Dominik Linz1, Kelly A Loffler2, Prashanthan Sanders3, Peter Catcheside2, Craig S Anderson4, Danni Zheng5, WeiWei Quan6, Mary Barnes7, Susan Redline8, R Doug McEvoy9, Mathias Baumert10. 1. Heart Rhythm Disorders (CHRD), South Australian Health and Medical Research Institute (SAHMRI), University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia; Department of Cardiology, Maastricht University Medical Centre, Maastricht, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, The Netherlands; Department of Cardiology, Radboud University Medical Centre, Nijmegen, The Netherlands. Electronic address: dominik.linz@mumc.nl. 2. Adelaide Institute for Sleep Health (AISH), College of Medicine and Public Health, Flinders University, Adelaide, Australia. 3. Heart Rhythm Disorders (CHRD), South Australian Health and Medical Research Institute (SAHMRI), University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia. 4. George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Neurology Department, Royal Prince Alfred Hospital, Sydney, NSW, Australia. 5. George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. 6. George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Department of Cardiology, Rui Jin Hospital and Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 7. Flinders Centre for Epidemiology and Biostatistics, Flinders University, Adelaide, Australia. 8. Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 9. Adelaide Institute for Sleep Health (AISH), College of Medicine and Public Health, Flinders University, Adelaide, Australia; Sleep Health Service, Respiratory and Sleep Services, Southern Adelaide Local Health Network, Adelaide, Australia. 10. School of Electrical and Electronic Engineering, University of Adelaide, Adelaide, Australia.
Abstract
BACKGROUND: Traditional methods for the quantification of OSA severity may not encapsulate potential relationships between hypoxemia in OSA and cardiovascular risk. RESEARCH QUESTION: Do novel nocturnal oxygen saturation (Spo2) metrics have prognostic value in patients with OSA and high cardiovascular event risk? STUDY DESIGN AND METHODS: We conducted post hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. In 2687 individuals, Cox proportional hazards models that were stratified for treatment allocation were used to determine the associations between clinical characteristics, pulse oximetry-derived metrics that were designed to quantify sustained and episodic features of hypoxemia, and cardiovascular outcomes. Metrics included oxygen desaturation index, time <90% Spo2, average Spo2 for the entire recording (mean Spo2), average Spo2 during desaturation events (desaturation Spo2), average baseline Spo2 interpolated across episodic desaturation events (baseline Spo2), episodic desaturation event duration and desaturation/resaturation-time ratio, and mean and SD of pulse rate. RESULTS: Neither apnea-hypopnea index, oxygen desaturation index, nor any of the novel Spo2 metrics were associated with the primary SAVE composite cardiovascular outcome. Mean and baseline Spo2 were associated with heart failure (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .009; and HR, 0.78; 95% CI, 0.67-0.90; P = .001, respectively) and myocardial infarction (HR, 0.86; 95% CI, 0.77-0.95; P = .003; and HR, 0.81; 95% CI, 0.73-0.90; P < .001, respectively). Desaturation duration and desaturation/resaturation time ratio, with established risk factors, predicted future heart failure (area under the curve, 0.86; 95% CI, 0.79-0.93). INTERPRETATION:Apnea-hypopnea index and oxygen desaturation index were not associated with cardiovascular outcomes. In contrast, the pattern of oxygen desaturation was associated with heart failure and myocardial infarction. However, concomitant risk factors remained the predominant determinants for secondary cardiovascular events and thus deserve the most intensive management.
RCT Entities:
BACKGROUND: Traditional methods for the quantification of OSA severity may not encapsulate potential relationships between hypoxemia in OSA and cardiovascular risk. RESEARCH QUESTION: Do novel nocturnal oxygen saturation (Spo2) metrics have prognostic value in patients with OSA and high cardiovascular event risk? STUDY DESIGN AND METHODS: We conducted post hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. In 2687 individuals, Cox proportional hazards models that were stratified for treatment allocation were used to determine the associations between clinical characteristics, pulse oximetry-derived metrics that were designed to quantify sustained and episodic features of hypoxemia, and cardiovascular outcomes. Metrics included oxygen desaturation index, time <90% Spo2, average Spo2 for the entire recording (mean Spo2), average Spo2 during desaturation events (desaturation Spo2), average baseline Spo2 interpolated across episodic desaturation events (baseline Spo2), episodic desaturation event duration and desaturation/resaturation-time ratio, and mean and SD of pulse rate. RESULTS: Neither apnea-hypopnea index, oxygen desaturation index, nor any of the novel Spo2 metrics were associated with the primary SAVE composite cardiovascular outcome. Mean and baseline Spo2 were associated with heart failure (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .009; and HR, 0.78; 95% CI, 0.67-0.90; P = .001, respectively) and myocardial infarction (HR, 0.86; 95% CI, 0.77-0.95; P = .003; and HR, 0.81; 95% CI, 0.73-0.90; P < .001, respectively). Desaturation duration and desaturation/resaturation time ratio, with established risk factors, predicted future heart failure (area under the curve, 0.86; 95% CI, 0.79-0.93). INTERPRETATION: Apnea-hypopnea index and oxygen desaturation index were not associated with cardiovascular outcomes. In contrast, the pattern of oxygen desaturation was associated with heart failure and myocardial infarction. However, concomitant risk factors remained the predominant determinants for secondary cardiovascular events and thus deserve the most intensive management.
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