Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness

Abstract

Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR). Objectives: Here, in this post hoc analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment ΔHR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. Methods: ΔHR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index ⩾ 15 events/h] with Epworth Sleepiness Scale score < 10; n_CPAP:n_control = 113:113; male, 85%; age, 66 ± 8 [mean ± SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by ΔHR (treatment-by-ΔHR interaction). Measurements and Main Results: The CPAP-related reduction in risk increased progressively with increasing pretreatment ΔHR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in ΔHR; P < 0.05). This means that in patients with a ΔHR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) (P < 0.05), but no significant risk reduction was estimated in patients with a mean ΔHR (6 beats/min; CPAP risk reduction, 16% [-53% to 54%]; P = 0.6). Conclusions: The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the ΔHR. Specifically, patients with higher ΔHR exhibit greater cardiovascular benefit from CPAP therapy.

Keywords: cardiovascular; clinical trial; heart rate response; sleep apnea; sleepiness.

Figure 1.

Flow diagram presenting ascertainment of the study sample. CPAP = continuous positive airway pressure; PSG = polysomnography.

Figure 2.

The pulse rate response to each individual respiratory event (ΔHR) was defined as the maximum pulse rate during a subject-specific search window (see Figure E1 for more detail) and the minimum pulse rate during that event. The individual-level ΔHR was defined as the mean of all event-specific responses. BPM = beats per minute.

Figure 3.

Unadjusted Kaplan-Meier survival curve demonstrates a preferential benefit of continuous positive airway pressure (CPAP) in those with high pulse rate response to respiratory events (ΔHR; ΔHR ⩾ 6 BPM). No significant effect was observed in all comers. There was a suggestion of possible harm from CPAP in those with a low ΔHR (ΔHR < 6 BPM). BPM = beats per minute; CVD = cardiovascular disease; ΔHR = pulse rate response to respiratory events.