Sleep-Disordered Breathing and Cardiovascular Disease
In recent years, there has been increasing awareness of the high prevalence and clinical significance of sleep-disordered breathing (SDB) and its effects on a range of cardiovascular conditions, including hypertension, heart failure (HF), myocardial infarction (MI), atrial fibrillation (AF), and type 2 diabetes.
SDB describes a group of disorders characterized by abnormalities in the frequency and/or depth of breathing while asleep. These intermittent episodes cause partial or complete obstruction of the upper airway, disrupting normal ventilation and sleep architecture. It not only causes poor sleep quality and daytime sleepiness, but has clinical consequences too.
Obstructive sleep apnea (OSA) is the most extreme variant, but other forms of SDB are highly prevalent, too. An analysis of 154 original investigations and reviews of sleep-related breathing disorders estimated that one in five adults has at least mild OSA and one in 15 adults has at least moderate OSA. Central sleep apnea is the most common SDB in patients with HF, occurring in an estimated 40-63% of HF patients. However, it may be more difficult to identify individuals with central sleep apnea since it does not tend to be associated with the typical excessive daytime sleepiness of OSA.
Case-control and retrospective studies first suggested that SDB is associated with an increased prevalence of coronary heart disease (CHD) and CHD-related outcomes, and large-scale cohort studies subsequently confirmed these findings. In the Sleep Heart Health Study (SHHS), for example, several cardiovascular disease outcomes, including MI and stroke, were associated with SDB. Also, the Nurses Health Study prospectively observed that self-reported snoring, a cardinal symptom of SDB, may be an independent risk factor for the development of CHD.
There are several physiologic disturbances that can lead to cardiovascular consequences (Figure 1). As for specific cardiovascular effects, OSA places a strain on cardiac output by virtue of hypoxemia, large negative intrathoracic pressures, and high swings in systemic blood pressure. Here are other ways that SDB clinically affects specific heart conditions:
(Enlarge Image)
Figure 1.
Heart Failure. As noted, central sleep apnea is highly prevalent in patients with left ventricular (LV) dysfunction and it often occurs before the development of overt HF. The main clinical significance of central sleep apnea is its association with increased mortality independent of other known risk factors. Also, OSA has the potential to worsen ventricular dysfunction in patients with overt HF.
Myocardial Infarction. Recently, investigators analyzed 1,660 patients with a first acute MI and found a strong association in the first 28 days after infarction between snoring and mortality. Occasional and regular heavy snorers had a 2.04 (95% confidence interval [CI], 1.50 to 2.79) and 3.30 (95% CI, 2.37 to 4.58) hazard ratio for mortality respectively within the first 28 days after controlling for age, gender, obesity, history of diabetes and hypertension, physical activity, smoking, and education.
Atrial Fibrillation. In a cohort of 3,542 people who underwent complete polysomnography, obesity and OSA were independent risk factors for incident AF over an average of about 5 years of follow-up (Figure 2). Both obesity and OSA may contribute to the looming epidemic of AF and both conditions should be recognized as independent risk factors for incident AF.
(Enlarge Image)
Figure 2.
In another recent study, investigators prospectively evaluated SDB in a relatively young patient population (mean age 55 years) with paroxysmal or persistent AF and normal LV function. The control population was comprised of patients referred to the same tertiary arrhythmia center during the same 18-month period but without AF. Among the AF group, there was a high prevalence of SDB (Figure 3) and more patients with significant SDB than the controls. After adjusting for relevant covariates, the odds ratio for the association between AF and SDB was 3.04 (95% CI 1.24-7.46, p = 0.02). In general, the authors said, OSA should be considered in patients with arrhythmias (including bradyarrhythmias) and — like the large cohort study above — particularly those individuals who are obese or hypertensive, regardless of the presence or absence of LV dysfunction.
(Enlarge Image)
Figure 3.
Type 2 Diabetes. SDB is associated with insulin resistance and glucose intolerance, plus it is frequently found in individuals with type 2 diabetes. In a paper published in July 2008, the International Diabetes Federation Task Force on Epidemiology and Prevention "strongly recommends" that health professionals working in both type 2 diabetes and SDB adopt clinical practices to ensure that a patient presenting with one condition is considered for the other.
Is Intervention Effective? The adverse effects of OSA on LV function can be at least partially reversed with continuous positive airway pressure (CPAP). In a 2007 issue of the Journal of the American College of Cardiology, Wang et al. reported a single-center prospective observational study comparing the mortality of patients with coexistent HF and OSA with that of patients with only HF. Nearly 25% of the patients had OSA and risk of death was nearly three times higher in those with OSA versus those with mild or no OSA (Figure 4). None of the patients with HF and treated OSA died during 39-month follow-up. An accompanying editorial noted that "early diagnosis of OSA and initiation of effective CPAP therapy are of paramount importance in patients with coexistent HF and OSA."
