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Association of Hypoxic Burden With Cardiovascular Events: A Risk Stratification Analysis of the Randomized
Yüksel Peker1, Yeliz Celik2, Andrey Zinchuk3
1Department of Pulmonary Medicine, Koc University School of Medicine, and Koc University Research Center for Translational Medicine, Istanbul, Türkiye; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital & Harvard Medical School, Boston, MA; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Sciences, Respiratory Medicine and Allergology, Faculty of Medicine, Lund University, Lund, Sweden.
Background:
The apnea-hypopnea index (AHI), the standard measure of OSA, has limitations in reflecting disease severity.
Research Question:
Is high hypoxic burden (HB) more strongly associated with major cardiovascular and cerebrovascular adverse events (MACCEs) than AHI of ≥ 30 events/h?
Study Design And Methods:
This secondary analysis of the Randomized Intervention With CPAP in Coronary Artery Disease and Sleep Apnea observational cohort included 368 adults with OSA (AHI ≥ 15 events/h) with (n = 155) and without (n = 244) excessive daytime sleepiness (EDS), defined as an Epworth Sleepiness Scale score of ≥ 10. HB was calculated as the total area under respiratory event-related desaturations divided by total sleep time. Patients were classified as having high or low HB based on the median (60.7%min/h). The primary outcome was the incident of the first MACCE. Cox proportional hazard models assessed associations in the full cohort and by CPAP allocation and adherence (nonadherent or no positive airway pressure [PAP] group, n = 262; adherent [adjusted PAP use ≥ 4 h/night for all nights at 1-year follow-up], n = 106). In an exploratory analysis, participants were grouped into 4 categories based on median AHI and HB (low and low, low and high, high and low, and high and high, respectively).
Results:
Over a median follow-up of 4.7 years, high HB was associated with MACCEs (adjusted hazard ratio, 1.87; 95% CI, 1.17-2.98; P = .009), particularly among untreated or nonadherent patients and those with baseline EDS. AHI of ≥ 30 events/h was not associated significantly with MACCEs (P = .366). When modelled continuously, HB and AHI each were associated with MACCEs; however, compared with low AHI and low HB, only high HB, regardless of AHI level, was linked to increased risk. In contrast, high AHI and low HB was not associated with MACCEs.
Interpretation:
High HB, but not AHI of ≥ 30 events/h, was associated with MACCEs in adults with moderate to severe OSA. Although AHI was associated with outcomes when modelled continuously, elevated risk seemed to be driven primarily by high HB.
Clinical Trial Registration:
ClinicalTrials.gov; No.: NCT00519597; URL: www.
Clinicaltrials:
gov.
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