Cardiovascular disease (CVD) is a main cause of morbidity and disease all over the world. Its high prevalence creates a demand for improvement of both therapy methods and risk identification and management. Obstructive sleep apnea (OSA) is highly prevalent in CVD patients (40-60%). It has been shown to increase risk and worsen outcomes of various forms of CVD including hypertension, stroke, heart failure (HF), coronary artery disease, and atrial fibrillation (AF). A recently published review paper by the American Heart Association (AHA) scanned current literature on the association between OSA and CVD, with a special emphasis on suggesting clinical management strategy.
Of all CVD associated with OSA, the relationship with hypertension is the best established and was demonstrated in numerous studies. One influential study on 709 patients found a linear ,dose-dependent relationship between the severity of OSA at baseline and the relative risk of developing hypertension during follow-up. The effect of OSA is particularly strong when the hypertension is persistent(i.e., requires more than three antihypertensive agents for controlling blood pressure), reflecting in up to two times higher OSA prevalencein those patients(compared to essential hypertensive patients).Continuous positive airway pressure CPAP) treatment has proven to be beneficial for hypertension. ln a recent meta-analysis of five randomized trials enrolling 457 total patients, a significant reduction was found in 24-hour ambulatory blood pressure as well as a mean nocturnal diastolic blood pressure in patients treated with CPAP.
A strong association was also found between OSA and pulmonary hypertension (PH): 10% to 20% of patients with moderate-to-severe OSA have coexisting PH, and the prevalence of OSA in patients with PH diagnosed by right heart catheterization has been estimated to be 70% to 80%. OSA was shown to play a causative part in PH pathophysiology through both direct and indirect pathways. It increases right-sided preload, leads to right ventricular remodeling and dysfunction, and contributes to left HF with associated post-capillary PH. Importantly, the presence of OSA in patients found to have severe PH has been associated with increased mortality. Current literature suggests a beneficial outcome for OSA treatment on PH. In the one randomized trial to date, treatment of OSA with CPAP was associated with a significant reduction in pulmonary artery systolic pressure when compared with a sham device.
Sleep apnea (especially central) is highly prevalent in HF patients (50 to 70%) and has been associated with increased risk of adverse outcomes and mortality. Several pathophysiologic processes that result directly from apneic events may explain this association, including activation of the sympathetic nervous system as well as increased preload and afterload resulting from perturbation of intrathoracic pressure while attempting to inspire against occluded airways. Whether PAP therapy has a beneficial role for HF patients is still unclear. Early studies found advantages for sleep apnea therapy, including reduction of sympathetic activity and improved left ventricular systolic and diastolic function. However more recent studies are less conclusive; while one study found a reduction in mortality following treatment with CPAP, another found an increase in cardiovascular mortality following treatment with Adaptive Servoventilation (ASV). Postulated mechanisms for worsening outcomes include reductions in cardiac output related to the higher levels of PAP delivered in ASV mode, as well as the hypothesis that CSA is actually a compensatory mechanism in patients with severe HF with beneficial properties that were attenuated by ASV treatment. The current recommendation is that ASV mode should not be used in patients with HF and low ejection fraction, in whom there is evidence of harm.
The association between OSA and AF persists after controlling for confounding conditions such as systemic hypertension, obesity, and HF, and results in up to 39% OSA prevalence in AF patients. The main mechanisms underlying this association are nocturnal surges in sympathetic tone, systemic hypertension, and structural remodeling, particularly of the atria. CPAP therapy has been found to be beneficial for AF burden and risk of recurrence. In one study of >10,000 patients with AF, those with coexisting OSA had significantly worse AF symptoms and outcomes. CPAP treatment for those patients significantly decreased the chances to progress to permanent AF. Furthermore, multiple observational studies have demonstrated a significant reduction in the risk of recurrent AF following catheter ablation among OSA patients treated with CPAP as compared with OSA patients not receiving treatment.
Beyond AF, OSA has been linked with a spectrum of other cardiac rhythm disturbances, such as bradycardia (22% of moderate-to-severe OSA prevalence) and tachycardia (4.5 times higher prevalence of severe OSA compared with controls). Importantly, an increased risk of sudden cardiac death has been reported in patients with severe OSA, particularly among those observed to have nocturnal oxygen desaturation to <78%. Some studies suggest a beneficial role for CPAP treatment in reducing rhythm disturbances, but small sample sizes and the predominantly observational nature of these trials demand further investigation.
Coronary Artery Disease and Cerebrovascular Disease
Associations with OSA have also been identified between coronary artery disease (CAD) and cerebrovascular disease. The main pathophysiologic mechanisms linking OSA to these CVDs are increased sympathetic nervous system activity, oxidative stress, and predilection to poorly controlled and/or resistant hypertension. Treatment of OSA with CPAP has been shown to mitigate these processes, offering a plausible mechanism by which treating OSA could influence cardiovascular outcomes. Moreover, various studies demonstrated a significant reduction in mortality following OSA treatment. However, randomized trials have failed to establish the benefit of OSA treatment in those conditions. In the largest randomized controlled trial, 2717 moderate-to-severe OSA patients with either CAD or cerebrovascular disease, were randomized to CPAP plus usual care or usual care alone and were followed for a mean period of 3.7 years. The trial failed to demonstrate a significant reduction in the primary endpoint (e.g., cardiovascular death and stroke) following CPAP treatment, however, some secondary endpoints (e.g., snoring and daytime sleepiness) did show some improvement.
Other links between OSA and CVD
Several randomized trials examined whether PAP therapy affects the risk of developing a CVD. The results did not support the treatment’s efficacy in reducing the risk of adverse cardiovascular events, although due to some limitations of these studies the topic requires further investigation. OSA increases the risk of respiratory complications during CVD-related surgery and may lead to postoperative AF and other cardiac complications. This has prompted many centers to incorporate screening for OSA as a routine component of preoperative assessment.
- Evaluation: Given the high prevalence of sleep apnea in patients with known CVD, the AHA reviewers recommend that clinicians perform routine screening for symptoms of SDB in patients with established CVD. Moreover, for some CVDs (resistant hypertension, pulmonary hypertension, and recurrent AF) the recommendation is that patients should undergo a comprehensive sleep assessment even in the absence of SDB symptoms. Routine screening for nocturnal symptoms of SDB should be repeated at defined intervals during long-term follow-up in CVD patients.
- Treatment: All CVD patients with diagnosed OSA should be offered treatment according to their condition—CPAP, oral appliances, upper airways surgery, and weight loss.
- Diagnosis: In agreement with the recommendations from the 2017 American Academy of Sleep Medicine regarding diagnosing OSA, the reviewers suggest that the diagnostic testing strategy should not rely on questionnaires and other prediction tools alone but should always involve sleep evaluation. Some complicated cases may require in-lab polysomnography, but for most, an accurate home sleep apnea testing (HSAT) may be the better diagnostic tool.
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Jeremy R. Tietjens el at. Obstructive Sleep Apnea in Cardiovascular Disease: A Review of the Literature and Proposed Multidisciplinary Clinical Management Strategy, Journal of the American Heart Association. 2019;8