CPAP May Cut Cardiac Events in Some At-Risk Apnea Patients

Continuous positive airway pressure (CPAP) therapy seemed to reduce heart attack and stroke risk among certain patients with heart disease and obstructive sleep apnea (OSA), even in those without symptoms of daytime sleepiness, a researcher reported.

Among non-sleepy OSA patients whose pulse rates rose significantly during apnea and hypopnea events, CPAP treatment appeared to protect against cardiac events, suggesting that elevated heart rate in response to respiratory events is a novel risk factor that could help identify at-risk patients, according to Ali Azarbarzin, PhD, of Brigham and Women's Hospital in Boston.

In addition, CPAP may improve cardiovascular (CV) outcomes in certain OSA patients without symptoms related to sleepiness, despite recent suggestions by federal health officials that this might not be the case, he noted in a presentation at the American Thoracic Society virtual meeting.

In a recent draft document, the Agency for Health Research and Quality (AHRQ) concluded that CPAP studies have consistently failed to show improvements in non-sleep related outcomes linked with OSA, such as stroke, heart attack, diabetes, and depression. The AHRQ report concluded that the evidence published to date "mostly does not support that CPAP prescription affects long-term, clinically important outcomes."

In an email to MedPage Today, Azarbarzin noted that AHRQ researchers identified the reliance on apnea hypoxia index (AHI) to measure OSA severity in randomized clinical trials as a possible reason for the null CPAP findings.

"AHI is the number of apneas (complete airway obstruction) and hypopneas (partial airway obstruction that leads to a drop in oxygen or arousal from sleep) per hour of sleep, and by definition has many limitations, and fails to capture different subtypes of OSA," he explained. "We believe additional measurements, such as heart rate surge in response to events, are critical in capturing the heterogeneity in OSA and identifying those who benefit most from CPAP."

He noted that while randomized trials in patients with coronary artery disease (CAD) and non-sleepy OSA have failed to show a benefit for CPAP in preventing heart attack and stroke, his own group's recently published research suggests an elevated risk for heart attack and stroke in heart patients with OSA without daytime sleepiness who demonstrate greater respiratory-related pulse rate response during OSA events.

Based on these findings, Azarbarzin and colleagues hypothesized that patients with higher respiratory-event-related pulse rate response would benefit from CPAP in terms of lower CV risk.

"If this were true, then we would expect to see a preferential benefit from using CPAP on cardiac outcomes in those with the higher pulse rate response," Azarbarzin said in a press statement. "Indeed, this is what we found: the greater the pulse rate response, the greater the calculated treatment benefit of CPAP."

Respiratory-event-related pulse rate response (ΔHR) was measured from the oximetry pulse rate signals collected during baseline polysomnography among participants in the RICCADSA trial, which was designed to examine the impact of positive airway pressure therapy on CV risk in heart patients with non-sleepy OSA.

The researchers used multivariable Cox regression to assess whether the effect of autotitrating CPAP treatment on CV events was moderated by ΔHR per significant interaction.

Primary models included covariates (age, sex, BMI, and revascularization type) to maximize model precision. Secondary analysis examined ΔHR responsiveness by normalizing against event severity measures (desaturation area, arousal intensity, event duration). Sensitivity analysis excluded patients who were not on beta-blockers.

The analysis included patients with CAD and OSA (AHI ≥15/h) randomized to treatment with CPAP (n=122) or no CPAP (n=122), with a median follow-up of 57 months.

Respiratory-event-related pulse rate response measures were obtained in 92% of patients (mean 7.1 BPM) and a total of 48 composite events over a 57-month median follow-up were recorded.

A significant interaction was observed between CPAP treatment and respiratory-event-related pulse rate response (interaction HR 0.51, 95% CI 0.26-0.98, P=0.043).

At elevated ΔHR (10.8 BPM), the treatment HR was 0.39 (95% CI 0.15-0.98) in contrast to no significant effect at normal ΔHR (7.1 BPM, HR 0.76, 95% CI 0.42-1.37, P=0.4).

Normalized ΔHR measures were stronger determinants of treatment-related risk reduction:

• Desaturation area: interaction HR 0.45 (95% CI 0.23-0.87)
• Arousal intensity: interaction HR 0.30 (95% CI 0.12-0.75)
• Event duration: interaction HR 0.45 (95% CI 0.23-0.87)

The exclusion of patients not using beta-blockers yielded similar findings.

"This study provides novel evidence that a greater heart rate response to respiratory events is a risk factor that was identifiable, deleterious, and potentially reversible and could be used to select patients most likely to benefit from CPAP therapy," Azarbarzin said.