(Enlarge Image)
Figure 4.
Evidence also suggests that CPAP decreases health care costs in moderate-to-severe OSA and is associated with lower recurrence of AF. Importantly, in patients with OSA, CPAP reduces the risk of car accidents from an excess risk of two to seven times greater than the background population to a level comparable to the general population.
It should be noted that current data do not support routine use of CPAP in chronic stable congestive cardiac failure unless there is co-existent OSA. Bi-level pressure support using newer devices that may more effectively treat both OSA and central sleep apnea are being evaluated.
Recently, investigators reported that 6 months of aerobic exercise training increased exercise capacity and improved central sleep apnea in patients with chronic HF from systolic dysfunction. Whether reducing central sleep apnea in this manner reduces the independent risk for poor long-term prognosis associated with SDB in this setting is unknown.
Investigators also have compared blood pressure response to nasal CPAP in a group of middle-aged men with mild-to-moderate untreated hypertension. Nearly half of the study group had SDB and 3 weeks of nasal CPAP treatment caused a substantial lowering of nocturnal systolic (-7.8 mm Hg, p = 0.02 versus no SDB) and diastolic (-5.3 mm Hg, p = 0.03 versus no SDB) blood pressure values. The authors noted that a reduction in blood pressure similar to that obtained with CPAP has been associated with a substantial reduction in the incidence of cerebrovascular accidents and MI in previous studies.
Finally, in late 2007, investigators published a retrospective cohort study of patients with OSA who subsequently underwent percutaneous coronary intervention (PCI). Patients were stratified according to whether they were treated for OSA (n = 175) or not (n = 196). Patients treated for OSA had a statistically significant decreased number of cardiac deaths on follow-up compared to untreated OSA patients (3% [95% CI 0% to 6%] vs. 10% [95% CI 5% to 14%] after 5 years, p = 0.027) (Figure 5), as well as a trend toward decreased all-cause mortality (p = 0.058). The authors concluded that screening for and treating OSA in patients with CHD who may undergo PCI may result in decreased cardiac death.
(Enlarge Image)
Figure 5.
In this interview, Dr. Bernard J. Gersh, who participated in several of the studies summarized here, discusses the cardiovascular mechanisms of sleep-disordered breathing and the diagnosis and management of this large population of patients.
Abstract and Cardiovascular Effects
Abstract
In recent years, there has been increasing awareness of the high prevalence and clinical significance of sleep-disordered breathing (SDB) and its effects on a range of cardiovascular conditions, including hypertension, heart failure (HF), myocardial infarction (MI), atrial fibrillation (AF), and type 2 diabetes.
SDB describes a group of disorders characterized by abnormalities in the frequency and/or depth of breathing while asleep. These intermittent episodes cause partial or complete obstruction of the upper airway, disrupting normal ventilation and sleep architecture. It not only causes poor sleep quality and daytime sleepiness, but has clinical consequences too.
Obstructive sleep apnea (OSA) is the most extreme variant, but other forms of SDB are highly prevalent, too. An analysis of 154 original investigations and reviews of sleep-related breathing disorders estimated that one in five adults has at least mild OSA and one in 15 adults has at least moderate OSA. Central sleep apnea is the most common SDB in patients with HF, occurring in an estimated 40-63% of HF patients. However, it may be more difficult to identify individuals with central sleep apnea since it does not tend to be associated with the typical excessive daytime sleepiness of OSA.
Case-control and retrospective studies first suggested that SDB is associated with an increased prevalence of coronary heart disease (CHD) and CHD-related outcomes, and large-scale cohort studies subsequently confirmed these findings. In the Sleep Heart Health Study (SHHS), for example, several cardiovascular disease outcomes, including MI and stroke, were associated with SDB. Also, the Nurses Health Study prospectively observed that self-reported snoring, a cardinal symptom of SDB, may be an independent risk factor for the development of CHD.
Cardiovascular Effects
There are several physiologic disturbances that can lead to cardiovascular consequences (Figure 1). As for specific cardiovascular effects, OSA places a strain on cardiac output by virtue of hypoxemia, large negative intrathoracic pressures, and high swings in systemic blood pressure. Here are other ways that SDB clinically affects specific heart conditions:
(Enlarge Image)
Figure 1.
Heart Failure. As noted, central sleep apnea is highly prevalent in patients with left ventricular (LV) dysfunction and it often occurs before the development of overt HF. The main clinical significance of central sleep apnea is its association with increased mortality independent of other known risk factors. Also, OSA has the potential to worsen ventricular dysfunction in patients with overt HF.
