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CPAP Protects Against Cardiac Events in Non-sleepy Obstructive Sleep Apnea

Presenter: Ali Azarbarzin, PhD

An elevated pulse rate in heart patients with non-sleepy obstructive sleep apnea may lead to serious cardiac events, but continuous positive airway pressure (CPAP) therapy provides protection against adverse cardiovascular outcomes.

Previous studies have shown no benefit of CPAP for non-sleepy OSA patients who do not report daytime sleepiness. These patients have approximately the same number of apneas and hypopneas shown on polysomnography as those patients who report daytime sleepiness. A recent analysis of large cohort studies revealed that a subgroup of patients with non-sleepy OSA who demonstrated a greater respiratory-event-related pulse rate response (ΔHR) were at increased risk of cardiovascular morbidity and mortality.

Researchers led by Ali Azarbarzin, PhD, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, assistant professor of medicine, Harvard Medical School, tested the hypothesis that a larger pre-treatment ΔHR was associated with greater CPAP-related reduction in adverse cardiovascular outcomes in patients with coronary artery disease and non-sleepy OSA. They did so by re-analyzing data from the RICCADSA clinical trial of cardiovascular risk for non-sleepy OSA patients with heart disease.

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

The researchers examined pulse rate as measured by pulse oximetry during polysomnography for those participating in the randomized controlled RICCADSA trial with non-sleepy OSA. The RICCADSA trial included 112 CPAP patients and 113 control patients; most of the patients were male (86%), with a mean age of 67 years. Then they matched patients’ pulse rates with whether they had cardiovascular or cerebrovascular events, such as myocardial infarction, stroke, and cardiovascular mortality, while experiencing apnea or hypopnea. Next, they used multivariable cox regression analysis to assess whether changes in pulse rate influenced the protective effect of CPAP treatment.

∆HR measures were obtained in 92% of patients, and 48 composite events over a 57-month median follow-up were recorded. The researchers found that CPAP provided protection from cardiac events in those non-sleepy OSA patients whose pulse rates rose significantly during sleep apnea events.

They observed a significant interaction between treatment and ∆HR, with an interaction hazard ratio of 0.51. At elevated ∆HR, the treatment hazard ratio was 0.39 in contrast to no significant effect at normal ∆HR (hazard ratio 0.76). Normalized ∆HR measures were stronger determinants of treatment-related risk reduction, arousal intensity, and event duration. “Treatment benefit is associated with greater normalized ∆HR (responsiveness) rather than just event severity,” said Azarbarzin.

In conclusion, Azarbarzin said: “Our study provides novel evidence that greater heart rate responsiveness to obstructive events is an identifiable, deleterious and potentially reversible risk factor that could be used to select patients most likely to exhibit long-term cardiovascular benefit from CPAP therapy.”

Some patients have a major surge in their pulse rate at the end of these events, while others barely increase their pulse rate. Azarbarzin said that, intuitively, these groups may have different cardiovascular outcomes. “Our study suggests that there is, in fact, a subgroup of non-sleepy patients with OSA for whom CPAP could provide a reduction in risk—those with a higher pulse rate response to their respiratory events,” said Azarbarzin.

Link to abstract: Cardiovascular Benefit of CPAP Is Modified by the Sleep Apnea Related Pulse Rate Response in Coronary Artery Disease Patients with Nonsleepy OSA: Findings from the RICCADSA Randomized Controlled Trial

Ali Azarbarzin, PhD

Consulting: Somnifix, Apnimed

Grants: American Heart Association, National Institute of Health, American Academy of Sleep Medicine Foundation, Somnifix

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