Heart rate response to sleep apnea events may aid in determining CV benefit from CPAP

CPAP therapy may have a protective effect on adverse cardiovascular outcomes in patients with coronary artery disease and nonsleepy obstructive sleep apnea who have greater heart rate responses to sleep apnea events.

Greater heart rate response to respiratory events “could be used to select patients most likely to exhibit long-term cardiovascular benefit from CPAP therapy,” Ali Azarbarzin, PhD, with the division of sleep and circadian disorders at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, said during a presentation at the virtual American Thoracic Society International Conference.

Previous randomized controlled trials have not detected a protective effect of CPAP therapy on CV outcomes in this patient population, according to the researchers. However, recent analysis of large cohort studies showed that a subgroup of patients with nonsleepy OSA and greater respiratory event-related heart rate response had increased risk for CV events, Azarbarzin said.

Azarbarzin and colleagues reanalyzed data from the RICCADSA trial of CV risk in patients with nonsleepy OSA and coronary artery disease. The researchers determined participants’ heart rates and tested the hypothesis that patients with higher heart rate responses to apneas and hypopneas would have the greatest CV event 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 release. “Indeed, this is what we found: the greater the pulse rate response, the greater the calculated treatment benefit of CPAP.”

The analysis involved 244 patients with nonsleepy OSA (apnea-hypopnea index 15/hour) who were randomly assigned to CPAP therapy or no CPAP therapy and followed for a median of 57 months. Most participants were men, the mean age was 66 years and the majority were on beta-blockers.

Heart rate was measured by pulse oximetry during polysomnography during the RICCADSA trial. Researchers matched patients’ heart rates with whether they had CV or cerebrovascular events while experiencing apnea or hypopnea. They then used statistical methods to assess whether changes in heart rate influenced the protective effect of CPAP therapy.

In the overall RICCADSA trial, CPAP therapy was not associated with a significant difference in the primary endpoint of first event of repeat revascularization, myocardial infarction, stroke or CV mortality compared with no CPAP (HR = 0.79; 95% CI, 0.45-1.41; P = .435).

In the current analysis, the researchers found that change in heart rate differentially modified the effect of OSA on CVD. Each standard deviation increase in respiratory event-related heart rate response, or HR, was associated with greater CVD risk (HR = 1.45; 95% CI, 1.04-2.02; P = .029). Further, with each standard deviation decrease in HR, the researchers observed that CPAP therapy lowered risk for CVD events (HR = 0.54; 95% CI, 0.3-0.98; P = .043), Azarbarzin said during the presentation.

“When you look at those with high HR, the HR risk reduction was significantly larger — actually, more than 50% reduction in risk with CPAP treatment,” he said.

Among those with a high HR (10 bpm), the HR for CVD was 0.7 for CPAP therapy and 1.6 for no CPAP, he said. Among those with a low HR (4 bpm), the HR for CVD was 1.2 for CPAP therapy and 0.8 for no CPAP. Among those with the mean HR (7 bpm), the HR for CVD was 0.9 for CPAP therapy and 1.1 for no CPAP.

“This study provides novel evidence that a greater heart rate response to respiratory events is a risk factor that is identifiable, deleterious and potentially reversible,” Azarbarzin said.

References:

• Azarbarzin A, et al. Am J Respir Crit Care Med. 2021;doi:10.1164/ajrccm-conference.2021.203.1.
• Press Release.