In Keynote Address, Dr Susan Redline Refutes Report Claiming CPAP May Not Improve Health Outcomes

During the SLEEP 2022 keynote address, Susan Redline, MD, MPH, broke down a controversial recent report from the Agency for Healthcare and Research Quality (AHRQ) claiming that there isn’t enough research to support the claim that continuous positive airway pressure (CPAP) improves health outcomes, especially in cardiovascular disease (CVD).

Redline, a professor of epidemiology at Harvard T.H. Chan School of Public Health and a physician in the Division of Pulmonary Medicine in the Department of Medicine at Beth Israel Deaconess Medical Center, refuted the findings of the report and shared other evidence that suggests that sleep apnea may be made up of multiple disorders.

The SLEEP 2022 annual meeting of the Associated Professional Sleep Societies is being held in Charlotte, North Carolina, from June 4 to June 8.

The AHRQ report was based on a series of literature reviews and focused primarily on 3 studies (SAVE, RICCADSA, and ISAACC), all of which had several limitations, Redline said. The studies often contained small sample sizes and excluded patients who would contribute to a resilient cohort, such as those who are excessively tired. They also required use of a CPAP machine for about 3 hours per night instead of the entire night, suggesting that the efficacy of CPAP was not fully assessed.

Furthermore, they relied on the apnea-hypopnea index (AHI), a risk prediction metric that predicts obstructive sleep apnea (OSA). The metric does not show associations with CVD, stroke, or mortality in women and only modest association with sleepiness and quality of life. It also does not identify sleep, disruption, autonomic stresses, or phenotypic heteroigeneity.

Redline noted that AHI measurements may also be restrictive in that she believes that sleep apnea may actually be a combination of multiple sleep disorders. This is because of the varying degree of symptoms faced by patients with a diagnosis of sleep apnea.

“There are many phases of sleep apnea. It occurs commonly in obese patients, but also in nonobese [patients]. It occurs commonly in the elderly, but also in children and during pregnancy. Some patients complain of disabling hypersomnia, but others complain of insomnia. And the clinical variability is further emphasized across the spectrum of sleep symptoms,” Redline explained.

Sleep apnea has a long list of risk factors as well, ranging from phenotypic characteristics to lifestyle exposures to genetic differences. Redline said that the detection of smoking history, genes related to cardiovascular health and hypoxia, and blood biomarkers could all help inform CVD risk prediction models. However, identifying the true CVD risk for patients with OSA may be hindered by multiple factors, some of which may be unknown to health care professionals.

“One of the big blind spots we have, when we study the relationship with CPAP and cardiovascular disease, is that we have no idea how long most of our patients have had sleep apnea before they've been treated,” noted Redline.

Women are known to experience the onset of sleep apnea later in life than men. Additionally, compared with men, women experience more hypopneas, fewer apneas, shorter apneas, more arousals, less hypoxia, more REM-dependent OSA, less positional dependency, less sleepiness, and more fatigue. Similar disparities have been observed among people of color with OSA.

Redline said that moving forward, clinical trials need to be larger, longer, and adaptive to enrich the sample based on hypoxic burden and heart rate phenotypes. Metrics that could identify individuals at risk for OSA-related CVD need to be improved to take into account all endotypes, physiological response markers, sex-specific considerations, and genetics. Metrics should also contain the potential for machine learning.

Despite the many issues that Redline raised about the AHRQ report, she said that it revealed what more the OSA and sleep research communities could do to improve detection for CVD risk.

“I'm not upset by this report. I don't agree with everything in the report, but I think there is a call to action in our field. I think we have the need, the opportunity, the tools, and the wherewithal to improve our case identification, use better metrics, incorporate mediums of disease in our thinking, and, with [the National Institutes of Health]’s help and maybe industry’s help, identify better studies,” she concluded.