High pressure from CPAP therapy may increase harm: Can low-pressure PAP therapy be effective without compromising AHI?

The Association Between High CPAP Pressures and Cardiovascular Risks

The ‘gold-standard’ for Obstructive Sleep Apnea (OSA) treatment, Continuous Positive Airway Pressure (CPAP), has long been assumed to decrease the risk of cardiovascular disease (CVD) in patients who adhere to treatment. This association has been made due to the ability of CPAP to reduce intermittent hypoxia and improve sleep quality, ^1, 2both factors in the development of CVD.^[1]  Despite longitudinal and observational studies demonstrating a relationship between CPAP adherence and decreased CVD risk,^{3, 4} this association has not been proven in randomized clinical trials, bringing into question the actual impact of CPAP therapy on CVD risk. 

Recent studies conducted by Sanja Jelic, MD, Yuksel Peker, MD and team, investigated this question.^{1, 5} The studies hypothesized that CPAP therapy may have unrecognized and potentially harmful effects that counteract its known beneficial effects (e.g. elimination of hypoxia). The studies found that patients undergoing CPAP treatment actually had increases in the endothelial proinflammatory marker angiopoietin-2.^{1, 5} Despite treating the OSA and reducing hypoxic events, the high therapeutic air pressure associated with CPAP treatment may be outweighing the perceived benefits of therapy by causing additional inflammation and increased CVD risk.⁵

OSA, CPAP, and Inflammation

Untreated Obstructive Sleep Apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD).^6,7OSA is thought to lead to an increased risk of CVD due to inflammation caused by the recurrent dips in oxygen throughout the night.⁸ Since CPAP machines eliminate intermittent hypoxia by delivering pressurized air and maintaining an open airway, it was believed that CPAP would also reduce the risk of CVD.  

However, the studies conducted by Jelic, Peker and team demonstrate that patients using CPAP machines at higher pressures, a therapy mode for treating moderate to severe cases of OSA, actually led to elevated levels of angiopoietin-2.  Angiopoietin-2 is associated with a greater risk of CVD.^{9, 10} Since angiopoietin-2 levels are often elevated in other patient populations, it is critical to expand research of CPAP treatment to include OSA patients where cardiovascular risk is already a concern due to pre-existing inflammation. This could include people suffering from both OSA and other inflammatory conditions such as cancer, COPD, ⁵ diabetes,⁹ etc.

Therapeutic pressure settings on CPAP devices increase depending on the severity of OSA – mild cases use lower pressures while moderate and severe cases use higher pressures. It is estimated that approximately 425M people worldwide suffer from moderate to severe OSA¹¹ which calls for CPAP treatment with medium to high therapeutic pressures. Given results from Jelic, Peker and team, this patient population could benefit significantly from lower therapeutic pressures that effectively treat their OSA without increasing their CVD risk via pro-inflammatory effects. 

Broader Implications- Adjusting the Approach to CPAP Therapy

The balance between effectively treating OSA and managing the impact of high-pressure CPAP therapy, including CVD risks, is complex and challenging. Healthcare providers should not only seek to improve OSA but should also maintain the broader goal of decreasing CVD risk in these patients.

The results from the Jelic, Peker and team studies call for significant improvements in the optimization of CPAP therapy.  However, reducing Apnea-Hypopnea Index (AHI) to <5 has proven to reduce risks of other comorbidities,¹²suggesting that lowering the overall pressures to reduce inflammatory effects would compromise the reduction in AHI. Innovation is needed to ensure that CPAP therapy protects cardiovascular health and limits inflammatory effects, while still reducing hypoxic events throughout the night in patients with moderate and severe OSA.

Can we lower treatment pressure and avoid an increase in AHI, in moderate and severe OSA?

NovaResp’s cMAP™ technology has been developed to provide personalized, more comfortable CPAP therapy to patients suffering from mild to severe OSA. cMAP™ is a clinically validated and patented algorithm that uses AI to predict apneaic events before they happen. Early prediction of these events permits the use of lower air pressures, which leads to greater patient comfort. Given the recent results from Peker and Selic, this further suggests that cMAP™ could reduce the inflammatory effects observed in patients being treated with high pressure therapy without sacrificing the necessary reduction in AHI. cMAP™ is an important step in CPAP innovation, and could lead to a treatment where AHI reduction is maintained (<5) using low pressures that do not trigger angiopoietin-2 production. This is a ground-breaking step in treating OSA to reduce CVD, particularly in those patients already suffering from inflammatory conditions and at higher risk of CVD. 

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