible upper airway obstruction.15–
Importantly, there are strong epidemiologic data to indicate that reduced lung function increases the risk of coronary atherosclerosis and heart disease by twofold to threefold.16
Notwithstanding these concerns, the work of Hayashi and coworkers represents a major step forward in our understanding of the relationship between respiratory events during sleep and atherosclerosis. A severity-dependent association between ODI and clot burden provides further evidence of a causal link between SDB and ischemic heart disease; however, future work is needed to better define the factors responsible for nocturnal oxyhemoglobin desaturations in ischemic heart disease. In this sense, polysomnographic and spirometric data would be very helpful in further strengthening the notion that SDB is, indeed, a “heart-changing” experience.
Dr. Sin is supported by a New Investigator Award from the Canadian Institutes of Health Research and a Population Health Investigator Award from the Alberta Heritage Foundation for Medical Research.
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