Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness
Ali Azarbarzin, Andrey Zinchuk, Andrew Wellman, Gonzalo Labarca, Daniel Vena, L. Gell, Ludovico Messineo, David P. White, Daniel J. Gottlieb, Susan Redline, Yüksel Peker, Scott A. Sands
Abstract
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.