Loop Gain as a Predictor of Blood Pressure Response in Patients Treated for Obstructive Sleep Apnea.

Rationale: Randomized trials have shown inconsistent cardiovascular benefits from obstructive sleep apnea (OSA) therapy. Intermittent hypoxemia can increase both sympathetic nerve activity and loop gain ("ventilatory instability"), which may thus herald cardiovascular treatment benefit. Objectives: Test the hypothesis that loop gain predicts changes in 24h-mean blood pressure (Δ24h-MBP) in response to OSA therapy and compare its predictive value against other novel biomarkers. Methods: The HeartBEAT trial assessed the effect of 12 weeks of continuous positive airway pressure (CPAP) vs oxygen vs control on 24h-MBP. We measured loop gain and hypoxic burden from sleep tests and identified subjects with a sleepy phenotype using cluster analysis. Associations between biomarkers and 24h-MBP were assessed in the CPAP/oxygen arms using linear regression models adjusting for various covariates. Secondary outcomes and predictors were analyzed similarly. Results: We included 93 and 94 participants in the CPAP and oxygen arm, respectively. Overall, changes in 24h-MBP were small, but inter-individual variability was substantial (mean (SD) -2 (8) and 1 (8) mmHg in the CPAP and oxygen arm, respectively). Higher loop gain was significantly associated with greater reductions in 24h-MBP independent of covariates in the CPAP arm (-1.5 to -1.9 mmHg per 1-SD-increase in loop gain, P≤0.03), but not in the oxygen arm. Other biomarkers were not associated with improved cardiovascular outcomes. Conclusions: To our knowledge, this is the first study suggesting that loop gain predicts blood pressure response to CPAP therapy. Eventually, loop gain estimates may facilitate patient selection for research and clinical practice. Clinical Trial Registration: NCT01086800.