Myocardial Infarction. Recently, investigators analyzed 1,660 patients with a first acute MI and found a strong association in the first 28 days after infarction between snoring and mortality. Occasional and regular heavy snorers had a 2.04 (95% confidence interval [CI], 1.50 to 2.79) and 3.30 (95% CI, 2.37 to 4.58) hazard ratio for mortality respectively within the first 28 days after controlling for age, gender, obesity, history of diabetes and hypertension, physical activity, smoking, and education.
Atrial Fibrillation. In a cohort of 3,542 people who underwent complete polysomnography, obesity and OSA were independent risk factors for incident AF over an average of about 5 years of follow-up (Figure 2). Both obesity and OSA may contribute to the looming epidemic of AF and both conditions should be recognized as independent risk factors for incident AF.
(Enlarge Image)
Figure 2.
In another recent study, investigators prospectively evaluated SDB in a relatively young patient population (mean age 55 years) with paroxysmal or persistent AF and normal LV function. The control population was comprised of patients referred to the same tertiary arrhythmia center during the same 18-month period but without AF. Among the AF group, there was a high prevalence of SDB (Figure 3) and more patients with significant SDB than the controls. After adjusting for relevant covariates, the odds ratio for the association between AF and SDB was 3.04 (95% CI 1.24-7.46, p = 0.02). In general, the authors said, OSA should be considered in patients with arrhythmias (including bradyarrhythmias) and — like the large cohort study above — particularly those individuals who are obese or hypertensive, regardless of the presence or absence of LV dysfunction.
(Enlarge Image)
Figure 3.
Type 2 Diabetes. SDB is associated with insulin resistance and glucose intolerance, plus it is frequently found in individuals with type 2 diabetes. In a paper published in July 2008, the International Diabetes Federation Task Force on Epidemiology and Prevention "strongly recommends" that health professionals working in both type 2 diabetes and SDB adopt clinical practices to ensure that a patient presenting with one condition is considered for the other.
Is Intervention Effective? The adverse effects of OSA on LV function can be at least partially reversed with continuous positive airway pressure (CPAP). In a 2007 issue of the Journal of the American College of Cardiology, Wang et al. reported a single-center prospective observational study comparing the mortality of patients with coexistent HF and OSA with that of patients with only HF. Nearly 25% of the patients had OSA and risk of death was nearly three times higher in those with OSA versus those with mild or no OSA (Figure 4). None of the patients with HF and treated OSA died during 39-month follow-up. An accompanying editorial noted that "early diagnosis of OSA and initiation of effective CPAP therapy are of paramount importance in patients with coexistent HF and OSA."
(Enlarge Image)
Figure 4.
Evidence also suggests that CPAP decreases health care costs in moderate-to-severe OSA and is associated with lower recurrence of AF. Importantly, in patients with OSA, CPAP reduces the risk of car accidents from an excess risk of two to seven times greater than the background population to a level comparable to the general population.
It should be noted that current data do not support routine use of CPAP in chronic stable congestive cardiac failure unless there is co-existent OSA. Bi-level pressure support using newer devices that may more effectively treat both OSA and central sleep apnea are being evaluated.
Recently, investigators reported that 6 months of aerobic exercise training increased exercise capacity and improved central sleep apnea in patients with chronic HF from systolic dysfunction. Whether reducing central sleep apnea in this manner reduces the independent risk for poor long-term prognosis associated with SDB in this setting is unknown.
Investigators also have compared blood pressure response to nasal CPAP in a group of middle-aged men with mild-to-moderate untreated hypertension. Nearly half of the study group had SDB and 3 weeks of nasal CPAP treatment caused a substantial lowering of nocturnal systolic (-7.8 mm Hg, p = 0.02 versus no SDB) and diastolic (-5.3 mm Hg, p = 0.03 versus no SDB) blood pressure values. The authors noted that a reduction in blood pressure similar to that obtained with CPAP has been associated with a substantial reduction in the incidence of cerebrovascular accidents and MI in previous studies.
Finally, in late 2007, investigators published a retrospective cohort study of patients with OSA who subsequently underwent percutaneous coronary intervention (PCI). Patients were stratified according to whether they were treated for OSA (n = 175) or not (n = 196). Patients treated for OSA had a statistically significant decreased number of cardiac deaths on follow-up compared to untreated OSA patients (3% [95% CI 0% to 6%] vs. 10% [95% CI 5% to 14%] after 5 years, p = 0.027) (Figure 5), as well as a trend toward decreased all-cause mortality (p = 0.058). The authors concluded that screening for and treating OSA in patients with CHD who may undergo PCI may result in decreased cardiac death.
(Enlarge Image)
Figure 5.
In this interview, Dr. Bernard J. Gersh, who participated in several of the studies summarized here, discusses the cardiovascular mechanisms of sleep-disordered breathing and the diagnosis and management of this large population of patients.