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Review of Sleep Apnea and Cardiovascular Disease: AHA/ACCF Expert Consensus Document
The association between sleep apnea (SA) and cardiovascular disease (CVD) has been observed and studied for decades. Population and referral based studies have shown a common co-aggregation of SA [defined as obstructive sleep apnea (OSA) and/or central sleep apnea (CSA)] and CVD such as hypertension, heart failure, cardiac arrhythmias and stroke. Despite this recognition, fundamental questions remain about this relationship, such as whether there is a causal role in disease generation or propagation and whether treatment of SA can appreciably impact important CVD outcomes.
To address these and other clinical and research issues, a panel of experts convened jointly by the American Heart Association and the American College of Cardiology Foundation published a landmark scientific statement, Sleep Apnea and Cardiovascular Disease, chaired by Dr. Virend Somers and co-chaired by Drs. David White and Raouf Amin.1
The document offers a comprehensive overview of both OSA and CSA, including definitions, basic pathophysiologic mechanisms, diagnostic criteria and treatment options. It is important to note that nearly all of the literature regarding SA treatment focuses on positive airway pressure (PAP) devices. Other interventions such as weight loss, while likely to impact both SA and CVD, are scantily studied. There is also a review of epidemiology, particularly in the context of clinical presentation. That is, since CVD and SA are highly prevalent and so commonly co-exist, the clinician is likely to encounter the patient who has both.
The paper outlines pathophysiologic mechanisms in SA that may be operative in the genesis of CVD and that are probably important in patients with established CVD:
- Repetitive hypoxemia and reoxygenation (oxidative stress)
- Sympathetic Activation
- Repeated arousals from sleep
- Reduced heart rate variability
- Elaboration of vasoactive substances
- Heightened inflammation
- Endothelial dysfunction
- Hypercoagulability
- Intrathoracic pressure swings (OSA only)
Several pages are devoted to specific cardiovascular disorders and their relationship with sleep apnea. In this regard, there has been far more research published in the setting of OSA than in CSA.
Hypertension and OSA
Both disorders are commonly co-existent, suggesting a potential causative relationship. Although not definitively proven, the evidence led the Joint National Committee on the Detection and Management of Hypertension to cite OSA as an important identifiable cause of hypertension.
There have been multiple PAP treatment studies, including randomized controlled trials, which have shown generally positive but inconsistent effects of OSA treatment on blood pressure. In summary, the panel concluded that there are "moderate and variable effects" of PAP on BP in patients with OSA. The panel also highlighted two studies showing that oral appliances might also reduce BP in OSA.
Heart Failure and OSA
This paper highlights the lack of non-referral based epidemiological studies in heart failure and OSA. That said, available evidence suggests a high proportion of OSA in those with HF. Interestingly, the relationship may be bi-directional, where volume overload in HF leads to upper airway edema, thereby promoting collapse during sleep.
Hypertension may be an important intermediary mechanism linking OSA and HF, along with heightened adrenergic tone. However, it remains unknown whether or not OSA can actually cause HF or accelerates mortality in this population. Furthermore, while a few small studies of PAP usage show promising results on surrogate outcomes in HF, large treatment trials measuring harder endpoints, such as mortality, are sorely lacking.
Stroke and OSA
Again, there is substantial referral bias in the literature describing the relationship between OSA and stroke. Furthermore, the fact that sleep apnea (OSA and/or CSA) may be clinically recognized only after a stroke leads one to postulate that sleep apnea might occur as a result of the stroke. Accepting that assumption, it is important to recognize that there are multiple mechanisms by which pre-existing OSA might contribute to cerebrovascular disease, as outlined in the table above. However, current literature suggests only moderate effects of SA on stroke risk and rigorous treatment trials are generally lacking. One important area of interest is the effect of OSA on stroke recovery and rehabilitation.
Arrhythmias and OSA
OSA provides the milieu to study the classic cardiac response to hypoxemia, which is bradycardia. Additionally, other arrhythmias, particularly atrial fibrillation (AF) are reported frequently in observational studies of OSA. In fact, there is high biologic plausibility supporting a relationship. To date, however, the literature outlining effects of PAP treatment on arrhythmias in OSA remains immature, prompting the panel to remark that there are no conclusive studies of the effects of OSA treatment on arrhythmia outcomes. Notably, the panel also took up the issue of the use of atrial overdrive pacing and determined that there is no definitive evidence to support its use as a treatment for OSA.
The manuscript describes other important CVD, such as myocardial ischemia, pulmonary hypertension and renal disease, in the context of OSA, concluding that further study is needed to establish a causal relationship and to determine the role of OSA treatment in these disease states.
Central Sleep Apnea
The panel provides a nice overview of CSA, which is generally seen in the setting of heart failure (HF). At this point, it is unclear whether CSA (more specifically, Cheyne-stokes breathing pattern) is an epiphenomenon of HF or whether CSA in and of itself is a risk factor for worsening cardiac function in HF patients. In any event, it is generally felt that optimization of cardiac function is a prudent first step in improving CSA in the patient with HF. It is important to note that, despite these gaps in our understanding, the treatment of CSA is rapidly evolving, with more sophisticated PAP machines finding their way into the clinician's armamentarium. Thus, there is an urgent need to study the impact of CSA treatment with such devices on HF outcomes.
OSA in Children
An exploding area of interest is the increasing prevalence of obesity and OSA in the pediatric population and its burgeoning public health impact. The panel provides an excellent overview of a maturing literature, and reviews mechanisms of disease and the effects of treatments such as tonsillectomy and PAP therapy on important outcomes, while we await more definitive trials.
Future Directions from the Perspective of the National Center on Sleep Disorders Research/NHLBI
The panel provides guidance for pressing gaps in knowledge and of future research projects. Bullet points include:
- An urgent call for adequately powered clinical trials, particularly in high-risk populations
- The need to ascertain normative data in pediatric populations
- Incorporation of new and improved SA therapies in clinical trials
- Utilization of less expensive and more widely available diagnostic modalities in clinical trials
- Multidisciplinary cooperation in clinical trials
References
- 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. J Am Coll Cardiol 2008;52:686-717.
Keywords: Arrhythmias, Cardiac, Heart Failure, Hypertension, Referral and Consultation, Sleep Apnea Syndromes, Sleep Apnea, Central, Sleep Apnea, Obstructive, Stroke
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